Clinical Studies

Abstracts are presented below for clinical studies on Turmeric.

  • Botanical Name: Curcuma Longa

  • Ayurvedic Name: Haridra

  • Common Name: Turmeric

Curcuma Longa

Plant Phytonutrient Profile


1: J Ethnobiol Ethnomedicine. 2007 Feb 26;3(1):11 [Epub ahead of print]

Ethnoveterinary medicines used for ruminants in British Columbia, Canada.

Lans C, Turner N, Khan T, Brauer G, Boepple W.

ABSTRACT: BACKGROUND: The use of medicinal plants is an option for livestock
farmers who are not allowed to use allopathic drugs under certified organic
programs or cannot afford to use allopathic drugs for minor health problems of
livestock. METHODS: In 2003 we conducted semi-structured interviews with 60
participants obtained using a purposive sample. Medicinal plants are used to
treat a range of conditions. A draft manual prepared from the data was then
evaluated by participants at a participatory workshop. RESULTS: There are 128
plants used for ruminant health and diets, representing several plant families.
The following plants are used for abscesses: Berberis aquifolium / Mahonia
aquifolium Echinacea purpurea, Symphytum officinale, Bovista pila, Bovista
plumbea, Achillea millefolium and Usnea longissima. Curcuma longa L., Salix
scouleriana and Salix lucida are used for caprine arthritis and caprine
arthritis encephalitis. Euphrasia officinalis and Matricaria chamomilla are used
for eye problems. Wounds and injuries are treated with Bovista spp., Usnea
longissima, Calendula officinalis, Arnica sp., Malva sp., Prunella vulgaris,
Echinacea purpurea, Berberis aquifolium / Mahonia aquifolium, Achillea
millefolium, Capsella bursa-pastoris, Hypericum perforatum, Lavandula
officinalis, Symphytum officinale and Curcuma longa. Syzygium aromaticum and
Pseudotsuga menziesii are used for coccidiosis. The following plants are used
for diarrhea and scours: Plantago major, Calendula officinalis, Urtica dioica,
Symphytum officinale, Pinus ponderosa, Potentilla pacifica, Althaea officinalis,
Anethum graveolens, Salix alba and Ulmus fulva. Mastitis is treated with
Achillea millefolium, Arctium lappa, Salix alba, Teucrium scorodonia and Galium
aparine. Anethum graveolens and Rubus sp., are given for increased milk
production. Taraxacum officinale, Zea mays, and Symphytum officinale are used
for udder edema. Ketosis is treated with Gaultheria shallon, Vaccinium sp., and
Symphytum officinale. Hedera helix and Alchemilla vulgaris are fed for retained
placenta. CONCLUSIONS: Some of the plants showing high levels of validity were
Hedera helix for retained placenta and Euphrasia officinalis for eye problems.
Plants with high validity for wounds and injuries included Hypericum perforatum,
Malva parviflora and Prunella vulgaris. Treatments with high validity against
endoparasites included those with Juniperus communis and Pinus ponderosa.
Anxiety and pain are well treated with Melissa officinalis and Nepeta caesarea.

PMID: 17324258 [PubMed - as supplied by publisher]

2: J Nat Prod. 2007 Feb;70(2):143-6.

NMR study of the solution structure of curcumin.

Payton F, Sandusky P, Alworth WL.

Department of Chemistry and Coordinated Instrumentation Facility, Tulane
University, New Orleans, Louisiana 70118, and National Center for Natural
Products Research, University of Mississippi, University, Mississippi 38677.

Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is
derived from the rhizomes of Curcuma longa. Although early studies concluded
that curcumin exists predominantly as a keto-enol tautomer, 1b, in several
recent articles the solution structure of curcumin has been represented as a
beta-diketone tautomer, 1a. We have investigated the structure of curcumin in
solvents ranging in polarity from CDCl3 to mixtures of DMSO-d6 in water, and in
buffered aqueous DMSO-d6 solutions with pH values varying from 3 to 9. The
solution structure of curcumin was determined on the basis of NMR techniques,
including DEPT, HMQC, HMBC, and COSY. The results of the NMR studies show
definitely that curcumin exists in solution as keto-enol tautomers, 1b.

PMID: 17315954 [PubMed - in process]

3: Carcinogenesis. 2007 Feb 2; [Epub ahead of print]

Bax and Bak genes are essential for maximum apoptotic response by curcumin, a
polyphenolic compound and cancer chemopreventive agent derived from turmeric,
Curcuma longa.

Shankar S, Srivastava RK.

Department of Biochemistry, University of Texas Health Center at Tyler, Tyler,
Texas, USA 75703.

Curcumin, an active ingredient of turmeric (Curcuma longa), inhibits
proliferation and induces apoptosis in cancer cells, but the sequence of events
leading to cell death is poorly defined. The objective of this study was to
examine the molecular mechanisms by which multidomain proapoptotic Bcl-2 family
members Bax and Bak regulate curcumin-induced apoptosis using mouse embryonic
fibroblasts (MEFs) deficient in Bax, Bak or both genes. Curcumin treatment
resulted an increase in the protein levels of both Bax and Bak, and
mitochondrial translocation and activation of Bax in MEFs to trigger drop in
mitochondrial membrane potential, cytosolic release of apoptogenic molecules
(cytochrome c and Smac/DIABLO), activation of caspase-9 and caspase-3, and
ultimately apoptosis. Furthermore, MEFs derived from Bax and Bak double knockout
mice exhibited even greater protection against curcumin-induced release of
cytochrome c and Smac, activation of caspase-3 and caspase-9, and induction of
apoptosis compared with wild-type, or single knockout Bax(-/-) or Bak(-/-) MEFs.
Interestingly, curcumin treatment also caused an increase in the protein level
of Apaf-1 in wild-type MEFs. Smac N7 peptide enhanced curcumin-induced
apoptosis, whereas Smac siRNA inhibited the effects of curcumin on apoptosis.
Mature form of Smac sensitized Bax and Bak double knockout MEFs to undergo
apoptosis by acting downstream of mitochondria. The present study demonstrates
the role of Bax and Bak as a critical regulator of curcumin-induced apoptosis
and overexpression of Smac as interventional approaches to deal with Bax- and/or
Bak-deficient chemo-resistant cancers for curcumin-based therapy.

PMID: 17277231 [PubMed - as supplied by publisher]

4: Int Immunopharmacol. 2007 Mar;7(3):333-42. Epub 2006 Dec 18.

Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2
and iNOS expression in chronic experimental colitis.

Camacho-Barquero L, Villegas I, Sanchez-Calvo JM, Talero E, Sanchez-Fidalgo S,
Motilva V, Alarcon de la Lastra C.

Department of Pharmacology, School of Pharmacy, University of Seville, Profesor
Garcia Gonzalez Street, 2, 41012-Seville, Spain.

Ulcerative colitis (UC) is a nonspecific inflammatory disorder characterized by
oxidative and nitrosative stress, leucocyte infiltration and up-regulation of
pro-inflammatory cytokines. Mitogen-activated protein kinases (MAPKs), such as
the p38 and the c-Jun N-terminal kinase (JNK) modulate the transcription of many
genes involved in the inflammatory process. Curcumin is a polyphenol derived
from Curcuma longa, which is known to have anti-inflammatory activity. The aim
of this study was to study the effects and mechanisms of action of curcumin, on
chronic colitis in rats. Inflammation response was assessed by histology and
myeloperoxidase activity (MPO). We determined the production of Th1 and Th2
cytokines and nitrites in colon mucosa, as well as the expression of inducible
nitric oxide synthase (iNOS), cyclo-oxygenase(COX)-1 and-2 by western blotting
and inmmunohistochemistry. Finally, we studied the involvement of MAPKs
signaling in the protective effect of curcumin in chronic colonic inflammation.
Curcumin (50-100 mg/kg/day) were administered by oral gavage 24 h after
trinitrobenzensulfonic acid (TNBS) instillation, and daily during 2 weeks before
sacrifice. Curcumin significantly attenuated the damage and caused substantial
reductions of the rise in MPO activity and tumour necrosis factor alpha
(TNF)-alpha. Also curcumine was able to reduce nitrites colonic levels and
induced down-regulation of COX-2 and iNOS expression, and a reduction in the
activation of p38 MAPK; however, no changes in the activation of JNK could be
observed. In conclusion, we suggest that inhibition of p38 MAPK signaling by
curcumin could explain the reduced COX-2 and iNOS immunosignals and the nitrite
production in colonic mucosa reducing the development of chronic experimental
colitis.

PMID: 17276891 [PubMed - in process]

5: Int J Pharm. 2007 Jan 7; [Epub ahead of print]

Possible inhibitory mechanism of Curcuma drugs on CYP3A4 in 1alpha,25
dihydroxyvitamin D(3) treated Caco-2 cells.

Hou XL, Takahashi K, Kinoshita N, Qiu F, Tanaka K, Komatsu K, Takahashi K, Azuma
J.

Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of
Pharmaceutical Science, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871,
Japan.

Curcuma longa and C. zedoaria, belonging to genus Curcuma, have become prevalent
as supplements in East Asia. Curcumin is the most well-studied bioactive
component isolated from rhizomes of C. longa and other Curcuma species except C.
zedoaria. In this study, we investigated the affects of C. longa, C. zedoaria
from Japan and curcumin on CYP3A4. Caco-2 cells, in which CYP3A4 expression was
induced by 1alpha,25-(OH)(2)-D(3), were used to mimic the metabolism of small
intestine. Caco-2 cells were treated with methanol extracts from two Curcuma
rhizomes (0.1mg/ml) or curcumin (30muM) for 72h. Both extracts significantly
decreased the activity of CYP3A4 by about 85-98%. The 50% inhibitory
concentrations of C. longa and C. zedoaria extracts were 0.019 and 0.014mg/ml,
respectively. They caused a 60-70% decrease in CYP3A4 protein. Otherwise,
curcumin treatment caused a 30-40% decrease in CYP3A4 catalytic activity and a
38% decrease in CYP3A4 protein expression. Moreover, it was found that both
Curcuma extracts and curcumin treatment had no influence on CYP3A4 mRNA
expression. Our results suggested that administration of Curcuma drugs might
inhibit the catalytic activity of intestinal CYP3A4. However, curcumin was not
the major compound responsible for this inhibitory effect.

PMID: 17270371 [PubMed - as supplied by publisher]

6: Plant Foods Hum Nutr. 2007 Mar;62(1):25-9. Epub 2007 Jan 17.

Changes in Glycoprotein Components in Streptozotocin - Nicotinamide Induced Type
2 Diabetes: Influence of Tetrahydrocurcumin from Curcuma longa.

Pari L, Murugan P.

Department of Biochemistry, Faculty of Science, Annamalai University, Annamalai
Nagar 608 002, Tamil Nadu, India, [email protected]

Curcuma longa (Zingiberaceae) has been used traditionally as antidiabetic, and
has been proven scientifically to possess high antioxidant activity and
anticancer properties. The active components of Curcuma longa such as curcumin
and tetrahydrocurcumin (THC), a major colourless metabolite of curcumin also
possesses antidiabetic, antiinflammatory and antioxidant activity. The
ethnopharmacological value of this plant, the effect of THC on glycoproteins was
carried out in normal and streptozotocin-nicotiniamide induced type 2
hyperglycaemic rats for 45 days. Glucose, plasma insulin and glycoprotein
components in plasma and tissues (hexose, hexosamine, fucose and sialic acid)
were determined. Oral administration of THC to diabetic rats showed a decrease
in the level of blood glucose and plasma glycoproteins. The levels of plasma
insulin and tissue sialic acid were increased where as the levels of tissue
hexose, hexosamine and fucose were near normal in diabetic rats treated with
THC. The present study indicates that the THC possesses a significant beneficial
effect on glycoprotein moiety in addition to its antidiabetic effect. The effect
of THC is more prominent than curcumin.

PMID: 17226069 [PubMed - in process]

7: Basic Clin Pharmacol Toxicol. 2007 Jan;100(1):43-8.

Curcumin and kolaviron ameliorate di-n-butylphthalate-induced testicular damage
in rats.

Farombi EO, Abarikwu SO, Adedara IA, Oyeyemi MO.

Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry
College of Medicine, University of Ibadan, Ibadan, Nigeria.
[email protected]

The present study was carried out to evaluate the ameliorative effects of
kolaviron (a biflavonoid from the seeds of Garcinia kola) and curcumin (from the
rhizome, Curcuma longa L.) on the di-n-butylphthalate (DBP)-induced testicular
damage in rats. Administration of DBP to rats at a dose of 2 g/kg for 9 days
significantly decreased the relative testicular weights compared to the
controls, while the weights of other organs remained unaffected. Curcumin or
kolaviron did not affect all the organ weights of the animals. While only DBP
treatment significantly increased the testicular malondialdehyde level and
gamma-glutamyl transferase activity (gamma-GT), it markedly decreased
glutathione level, the testicular catalase, glucose-6-phosphate dehydrogenase,
superoxide dismutase, sperm gamma-GT activities and serum testosterone level
compared to the control group. Data on cauda epididymal sperm count and
live/dead ratio were not significantly affected in the DBP-treated rats. Alone,
DBP treatment resulted in a 66% decrease in spermatozoa motility and a 77%
increase in abnormal spermatozoa in comparison to control. DBP-treated rats
showed marked degeneration of the seminiferous tubules with necrosis and
defoliation of spermatocytes. The DBP-induced injuries in biochemical,
spermatological parameters and histological structure of testis were recovered
by treatment with kolaviron or curcumin. The pattern in the behaviour of these
compounds might be correlated with their structural variations. Our results
indicate that kolaviron and curcumin protect against testicular oxidative damage
induced by DBP. The chemoprotective effects of these compounds may be due to
their intrinsic antioxidant properties and as such may prove useful in combating
phthalate-induced reproductive toxicity.

PMID: 17214610 [PubMed - in process]

8: J Clin Immunol. 2007 Jan;27(1):19-35. Epub 2007 Jan 9.

"Spicing up" of the immune system by curcumin.

Jagetia GC, Aggarwal BB.

Cytokine Research Laboratory, Department of Experimental Therapeutics, The
University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.

Curcumin (diferuloylmethane) is an orange-yellow component of turmeric (Curcuma
longa), a spice often found in curry powder. Traditionally known for its an
antiinflammatory effects, curcumin has been shown in the last two decades to be
a potent immunomodulatory agent that can modulate the activation of T cells, B
cells, macrophages, neutrophils, natural killer cells, and dendritic cells.
Curcumin can also downregulate the expression of various proinflammatory
cytokines including TNF, IL-1, IL-2, IL-6, IL-8, IL-12, and chemokines, most
likely through inactivation of the transcription factor NF-kappaB.
Interestingly, however, curcumin at low doses can also enhance antibody
responses. This suggests that curcumin's reported beneficial effects in
arthritis, allergy, asthma, atherosclerosis, heart disease, Alzheimer's disease,
diabetes, and cancer might be due in part to its ability to modulate the immune
system. Together, these findings warrant further consideration of curcumin as a
therapy for immune disorders.

PMID: 17211725 [PubMed - in process]

9: Anticancer Res. 2006 Nov-Dec;26(6B):4379-89.

Curcumin-induced apoptosis of human colon cancer colo 205 cells through the
production of ROS, Ca2+ and the activation of caspase-3.

Su CC, Lin JG, Li TM, Chung JG, Yang JS, Ip SW, Lin WC, Chen GW.

School of Chinese Medicine, Department of Microbiology, China Medical
University, No 91, Hsueh-Shih Road, Taichung City 404, Taiwan, ROC.

Curcumin (diferuloylmethane), the yellow pigment in turmeric (Curcuma longa), is
known to inhibit proliferation of cancer cells by arresting them at various
phases of the cell cycle and to induce apoptosis in tumor cells.
Curcumin-induced apoptosis mainly involves the activation of caspase-3 and
mitochondria-mediated pathway in various cancer cells of different tissue
origin. In the present study, the induction of apoptosis and cytotoxicity by
curcumin in colon cancer colo 205 cells was investigated by using flow
cytometry. The results demonstrated that curcumin induced cytotoxicity and
apoptosis dose- and time-depedently. Curcumin induced the production of reactive
oxygen species (ROS) and Ca+2, decreased the levels of mitochondria membrane
potential and induced caspase-3 activity. Curcumin also promoted the expression
of Bax, cytochrome C, p53 and p21 but inhibited the expression of Bcl-2. These
observations suggest that curcumin may have a possible therapeutic potential in
colon cancer patients.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17201158 [PubMed - indexed for MEDLINE]

10: Anticancer Res. 2006 Nov-Dec;26(6B):4361-71.

Curcumin-induced cell cycle arrest and apoptosis in human acute promyelocytic
leukemia HL-60 cells via MMP changes and caspase-3 activation.

Tan TW, Tsai HR, Lu HF, Lin HL, Tsou MF, Lin YT, Tsai HY, Chen YF, Chung JG.

Department of Pharmacology, China Medical University, Taichung 404, ROC.

Curcumin (diferuloylmethane), is a natural product derived from the root of the
plant Curcuma longa. For centuries, it has been used as a spice and as a herbal
medicine in Chinese populations. Curcumin has been shown to inhibit cell
proliferation, cell cycle arrest, cyclooxygenase (COX)-1 and -2 expression and
apoptosis in several human cancer cell lines. The aim of this investigation was
to clarify the mechanisms by which curcumin induced cytotoxicity and apoptosis
in human leukemia HL-60 cells. The effects of curcumin on the levels of reactive
oxygen species (ROS), Ca+2 production, cyclin E, cdc25c, wee1, Bcl-2, Bax, the
changes of mitochondrial membrane potential (MMP), cytochrome c release and the
activation of caspase-3 were also investigated in the HL-60 cells. Results of
flow cytometry and DAPI staining assays indicated that curcumin induced
cytotoxicity and apoptosis in the examined cells. The results from flow
cytometry assay indicated that curcumin induced ROS and Ca+2 productions,
decreased the levels of MMP and increased the activity of caspase-3, leading to
cell apoptosis. Western blot assay also revealed that curcumin increased the
levels of Bax and the release of cytochrome c, and decreased the levels of Bcl-2
in the examined cells. The inhibition of caspase-3 activation by z-VAD-fmk
(broad-spectrum caspase inhibitor) completely blocked curcumin-induced apoptosis
in HL-60 cells.

PMID: 17201156 [PubMed - indexed for MEDLINE]

11: J Immunol. 2007 Jan 1;178(1):111-21.

Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B
lymphoma growth.

Gururajan M, Dasu T, Shahidain S, Jennings CD, Robertson DA, Rangnekar VM,
Bondada S.

Department of Microbiology, Immunology, and Molecular Genetics, University of
Kentucky, Lexington, KY 40536, USA.

Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma
longa), has been shown in recent studies to have therapeutic potential in the
treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the
ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited
the growth of both murine and human B lymphoma in vitro and murine B lymphoma in
vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma
is through inhibition of the survival kinase Akt and its key target Bad.
However, in vitro kinase assays show that Akt is not a direct target of
curcumin. We identified a novel target for curcumin in B lymphoma viz spleen
tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B
lymphoma cell lines and curcumin down-modulates Syk activity accompanied by
down-regulation of Akt activation. Moreover, we show that overexpression of Akt,
a target of Syk, or Bcl-x(L), a target of Akt can overcome curcumin-induced
apoptosis of B lymphoma cells. These observations suggest a novel growth
promoting role for Syk in lymphoma cells.

Publication Types:
Research Support, N.I.H., Extramural

PMID: 17182546 [PubMed - in process]

12: Gynecol Oncol. 2006 Dec 14; [Epub ahead of print]

Curcumin enhances Apo2L/TRAIL-induced apoptosis in chemoresistant ovarian cancer
cells.

Wahl H, Tan L, Griffith K, Choi M, Liu JR.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology,
University of Michigan, 4219 CCGC, 1500 East Medical Center Drive, Ann Arbor, MI
48128, USA.

OBJECTIVE.: Curcumin, the active component of turmeric (Curcuma longa), exhibits
growth inhibitory activity against prostate, colon, and breast cancer; however,
the effect of curcumin on ovarian cancer cells is not known. We hypothesized
that curcumin could induce cell death in ovarian cancer cells, and enhance
apoptosis induced by tumor necrosis factor-related apoptosis inducing Apo2
ligand/TRAIL. METHODS.: Chemoresistant ovarian cancer cell lines SKOV3 and ES-2
were used. The cytotoxic effect of curcumin, Apo2L/TRAIL, and
curcumin+Apo2L/TRAIL in combination was determined by sulforhodamine assay.
Apoptotic fraction was determined by staining cells with propidium iodide
followed by analysis of the sub-G(0) DNA content of cells by flow cytometry.
Caspase activation was determined by immunoblotting. RESULTS.: Curcumin alone
had a cytotoxic effect in cisplatin-resistant cells at 25 muM. Curcumin at low
doses (5-15 muM) or Apo2L/TRAIL alone was not significantly cytotoxic to the
cell lines tested. Preincubating cells with curcumin at low doses prior to
treating with Apo2L/TRAIL resulted in markedly enhanced cell death. The combined
treatment of curcumin and Apo2L/TRAIL resulted in activation of both the
extrinsic, receptor-mediated apoptotic pathway (cleavage of caspase-8) and the
intrinsic, mitochondria-mediated apoptotic pathway (cleavage of caspase-9).
CONCLUSIONS.: Combined curcumin and Apo2L/TRAIL treatment results in enhanced
induction of apoptotic cell death. Because curcumin and Apo2L/TRAIL together can
activate both the extrinsic and intrinsic pathways of apoptosis, they may
circumvent chemoresistance to conventional chemotherapeutic agents.

PMID: 17174384 [PubMed - as supplied by publisher]

13: Dermatitis. 2006 Dec;17(4):196-7.

Contact urticaria from curcumin.

Liddle M, Hull C, Liu C, Powell D.

Department of Dermatology, University of Utah School of Medicine, Salt Lake
City, UT 84132, USA.

Turmeric, a spice derived from the rhizome of the plant Curcuma longa, contains
the chemical curcumin, which is responsible for turmeric's taste, color, and
biologic properties. Curcumin is used as a spice in foods, as a treatment in
traditional medicine, as a dye for fur, and as a component in nutritional
supplements. A few cases of allergic contact dermatitis from curcumin have been
reported. We report two cases of contact urticaria from curcumin. These cases
are mediated by two different mechanisms of contact urticaria: nonimmunologic
and immunologic (immunoglobulin-E mediated).

PMID: 17150169 [PubMed - in process]

14: J Agric Food Chem. 2006 Dec 13;54(25):9573-83.

Metabolic profiling of turmeric (Curcuma longa L.) plants derived from in vitro
micropropagation and conventional greenhouse cultivation.

Ma X, Gang DR.

Department of Plant Sciences and BIO5 Institute, 303 Forbes Building, The
University of Arizona, Tucson, AZ 85721-0036, USA.

Turmeric (Curcuma longa) was considered only a culinary spice in many parts of
the world until the notable anti-inflammation curcuminoids were discovered from
this herb. Because it is a sterile triploid and is propagated vegetatively by
rhizome division, turmeric is susceptible to pathogens that accumulate and are
transmitted from generation to generation, and amplification of particularly
useful stocks is a slow process. An in vitro propagation method has been
developed to alleviate these problems. Metabolic profiling, using GC-MS and
LC-ESI-MS, was used to determine if chemical differences existed between
greenhouse-grown and in vitro micropropagation derived plants. The major
chemical constituent curcuminoids, a group of diarylheptanoid compounds, as well
as major mono- and sesquiterpenoids were identified and quantified. Principal
component analysis and hierarchical cluster analysis revealed chemical
differences between lines (T3C turmeric vs Hawaiian red turmeric) and tissues
(rhizome, root, leaf, and shoot). However, this analysis indicated that no
significant differences existed between growth treatments (conventional
greenhouse-grown vs in vitro propagation derived plants).

Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17147448 [PubMed - in process]

15: J Ethnopharmacol. 2007 Mar 21;110(2):356-63. Epub 2006 Oct 17.

Behavioral, neurochemical and neuroendocrine effects of the ethanolic extract
from Curcuma longa L. in the mouse forced swimming test.

Xia X, Cheng G, Pan Y, Xia ZH, Kong LD.

State Key Laboratory of Pharmaceutical Biotechnology, Institute of Functional
Biomolecule, School of Life Sciences, Nanjing University, Nanjing 210093, PR
China.

Curcuma longa L. (turmeric) has been used for centuries in traditional Chinese
medicine as a treatment for mental disorders including depression. The studies
described here were undertaken to determine the behavioral, neurochemical and
neuroendocrine effects of the ethanolic extract from Curcuma longa using the
forced swimming test (FST) in male ICR strain of mice. The ethanolic extract was
found to reduce the duration of immobility in the mouse FST when orally
administered for 21 days. The extract markedly attenuated swim stress-induced
decreases in serotonin, 5-hydroxyindoleacetic acid, noradrenaline and dopamine
concentrations, as well as increases in serotonin turnover. Furthermore, the
ethanolic extract of Curcuma longa significantly reversed the swim
stress-induced increases in serum corticotropin-releasing factor and cortisol
levels. Under these conditions, the ethanolic extract of Curcuma longa was
partly different from fluoxetine and amitriptyline. These results suggested that
antidepressant properties of the ethanolic extract of Curcuma longa was mediated
through regulations of neurochemical and neuroendocrine systems and it may be a
useful agent against depression.

PMID: 17134862 [PubMed - in process]

16: J Agric Food Chem. 2006 Nov 29;54(24):9055-62.

Effects of ingested turmeric oleoresin on glucose and lipid metabolisms in obese
diabetic mice: a DNA microarray study.

Honda S, Aoki F, Tanaka H, Kishida H, Nishiyama T, Okada S, Matsumoto I, Abe K,
Mae T.

Research & Development Group, Functional Food Ingredients Division, and Life
Science Research Laboratories, Life Science RD Center, Kaneka Corporation,
Takasago, Hyogo 676-8688, Japan.

Turmeric, the rhizome of Curcuma longa L., has a wide range of effects on human
health. Turmeric oleoresin, an extract of turmeric, is often used for flavoring
and coloring. Curcuminoids and turmeric essential oil are both contained in
turmeric oleoresin, and both of these fractions have hypoglycemic effects. In
the present study, we comprehensively assessed the effect of turmeric oleoresin
on hepatic gene expression in obese diabetic KK-Ay mice using DNA microarray
analysis and quantitative real-time polymerase chain reaction (PCR). Female
KK-Ay mice aged 6 weeks (n = 6/group) were fed a high-fat diet containing
turmeric oleoresin, curcuminoids, and essential oil for 5 weeks. The same diet
without any of these fractions was used as a control diet. Ingestion of turmeric
oleoresin and essential oil inhibited the development of increased blood glucose
and abdominal fat mass, while curcuminoids only inhibited the increase in blood
glucose. DNA microarray analysis indicated that turmeric oleoresin ingestion
up-regulated the expression of genes related to glycolysis, beta-oxidation, and
cholesterol metabolism in the liver of KK-Ay mice, while expression of
gluconeogenesis-related genes was down-regulated. Real-time PCR analysis was
conducted to assess the contribution of the curcuminoids and essential oil in
turmeric oleoresin to the changes in expression of representative genes selected
by DNA microarray analysis. This analysis suggested that curcuminoids regulated
turmeric oleoresin ingestion-induced expression of glycolysis-related genes and
also that curcuminoids and turmeric essential oil acted synergistically to
regulate the peroxisomal beta-oxidation-related gene expression induced by
turmeric oleoresin ingestion. These changes in gene expression were considered
to be the mechanism by which the turmeric oleoresin affected the control of both
blood glucose levels and abdominal adipose tissue masses. All of these results
suggest that the use of whole turmeric oleoresin is more effective than the use
of either curcuminoids or the essential oil alone.

PMID: 17117790 [PubMed - indexed for MEDLINE]

17: J Ethnopharmacol. 2007 Mar 21;110(2):368-73. Epub 2006 Oct 13.

Curcumin/turmeric solubilized in sodium hydroxide inhibits HNE protein
modification-An in vitro study.

Kurien BT, Scofield RH.

Arthritis and Immunology Program, Oklahoma City, OK 73104, USA.

Free radical mediated lipid peroxidation has been implicated in multiple
diseases. A major oxidation by-product of this deleterious process is
4-hydroxy-2-nonenal (HNE). HNE is cytotoxic, mutagenic and genotoxic and is
involved in disease pathogenesis. Curcumin, a non-steroidal anti-inflammatory
agent (occurring as the yellow pigment found in the rhizomes of the perennial
herb Curcuma longa known as turmeric), has emerged as the newest "nutraceutical"
agent that has been shown to be efficacious against colon cancer and other
disorders, including correcting cystic fibrosis defects. Since curcumin has been
reported to have anti-oxidant properties we hypothesized that it will inhibit
HNE-modification of a protein substrate. Using an ELISA that employed
HNE-modification of solid phase antigen following immobilization, we found that
the curcumin solubilized in dilute alkali (5mM sodium hydroxide, pH 11)
inhibited HNE-protein modification by 65%. Turmeric also inhibited HNE-protein
modification similarly (65%) but at a much lower alkali level (130muM sodium
hydroxide, pH 7.6). Alkali by itself (5mM sodium hydroxide, pH 11) was found to
enhance HNE modification by as much as 267%. Curcumin/turmeric has to inhibit
this alkali enhanced HNE-modification prior to inhibiting the normal HNE protein
modification induced by HNE. Thus, inhibition of HNE-modification could be a
mechanism by which curcumin exerts its antioxidant effects. The pH at which the
inhibition of HNE modification of substrate was observed was close to the
physiological pH, making this formulation of curcumin potentially useful
practically.

PMID: 17116380 [PubMed - in process]

18: Biomed Mater Eng. 2006;16(5):329-36.

Antimicrobial emulsion (coating) based on biopolymer containing neem (Melia
azardichta) and turmeric (Curcuma longa) extract for wound covering.

Jagannath JH, Radhika M.

Defence Bioengineering and Electrochemical Laboratory, Bangalore, India.
[email protected]

Polymeric bio-adhesives emulsion which is biodegradable and non-toxic containing
antimicrobial agents can play an important role in preventing infection in wound
covering and coating for surgical implants. Therefore a bioadhesive polymer was
synthesized by semi-Interpenetrating Network process using blend of shellac,
casein and polyvinyl alcohol and Maleic anhydride (MA) as reactive
compatibilizer. The synthesized polymer was mixed with neem and turmeric extract
and homogenized using an emulsifier. Differential scanning calorimeter (DSC) was
used to measure the molecular miscibility of biopolymer components and emulsion
constituents. Stability of emulsion (coating) was measured by keeping property
and accelerated stability test. Antimicrobial properties were evaluated for
human pathogenic organisms namely E. coli, Staphylococcus aureus, Bacillus
cereus, and Salmonella typhimurium using well diffusion assay. The results
indicate that stability, miscibility and antimicrobial properties of bioadhesive
was satisfactory, however further in vivo studies are required to ascertain
suitability of emulsion (coating) for biomedical use.

PMID: 17075168 [PubMed - indexed for MEDLINE]

19: Nutr Cancer. 2006;55(2):126-31.

Curcumin content of turmeric and curry powders.

Tayyem RF, Heath DD, Al-Delaimy WK, Rock CL.

Clinical Nutrition and Dietetics Department, Allied Health Sciences Faculty, The
Hashemite University, Jordan.

Curcumin, derived from the rhizome curcuma longa, is one of the primary
ingredients in turmeric and curry powders that are used as spices in Middle
Eastern and Asian countries, especially on the Indian subcontinent. More
recently, laboratory studies have demonstrated that dietary curcumin exhibits
various biological activities and significantly inhibits colon tumorigenesis and
tumor size in animals. Curcumin displays both anti-inflammatory and antioxidant
properties, giving it the potential to be considered in the development of
cancer preventive strategies and applications in clinical research. Experimental
studies have shown the biological activities of the compound, but much more
information on pharmacokinetics, bioavailability, and food content are needed.
Whether the amount of curcumin in turmeric and curry powders is sufficient to
suggest effects on biological activities and cancer risk is unknown. To
determine and compare the quantitative amounts of curcumin that are present in
several brands of turmeric and curry powders, a high performance liquid
chromatography technique was used to analyze 28 spice products described as
turmeric or curry powders and two negative controls. Pure turmeric powder had
the highest curcumin concentration, averaging 3.14% by weight. The curry powder
samples, with one exception, had relatively small amounts of curcumin present,
and the variability in content was great. The curcumin content of these
seasoning products that are consumed as a component of the diet should be
considered in evaluating baseline tissue concentration and response to curcumin
supplementation, which is under study in chemoprevention trials.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17044766 [PubMed - indexed for MEDLINE]

20: J Clin Rheumatol. 2004 Oct;10(5):236-245.

A 32-Week Randomized, Placebo-Controlled Clinical Evaluation of RA-11, an
Ayurvedic Drug, on Osteoarthritis of the Knees.

Chopra A, Lavin P, Patwardhan B, Chitre D.

From the *Center for Rheumatic Diseases, Inlaks and Budhrani Hospital, Bharati
Hospital Medical College (Deemed University), Pune, India; daggerAverion, Inc.,
Framingham, Massachusetts; the double daggerSchool of Health Sciences,
University of Pune, India; and section signBIO-VED Pharmaceuticals, Inc., San
Jose, California.

BACKGROUND:: The ancient Indian (Asian) Ayurvedic medicinal system uses
herbomineral drugs to treat arthritis. Despite centuries of use, very few have
been tested by drug trials. RA-11 (ARTREX, MENDAR), a standardized multiplant
Ayurvedic drug (Withania somnifera, Boswellia serrata, Zingiber officinale, and
Curcuma longa) is currently used to treat arthritis. OBJECTIVE:: The objective
of this study was to evaluate the efficacy and safety of RA-11 in patients with
symptomatic osteoarthritis (OA) of the knees. METHODS:: A total of 358 patients
with chronic knee pain were screened free-of-cost in "arthritis camps" in an
Indian metropolis. Ninety patients with primary OA of the knees (ACR
classification; Arthritis Rheum 1986;29:1039-1049) were found eligible
(postanalgesic washout pain visual analog score [VAS] >/=40 mm in either or both
knees on body weight-bearing activities) to enroll into a randomized,
double-blind, placebo-controlled, parallel efficacy, single-center, 32-week drug
trial (80% power to detect 25% difference, P = 0.05, 2-sided). Concurrent
analgesics/nonsteroidal antiinflammatory drugs and steroids in any form were not
allowed. Lifestyle and/or dietary restrictions, as per routine Ayurveda
practices, were not imposed. Pain VAS (maximum pain in each knee recorded by the
patient during the preceding 48 hours) and modified WOMAC (Western Ontario
McMaster University OA Index, Likert scale, version 3.0) were the primary
efficacy variables. The WOMAC section on "physical function difficulty" was
modified for Indian use and validated before the trial. Routine laboratory
testing was primarily done to monitor drug safety. At baseline, the groups
(active = 45, placebo = 45) were well matched for several measures (mean pain
VAS: active = 6.17; placebo = 6.5). RESULTS:: 1) Efficacy: Compared with
placebo, the mean reduction in pain VAS at week 16 (active = 2.7, placebo = 1.3)
and week 32 (active = 2.8, placebo = 1.8) in the active group was significantly
(P <0.05, analysis of variance [ANOVA]) better. Similarly, the improvement in
the WOMAC scores at week 16 and week 32 were also significantly superior (P
<0.01, ANOVA) in the active group. 2) Safety: Both the groups reported mild
adverse events (AE) without any significant difference. 3) Withdrawals:
Twenty-eight patients were discontinued. None reported drug-related toxicity.
The majority failed follow up/compliance. No differences were observed between
the groups. CONCLUSION:: This controlled drug trial demonstrates the potential
efficacy and safety of RA- 11 in the symptomatic treatment of OA knees over 32
weeks of therapy.

PMID: 17043520 [PubMed - as supplied by publisher]

21: Brain Res. 2006 Nov 29;1122(1):56-64. Epub 2006 Oct 3.

Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF
expression and phosphorylation of CREB.

Xu Y, Ku B, Tie L, Yao H, Jiang W, Ma X, Li X.

Department of Pharmacology, School of Basic Medical Science, Peking University,
38 Xueyuan Road, Beijing, 100083, PR China.

Curcuma longa is a major constituent of the traditional Chinese medicine
Xiaoyao-san, which has been used to effectively manage stress and
depression-related disorders in China. Curcumin is the active component of
curcuma longa, and its antidepressant effects were described in our prior
studies in mouse models of behavioral despair. We hypothesized that curcumin may
also alleviate stress-induced depressive-like behaviors and
hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Thus in present study we
assessed whether curcumin treatment (2.5, 5 and 10 mg/kg, p.o.) affects behavior
in a chronic unpredictable stress model of depression in rats and examined what
its molecular targets may be. We found that subjecting animals to the chronic
stress protocol for 20days resulted in performance deficits in the shuttle-box
task and several physiological effects, such as an abnormal adrenal gland weight
to body weight (AG/B) ratio and increased thickness of the adrenal cortex as
well as elevated serum corticosterone levels and reduced glucocorticoid receptor
(GR) mRNA expression. These changes were reversed by chronic curcumin
administration (5 or 10 mg/kg, p.o.). In addition, we also found that the
chronic stress procedure induced a down-regulation of brain-derived neurotrophic
factor (BDNF) protein levels and reduced the ratio of phosphorylated cAMP
response element-binding protein (pCREB) to CREB levels (pCREB/CREB) in the
hippocampus and frontal cortex of stressed rats. Furthermore, these
stress-induced decreases in BDNF and pCREB/CREB were also blocked by chronic
curcumin administration (5 or 10 mg/kg, p.o.). These results provide compelling
evidence that the behavioral effects of curcumin in chronically stressed
animals, and by extension humans, may be related to their modulating effects on
the HPA axis and neurotrophin factor expressions.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17022948 [PubMed - indexed for MEDLINE]

22: Mol Pharmacol. 2007 Jan;71(1):61-72. Epub 2006 Oct 4.

c-Abl kinase regulates curcumin-induced cell death through activation of c-Jun
N-terminal kinase.

Kamath R, Jiang Z, Sun G, Yalowich JC, Baskaran R.

Department of Molecular Genetics and Biochemistry, University of Pittsburgh
School of Medicine, E1205 Biomedical Science Tower, Pittsburgh, PA 15261, USA.

Curcumin, a natural phenolic compound found in turmeric (Curcuma longa) exhibits
anticancer properties, attributed to its antiproliferative and
apoptosis-inducing activity. The ubiquitously expressed nonreceptor tyrosine
kinase c-Abl regulates stress responses induced by oxidative agents such as
ionizing radiation and H2O2. In this study, we show that c-Abl is an important
component of the cell death response activated by curcumin and that Abl mediates
this response partly through activation of c-Jun N-terminal kinase (JNK).
Therefore, inhibition of Abl by STI571 [imatinib (Gleevec)] treatment or
down-regulation of Abl expression through Abl-specific short-hairpin RNA (shRNA)
diminished cell death induction and JNK activation. Highlighting the
interdependent nature of the Abl and JNK signaling in the curcumin-induced cell
death response, a JNK inhibitor
[anthra(1,9-cd)pyrazol-6(2H)-one-1,9-pyrazoloanthrone (SP600125)] caused very
little cell death inhibition in STI571-pretreated cells and in Abl
shRNA-expressing cells. Moreover, treatment with Abl and JNK inhibitor alone or
together caused similar levels of cell death inhibition. Although p53 induction
in response to curcumin treatment is dependent on Abl, we found that Abl-->p53
signaling is not necessary for curcumin-induced cell death. Taken together, the
results demonstrate the differential roles played by Abl-->p53 and Abl-->JNK
signaling events in modulating the cell death response to curcumin.

Publication Types:
Research Support, N.I.H., Extramural

PMID: 17021249 [PubMed - indexed for MEDLINE]

23: Chin J Integr Med. 2006 Sep;12(3):207-11.

Study on effects of extracts from Salvia Miltiorrhiza and Curcuma Longa in
inhibiting phosphorylated extracellular signal regulated kinase expression in
rat's hepatic stellate cells.

Cheng Y, Ping J, Liu C, Tan YZ, Chen GF.

Department of Hepatocirrhosis, Shuguang Hospital, Shanghai University of
Traditional Chinese Medicine, Shanghai, China. [email protected]

OBJECTIVE: To study the effect of salvianolic acid B (SAB) and curcumin, the
extracts of Salvia Miltiorrhiza and Curcuma Longa, on the proliferation and
activation of hepatic stellate cell (HSC), and the extracellular signal
regulated kinase (ERK) expression in it. METHODS: Rat's HSC-T6 were cultured and
treated by SAB or curcumin. The inhibitory effect on cell proliferation was
determined by 3-(4, 5-dimthyl-2-2thiazoly)-2, 5-diphenyl-2H-tetrazolium bromide
(MTT) colorimetry, and the expression levels of alpha smooth actin (alpha-SMA),
collagen type I, and ERK were determined by Western blot. RESULTS: SAB and
curcumin inhibited the proliferation and activation of rat's HSC-T6 in
dose-dependent fashion and significantly reduced the expression level of
alpha-SMA (P < 0.01). Curcumin significantly reduced the expression of collagen
type I (P < 0.05). Both SAB and curcumin showed insignificant effect on the ERK
expression level, but they could significantly reduce the level of
phosphorylated-ERK expression, showing significant difference as compared with
that in the control group (P < 0.01 and P < 0.05 respectively). CONCLUSION: SAB
and curcumin could significantly inhibit the proliferation, activation of HSC,
and the production of type I collagen in HSC, the mechanism may be associated
with their inhibition on ERK phosphorylation.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17005083 [PubMed - indexed for MEDLINE]

24: Clin Exp Pharmacol Physiol. 2006 Oct;33(10):940-5.

Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic
nephropathy in rats.

Sharma S, Kulkarni SK, Chopra K.

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab
University, Chandigarh, India.

Chronic hyperglycaemia in diabetes leads to the overproduction of free radicals
and evidence is increasing that these contribute to the development of diabetic
nephropathy. Among the spices, turmeric (Curcuma longa) is used as a flavouring
and colouring agent in the indian diet every day and is known to possess
anti-oxidant properties. The present study was designed to examine the effect of
curcumin, a yellow pigment of turmeric, on renal function and oxidative stress
in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single
intraperitoneal injection of STZ (65 mg/kg) in rats. Four weeks after STZ
injection, rats were divided into four groups, namely control rats, diabetic
rats and diabetic rats treated with curcumin (15 and 30 mg/kg, p.o.) for 2
weeks. Renal function was assessed by creatinine, blood urea nitrogen,
creatinine and urea clearance and urine albumin excretion. Oxidative stress was
measured by renal malonaldehyde, reduced glutathione and the anti-oxidant
enzymes superoxide dismutase and catalase. Streptozotocin-injected rats showed
significant increases in blood glucose, polyuria and a decrease in bodyweight
compared with age-matched control rats. After 6 weeks, diabetic rats also
exhibited renal dysfunction, as evidenced by reduced creatinine and urea
clearance and proteinuria, along with a marked increase in oxidative stress, as
determined by lipid peroxidation and activities of key anti-oxidant enzymes.
Chronic treatment with curcumin significantly attenuated both renal dysfunction
and oxidative stress in diabetic rats. These results provide confirmatory
evidence of oxidative stress in diabetic nephropathy and point towards the
possible anti-oxidative mechanism being responsible for the nephroprotective
action of curcumin.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17002671 [PubMed - indexed for MEDLINE]

25: Neurosci Lett. 2006 Oct 16;407(1):53-8. Epub 2006 Sep 1.

Curcumin activated both receptor-mediated and mitochondria-mediated proteolytic
pathways for apoptosis in human glioblastoma T98G cells.

Karmakar S, Banik NL, Patel SJ, Ray SK.

Department of Neurosciences, Medical University of South Carolina, 96 Jonathan
Lucas Street, Suite 323K, P.O. Box 250606, Charleston, SC 29425, USA.

The therapeutic effect of curcumin (CCM), a polyphenolic compound from the
rhizome of Curcuma longa, has not yet been examined in glioblastoma. We used
human glioblastoma T98G cells to explore the efficacy of CCM for inducing
apoptosis and identifying proteolytic mechanisms involved in this process.
Trypan blue dye exclusion test showed decrease in cell viability with increasing
dose of CCM. Wright staining and ApopTag assay showed, respectively,
morphological and biochemical features of apoptosis in T98G cells exposed to 25
microM and 50 microM of CCM for 24 h. Treatment with CCM activated
receptor-mediated pathway of apoptosis as Western blotting showed activation of
caspase-8 and cleavage of Bid to tBid. Besides, CCM caused an increase in
Bax:Bcl-2 ratio, and mitochondrial release of cytochrome c, Second mitochondrial
activator of caspases/Direct IAP binding protein with low pI (Smac/Diablo), and
apoptosis-inducing-factor (AIF) indicating involvement of mitochondria-mediated
pathway as well. Down regulation of the nuclear factor kappa B (NFkappaB),
increased expression of inhibitor of nuclear factor kappa B alpha (IkappaB
alpha), and decreased expression of inhibitor-of-apoptosis proteins (IAPs) such
as c-IAP1 and c-IAP2 in T98G cells following CCM treatment suggested suppression
of survival signal. Activation of caspase-9 and caspase-3 was detected in
generation of 35 kD and 20 kD active fragments, respectively. Calpain and
caspase-3 activities cleaved 270 kD alpha-spectrin at specific sites to generate
145 kD spectrin break down product (SBDP) and 120 kD SBDP, respectively. Our
results strongly suggest that CCM induced both receptor-mediated and
mitochondria-mediated proteolytic mechanisms for induction of apoptosis in T98G
cells.

Publication Types:
Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

PMID: 16949208 [PubMed - indexed for MEDLINE]

26: J Pharm Biomed Anal. 2007 Jan 17;43(2):486-92. Epub 2006 Aug 23.

Quantitative determination of eight components in rhizome (Jianghuang) and
tuberous root (Yujin) of Curcuma longa using pressurized liquid extraction and
gas chromatography-mass spectrometry.

Qin NY, Yang FQ, Wang YT, Li SP.

Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR,
China.

Curcuma longa (Zingiberaceae) is a native plant of southern Asia and is
cultivated extensively throughout the warmer parts of the world. Jianghuang and
Yujin are rhizome and tuberous root of C. longa, respectively, which were
traditionally used as two Chinese medicines. In this paper, pressurized liquid
extraction (PLE) and gas chromatography-mass spectrometry (GC-MS) were developed
for quantitative determination/estimation of eight characteristic compounds
including beta-caryophyllene, ar-curcumene, zingiberene, beta-bisabolene,
beta-sesquiphellandrenendrene, ar-turmerone, alpha-turmerone and beta-turmerone
in Jianghuang and Yujin. A HP-5MS capillary column (30 m x 0.25 mm i.d.) coated
with 0.25 microm film 5% phenyl methyl siloxane was used for separation and
selected ion monitoring (SIM) method was used for quantitation. Hierarchical
cluster analysis based on characteristics of eight identified peaks in GC-MS
profiles showed that 10 samples were divided into two main clusters, Jianghuang
and Yujin, respectively. Four components such as ar-curcumene, ar-turmerone,
alpha-turmerone and beta-turmerone were optimized as markers for quality control
of rhizome (Jianghuang) and tuberous root (Yujin), which are two traditional
Chinese medicines, from Curcuma longa.

PMID: 16930909 [PubMed - in process]

27: J Ethnobiol Ethnomedicine. 2006 Aug 7;2:31.

Ethnoveterinary medicines used for horses in Trinidad and in British Columbia,
Canada.

Lans C, Turner N, Brauer G, Lourenco G, Georges K.

University of Victoria, Environmental Science, British Columbia, V8W 3P5,
Canada. [email protected]

ABSTRACT: This paper investigates the commonalities in ethnoveterinary medicine
used for horses between Trinidad (West Indies) and British Columbia (Canada).
These research areas are part of a common market in pharmaceuticals and are both
involved in the North American racing circuit. There has been very little
research conducted on medicinal plants used for horses although their use is
widespread. The data on ethnoveterinary medicines used for horses was obtained
through key informant interviews with horse owners, trainers, breeders, jockeys,
grooms and animal care specialists in two research areas: Trinidad and British
Columbia (BC). A participatory validation workshop was held in BC. An extensive
literature review and botanical identification of the plants was also done. In
all, 20 plants were found to be used in treating racehorses in Trinidad and 97
in BC. Of these the most-evidently effective plants 19 of the plants used in
Trinidad and 66 of those used in BC are described and evaluated in this paper.
Aloe vera, Curcuma longa and Ricinus communis are used in both research areas.
More research is needed in Trinidad to identify plants that respondents claimed
were used in the past. Far more studies have been conducted on the temperate and
Chinese medicinal plants used in BC and therefore these ethnoveterinary remedies
reflect stronger evidence of efficacy.

PMID: 16893454 [PubMed - in process]

28: Phytochemistry. 2006 Sep;67(18):2017-29. Epub 2006 Aug 7.

Biosynthesis of curcuminoids and gingerols in turmeric (Curcuma longa) and
ginger (Zingiber officinale): identification of curcuminoid synthase and
hydroxycinnamoyl-CoA thioesterases.

Ramirez-Ahumada Mdel C, Timmermann BN, Gang DR.

Arizona Center for Phytomedicine Research and Department of Pharmacology and
Toxicology, University of Arizona, Tucson, AZ 85721-0036, USA.

Members of the Zingiberaceae such as turmeric (Curcuma longa L.) and ginger
(Zingiber officinale Rosc.) accumulate at high levels in their rhizomes
important pharmacologically active metabolites that appear to be derived from
the phenylpropanoid pathway. In ginger, these compounds are the gingerols; in
turmeric these are the curcuminoids. Despite their importance, little is known
about the biosynthesis of these compounds. This investigation describes the
identification of enzymes in the biosynthetic pathway leading to the production
of these bioactive natural products. Assays for enzymes in the phenylpropanoid
pathway identified the corresponding enzyme activities in protein crude extracts
from leaf, shoot and rhizome tissues from ginger and turmeric. These enzymes
included phenylalanine ammonia lyase, polyketide synthases, p-coumaroyl
shikimate transferase, p-coumaroyl quinate transferase, caffeic acid
O-methyltransferase, and caffeoyl-CoA O-methyltransferase, which were evaluated
because of their potential roles in controlling production of certain classes of
gingerols and curcuminoids. All crude extracts possessed activity for all of
these enzymes, with the exception of polyketide synthases. The results of
polyketide synthase assays showed detectable curcuminoid synthase activity in
the extracts from turmeric with the highest activity found in extracts from
leaves. However, no gingerol synthase activity could be identified. This result
was explained by the identification of thioesterase activities that cleaved
phenylpropanoid pathway CoA esters, and which were found to be present at high
levels in all tissues, especially in ginger tissues. These activities may shunt
phenylpropanoid pathway intermediates away from the production of curcuminoids
and gingerols, thereby potentially playing a regulatory role in the biosynthesis
of these compounds.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 16890967 [PubMed - indexed for MEDLINE]

29: Int J Mol Med. 2006 Aug;18(2):227-31.

Curcumin inhibits telomerase activity in human cancer cell lines.

Cui SX, Qu XJ, Xie YY, Zhou L, Nakata M, Makuuchi M, Tang W.

Department of Pharmacology, Institute of Materia Medica, Shandong Academy of
Medical Sciences, Jinan, Shandong, P.R. China.

Curcumin, one of the major components of tumeric, the dried rhizome of Curcuma
longa L, has been shown to have anti-proliferating and anti-carcinogenic
properties. In this study, we examined the effects of curcumin on cell growth
and telomerase activity in human cancer cell lines Bel7402, HL60 and SGC7901.
Curcumin (1-32 microM) showed anti-proliferating effects on these cell lines in
a dose-dependent manner in vitro, and anti-tumor effects when curcumin (50-200
mg/kg) was orally administered to nude mice transplanted with the cancer cells.
When the cells were treated with 1 microM of curcumin for 120 h, apoptotic cells
were observed by means of the adridine orange/ethidium bromide staining method,
single cell microgel electrophoresis and flow cytometric analysis. On the other
hand, suppression of telomerase activity in extracts of the cells treated with 1
microM of curcumin was observed by means of a telomeric repeat amplification
protocol - silver staining assay. These results suggest that curcumin could
suppress telomerase activity in the cancer cell lines and that the decrease of
telomerase expression followed by induction of apoptosis might be involved in
the anti-proliferating effect of curcumin.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16820928 [PubMed - in process]

30: Biol Pharm Bull. 2006 Jul;29(7):1476-9.

Turmeric and curcumin modulate the conjugation of 1-naphthol in Caco-2 cells.

Naganuma M, Saruwatari A, Okamura S, Tamura H.

Kyoritsu University of Pharmacy, Tokyo, Japan.

Turmeric, the powdered dry rhizome of the Curcuma longa plant, and curcumin, the
major anti-oxidant constituent of turmeric, have been shown to possess
chemopreventive activity. To elucidate the possible interaction of turmeric and
curcumin with conjugation reactions, which in many cases are involved in the
activation of procarcinogens, we measured their effects in the conjugation of
1-naphthol in Caco-2 cells, a human colon carcinoma cell line, within a 24 h
period. Turmeric exhibits inhibitory activity toward both sulfo- and
glucuronosyl conjugations of 1-naphthol at approximately the same levels
(IC(50)=0.24 and 0.29 mg/ml, respectively). Curcumin inhibits sulfo-conjugation
at lower concentrations (IC(50)=9.7 microg/ml), but only showed weak inhibition
toward glucuronosyl conjugation of 1-naphthol in Caco-2 cells. In addition,
turmeric was found to strongly inhibit in vitro phenol sulfotransferase (SULT)
activity and demonstrate moderate inhibitory properties against UDP-glucuronosyl
transferase (UGT) activity in Caco-2 cells (IC(50)=0.17 mg/ml and 0.62 mg/ml,
respectively). Curcumin also strongly inhibits in vitro phenol sulfotransferase
activity with an IC(50) of 2.4 microg/ml. Moreover, and in contrast to the
moderate inhibition of UGT activity by turmeric and curcumin, both induce the
expression of the UGT1A1 and UGT1A6 genes, revealed by real-time PCR analysis.
These findings are indicative of a possible interaction of both turmeric and
curcumin with conjugation reactions in the human intestinal tract and colon.
This in turn may affect the bioavailability of therapeutic drugs and toxicity
levels of environmental chemicals, particularly procarcinogens.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16819192 [PubMed - indexed for MEDLINE]

31: Altern Med Rev. 2006 Jun;11(2):128-50.

Modulation of cytokine expression by traditional medicines: a review of herbal
immunomodulators.

Spelman K, Burns J, Nichols D, Winters N, Ottersberg S, Tenborg M.

Clinical Division, Department of Herbal Medicine, Tai Sophia Institute, 7750
Montpelier Road, Laurel, MD 20723, USA. [email protected]

Modulation of cytokine secretion may offer novel approaches in the treatment of
a variety of diseases. One strategy in the modulation of cytokine expression may
be through the use of herbal medicines. A class of herbal medicines, known as
immunomodulators, alters the activity of immune function through the dynamic
regulation of informational molecules such as cytokines. This may offer an
explanation of the effects of herbs on the immune system and other tissues. For
this informal review, the authors surveyed the primary literature on medicinal
plants and their effects on cytokine expression, taking special care to analyze
research that utilized the multi-component extracts equivalent to or similar to
what are used in traditional medicine, clinical phytotherapy, or in the
marketplace. METHODOLOGY: MEDLINE, EBSCO, and BIOSIS were used to identify
research on botanical medicines, in whole or standardized form, that act on
cytokine activity through different models, i.e., in vivo (human and animal), ex
vivo, or in vitro. RESULTS: Many medicinal plant extracts had effects on at
least one cytokine. The most frequently studied cytokines were IL-1, IL-6, TNF,
and IFN. Acalypha wilkesiana, Acanthopanax gracilistylus, Allium sativum, Ananus
comosus, Cissampelos sympodialis, Coriolus versicolor, Curcuma longa, Echinacea
purpurea, Grifola frondosa, Harpagophytum procumbens, Panax ginseng, Polygala
tenuifolia, Poria cocos, Silybum marianum, Smilax glabra, Tinospora cordifolia,
Uncaria tomentosa, and Withania somnifera demonstrate modulation of multiple
cytokines. CONCLUSION: The in vitro and in vivo research demonstrates that the
reviewed botanical medicines modulate the secretion of multiple cytokines. The
reported therapeutic success of these plants by traditional cultures and modern
clinicians may be partially due to their effects on cytokines. Phytotherapy
offers a potential therapeutic modality for the treatment of many differing
conditions involving cytokines. Given the activity demonstrated by many of the
reviewed herbal medicines and the increasing awareness of the broad-spectrum
effects of cytokines on autoimmune conditions and chronic degenerative
processes, further study of phytotherapy for cytokine-related diseases and
syndromes is warranted.

Publication Types:
Review

PMID: 16813462 [PubMed - indexed for MEDLINE]

32: Ann N Y Acad Sci. 2006 May;1067:394-9.

Curcumin's biphasic hormetic response on proteasome activity and heat-shock
protein synthesis in human keratinocytes.

Ali RE, Rattan SI.

Laboratory of Cellular Ageing, Danish Centre for Molecular Gerontology,
Department of Molecular Biology, University of Aarhus, Denmark.

Curcumin (diferuloylmethane), is a component of the yellow powder prepared from
the roots of Curcuma longa (Zingiberaceae), also known as tumeric or turmeric.
It is widely cultivated and used as a food ingredient in tropical areas of Asia
and Central America. Treatment of mid-passage human epidermal keratinocytes with
curcumin resulted in a biphasic hormetic dose-response with respect to
proteasome activity. Curcumin treatment (up to 1 microM for 24 h) increased
chymotrypsin-like activity by 46% compared to that in untreated keratinocytes.
However, higher concentrations of curcumin were inhibitory, and at 10 microM the
proteasome activity decreased to 46% of its initial value. Furthermore, the
preincubation of human keratinocytes at 43 degrees C for 1 h, followed by 24-h
treatment with 3 microM curcumin, led to an increase in heat-shock protein
(hsp70 and hsp90) levels by 24% and 19%, respectively, and the effect was
sustained at concentrations up to 10 microM. On the other hand, the level of the
small hsp27 was unaffected by curcumin concentrations of 0.3-1 microM, while it
decreased by 34% at 10 microM.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 16804017 [PubMed - indexed for MEDLINE]

33: Evid Based Complement Alternat Med. 2006 Jun;3(2):255-60. Epub 2006 Apr 5.

Comparison of Anti-inflammatory Activities of Six Curcuma Rhizomes: A Possible
Curcuminoid-independent Pathway Mediated by Curcuma phaeocaulis Extract.

Tohda C, Nakayama N, Hatanaka F, Komatsu K.

We aimed to compare the anti-inflammatory activities of six species of Curcuma
drugs using adjuvant arthritis model mice. When orally administered 1 day before
the injection of adjuvant, the methanol extract of Curcuma phaeocaulis
significantly inhibited paw swelling and the serum haptoglobin concentration in
adjuvant arthritis mice. Also when orally administered 1 day after the injection
of adjuvant, the methanol extract of Curcuma phaeocaulis significantly inhibited
paw swelling. Other Curcuma species (Curcuma longa, Curcuma wenyujin, Curcuma
kwangsiensis, Curcuma zedoaria and Curcuma aromatica) had no significant
inhibitory effects on adjuvant-induced paw swelling. Cyclooxygenase (COX)-2
activity was significantly inhibited by the methanol extract of C. phaeocaulis.
Curcuminoids' (curcumin, bis-demethoxycurcumin and demethoxycurcumin) were rich
in C. longa, but less in C. phaeocaulis and C. aromatica, not in C. wenyujin, C.
kwangsiensis and C. zedoaria, suggesting that curcuminoids' contents do not
relate to inhibition of arthritis swelling. Therefore, C. phaeocaulis may be a
useful drug among Curcuma species for acute inflammation, and the active
constituents of C. phaeocaulis are not curcuminoids.

PMID: 16786056 [PubMed - in process]

34: J Soc Integr Oncol. 2006 Winter;4(1):21-6.

Down-regulation of prostaglandin E2 by curcumin is correlated with inhibition of
cell growth and induction of apoptosis in human colon carcinoma cell lines.

Lev-Ari S, Maimon Y, Strier L, Kazanov D, Arber N.

Unit of Complementary Medicine and Department of Cancer Prevention, Tel Aviv
Medical Center, Tel Aviv, Israel.

Several in vitro and in vivo studies have demonstrated an association between
curcumin, a diferuloylmethane derived from the plant Curcuma longa, and
colorectal cancer (CRC) prevention. Nevertheless, the molecular mechanism
responsible for the chemopreventive effect of curcumin is not well understood
and most probably involves several pathways. Several studies indicate that
curcumin may exert its effect by specifically inhibiting the cyclooxygenase-2
(COX-2) isoenzyme, which is up-regulated in 40 to 50% of colorectal polyps and
in up to 85% of CRCs. However, other studies have suggested that curcumin may
also inhibit polyps formation by COX-2 independent mechanisms (eg, inhibition of
ErbB-1, AkT). The aim of this study was to evaluate whether curcumin's effect on
the inhibition of cell growth and induction of apoptosis in human colon
carcinoma cell lines is correlated with inhibition of PGE2 synthesis and
down-regulation of COX-2. HT29 cells (expressing COX-2) and SW480 (deficient of
COX-2) were exposed to different concentrations (0-50 microM) of curcumin for 72
hours. Growth inhibition was assessed by Coulter counter. Cell viability was
assessed by the ability of metabolically active cells to reduce tetrazolium salt
to colored formazan compounds (tetrazolium salt assay). Apoptosis was measured
by two independent methods: flow cyto-metric analysis and
4'-6-Diamidino-2-phenylindole (DAPI) staining. Activity of COX-2 was evaluated
by measuring prostaglandin E2 (PGE2) concentration using a specific
enzyme-linked immunoassay. COX-1 and COX-2 expressions were measured by Western
blot analysis. There was a significant difference between curcumin effect on
COX-2-expressing (HT29: inhibitory concentration 50% [IC50] = 15 microM) and
COX-2-deficient (SW480: IC50 = 40 microM) cells. Similarly, induction of
apoptosis was higher in cells expressing COX-2. Western blot analysis and PGE2
immunoassay showed that curcumin inhibited COX-2 protein activity and expression
in a dose-dependent manner. In conclusion, inhibition of cell survival and
induction of apoptosis by curcumin in colorectal adenocarcinoma cell lines is
associated with the inhibition of PGE2 synthesis and down-regulation of COX-2.

Publication Types:
Comparative Study

PMID: 16737669 [PubMed - indexed for MEDLINE]

35: Int J Cancer. 2006 Oct 15;119(8):1811-8.

Resistance to apoptosis of HCW-2 cells can be overcome by curcumin- or
vincristine-induced mitotic catastrophe.

Magalska A, Sliwinska M, Szczepanowska J, Salvioli S, Franceschi C, Sikora E.

Department of Cellular Biochemistry, Nencki Institute of Experimental Biology,
Warsaw, Poland.

The term mitotic catastrophe has recently become widely used to describe a form
of death affecting many cancer cells, which, because of severe DNA or mitotic
spindle damage, are not able to bypass mitosis. We show here that cells of the
HL-60-derived HCW-2 line highly resistant to apoptosis, upon treatment with
curcumin or vincristine, undergo mitotic catastrophe that is finalized by
caspase 3 activation and oligonucleosomal DNA degradation. Curcumin is a natural
dye, derived from Curcuma longa that has been shown to induce cell death in many
cancer cells. Both treatments decrease cell proliferation and cell survival,
arrest cells in G2/M phase of cell cycle and induce morphological changes
characterized by cell enlargement and micronucleation. "Catastrophic" cells
comprise a separate subpopulation with less than 4C DNA, as evidenced by flow
and scanning cytometry. This subpopulation is MPM-2 positive. Thymidine block
increased the number of cell arrested in the G2/M phase of cell cycle and
curcumin effectiveness as an inducer of mitotic catastrophe. Curcumin, but not
vincristine, acts on HCW-2 cells by inhibiting the expression of survivin, a
modulator of cell division and apoptosis in cancer. Altogether our results show
that apoptosis resistance can be overcome by inducing mitotic catastrophe in
HCW-2 cells. Copyright 2006 Wiley-Liss, Inc.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16721786 [PubMed - indexed for MEDLINE]

36: Anticancer Agents Med Chem. 2006 May;6(3):259-70.

Biological effects of curcumin and its role in cancer chemoprevention and
therapy.

Singh S, Khar A.

Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India.

Curcumin, a natural component of the rhizome of curcuma longa has emerged as one
of the most powerful chemopreventive and anticancer agents. Its biological
effects range from antioxidant, anti-inflammatory to inhibition of angiogenesis
and is also shown to possess specific antitumoral activity. The molecular
mechanism of its varied cellular effects has been studied in some details and it
has been shown to have multiple targets and interacting macromolecules within
the cell. Curcumin has been shown to possess anti-angiogenic properties and the
angioinhibitory effects of curcumin manifest due to down regulation of
proangiogenic genes such as VEGF and angiopoitin and a decrease in migration and
invasion of endothelial cells. One of the important factors implicated in
chemoresistance and induced chemosensitivity is NFkB and curcumin has been shown
to down regulate NFkB and inhibit IKB kinase thereby suppressing proliferation
and inducing apoptosis. Cell lines that are resistant to certain apoptotic
inducers and radiation become susceptible to apoptosis when treated in
conjunction with curcumin. Besides this it can also act as a chemopreventive
agent in cancers of colon, stomach and skin by suppressing colonic aberrant
crypt foci formation and DNA adduct formation. This review focuses on the
various aspects of curcumin as a potential drug for cancer treatment and its
implications in a variety of biological and cellular processes vis-a-vis its
mechanism of action.

Publication Types:
Review

PMID: 16712454 [PubMed - indexed for MEDLINE]

37: Mol Cell Biochem. 2006 Aug;288(1-2):115-23. Epub 2006 May 12.

Curcumin combats against cigarette smoke and ethanol-induced lipid alterations
in rat lung and liver.

Vanisree AJ, Sudha N.

Department of Biochemistry, University of Madras, Guindy Campus, Chennai,
600033, Tamilnadu, India. [email protected]

BACKGROUND: Human population, in spite of the medical and scientific
achievements, still fall as a prey to the evils of habitual smoking and alcohol,
thus necessitating safer counteracting measures. Objective: To evaluate the
effect of cotreatment of curcumin (Curcuma longa) in rats subjected to acute
exposure to cigarette smoke (CS) and ethanol (EtOH). METHODOLOGY: Of the four
groups of experimental rats, a set of rats was subjected to whole body exposure
to cigarette smoke along with ethanol administration serving as a model of
CS+EtOH injury. Curcumin treatment was given to two sets of rats: (i) one set
receiving simultaneous CS+EtOH and (ii) one set of normal rats without any
administration. The other group of rats served as control. Blood, liver and lung
of rats were selected for assessment of CS+EtOH injury as well as curcumin
treatment. RESULT: Altered lipid, lipoprotein profile and bile acid excretion
were observed in CS+EtOH rats along with premalignant pathological state in
tissues. In treated rats, the levels were maintained at near-normal levels along
with near-normal histology. CONCLUSION: This biochemical picture on cotreatment
with curcumin suggests that curcumin could counteract the injurious effects of
combined CS and EtOH and thus might help to reduce the risk of hyperlipidemic
disorders which develop due to smoking and drinking.

PMID: 16691314 [PubMed - indexed for MEDLINE]

38: Biochem Pharmacol. 2006 Jun 28;72(1):62-9. Epub 2006 Apr 1.

Inhibition of homodimerization of Toll-like receptor 4 by curcumin.

Youn HS, Saitoh SI, Miyake K, Hwang DH.

USDA, ARS, Western Human Nutrition Research Center, and Department of Nutrition,
University of California, Davis, Meyer Hall, One Shields Ave., CA 95616, USA.

Toll-like receptors play a key role in sensing microbial components and inducing
innate immune responses. Ligand-induced dimerization of TLR4 is required for the
activation of downstream signaling pathways. Thus, the receptor dimerization may
be one of the first lines of regulation in activating TLR-mediated signaling
pathways and induction of subsequent immune responses. LPS induces the
activation of NF-kappaB and IRF3 through MyD88- or TRIF-dependent pathways.
Curcumin, a polyphenol found in the plant Curcuma longa, has been shown to
suppress the activation of NF-kappaB induced by various pro-inflammatory stimuli
by inhibiting IKKbeta kinase activity in MyD88-dependent pathway. Curcumin also
inhibited LPS-induced IRF3 activation. These results imply that curcumin
inhibits both MyD88- and TRIF-dependent pathways in LPS-induced TLR4 signaling.
However, in TRIF-dependent pathway, curcumin did not inhibit IRF3 activation
induced by overexpression of TRIF in 293T cells. These results suggest that TLR4
receptor complex is the molecular target of curcumin in addition to IKKbeta.
Here, we report biochemical evidence that phytochemicals (curcumin and
sesquiterpene lactone) inhibit both ligand-induced and ligand-independent
dimerization of TLR4. Furthermore, these results demonstrate that small
molecules with non-microbial origin can directly inhibit TLRs-mediated signaling
pathways at the receptor level. These results imply that the activation of TLRs
and subsequent immune/inflammatory responses induced by endogenous molecules or
chronic infection can be modulated by certain dietary phytochemicals we consume
daily.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 16678799 [PubMed - indexed for MEDLINE]

39: Biol Pharm Bull. 2006 May;29(5):938-44.

Ethanolic extracts from Curcuma longa attenuates behavioral, immune, and
neuroendocrine alterations in a rat chronic mild stress model.

Xia X, Pan Y, Zhang WY, Cheng G, Kong LD.

State Key Laboratory of Pharmaceutical Biotechnology, Immunobiological
Laboratory, Nanjing University, PR China.

The ethanolic extracts from the rhizome of Curcuma longa L. (turmeric),
possesses a wide variety of biological activities related to the treatment and
prevention of affective disorders. To study their antidepressant effects, the
impacts of chronic mild stress (CMS) and of the subsequent administration of
ethanolic extracts of C. longa were investigated. Male Sprague-Dawley rats
subjected to the CMS procedure demonstrated increased serum interleukin-6 and
tumor necrosis factor-alpha levels, as well as a reduction of natural killer
cell activity in splenocytes. In addition, CMS-treated rats exhibited elevated
corticotropin-releasing factor in serum and medulla oblongata and cortisol
levels in serum, with no significant change in serum adrenocorticotropin hormone
levels. The preferential behavior of reduction in sucrose intake was also
observed. These findings indicate that the alterations in immune and
hypothalamic-pituitary-adrenal (HPA) axis systems could participate in the
behavioral response to the CMS procedure in animals. Administration of ethanolic
extracts of C. longa largely reversed the above effects. These results
demonstrate the antidepressant-like activity of ethanolic extracts of C. longa
in the rat CMS model of depression, at least in part by improving the
abnormalities in immune and the HPA axis functions.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16651723 [PubMed - indexed for MEDLINE]

40: Food Chem Toxicol. 2006 Aug;44(8):1362-71. Epub 2006 Mar 9.

Dosage effects of curcumin on cell death types in a human osteoblast cell line.

Chan WH, Wu HY, Chang WH.

Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan
Christian University, Chung Li, Taiwan.

Curcumin, the yellow pigment of Curcuma longa, is known to have antioxidant and
anti-inflammatory properties, as well as their ability to either induce or
prevent cell apoptosis. However, the precise molecular mechanisms of these
effects are unknown. Here, we demonstrate that curcumin can induce apoptotic
changes, including JNK activation, caspase-3 activation, and cleavage of PARP
and PAK2, at treatment concentrations lower than 25 microM in human osteoblast
cells. In contrast, treatment with 50-200 microM of curcumin does not induce
apoptosis, but rather triggers necrotic cell death in human osteoblasts. Using
the cell permeable dye 2',7'-dichlorofluorescin diacetate (DCF-DA) as an
indicator of reactive oxygen species (ROS) generation, we found that while
treatment with 12.5-25 microM curcumin directly increased intracellular
oxidative stress, 50-200 microM curcumin had far less effect. Pretreatment of
cells with N-acetyl cysteine or alpha-tocopherol, two well known ROS scavengers,
attenuated the intracellular ROS levels increases and converted the apoptosis to
necrosis induced by 12.5-25 microM curcumin. Moreover, we observed a
dose-dependent decrease in intracellular ATP levels after treatment of
osteoblast cells with curcumin and pretreatment of cells with antimycin or
2-deoxyglucose to cause ATP depletion significantly converted 12.5-25 microM
curcumin-induced apoptosis to necrosis, indicating that ATP (a known mediator of
apoptotic versus necrotic death) is most likely involved in the switching
mechanism. Overall, our results signify that curcumin dosage treatment
determines the possible effect on ROS generation, intracellular ATP levels, and
cell apoptosis or necrosis in osteoblast cells.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16624471 [PubMed - indexed for MEDLINE]

41: Oncol Rep. 2006 May;15(5):1225-31.

Induction of G2/M arrest and inhibition of cyclooxygenase-2 activity by curcumin
in human bladder cancer T24 cells.

Park C, Kim GY, Kim GD, Choi BT, Park YM, Choi YH.

Department of Biochemistry, Dongeui University College of Oriental Medicine,
Busan 614-052, Korea. [email protected]

Curcumin, a polyphenol compound derived from Curcuma longa Linn, has been
recognized as a promising anti-cancer drug due to its multiple properties
including anti-inflammatory, anti-oxidant and anti-carcinogenic activities. To
elucidate the mechanisms by which curcumin inhibits human bladder carcinoma T24
cell proliferation, we tested the effects of curcumin on specific cell cycle
pathways and on the expression of cyclooxygenases (COXs). Curcumin inhibited the
growth of T24 cells and induced G2/M arrest in a concentration-dependent manner,
effects associated with the down-regulation of cyclin A and up-regulation of
cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1). However, other G2/M
regulatory molecules, such as cyclin A, Cdc2, Cdk2, Wee1 and Cdc25C, were not
modulated by curcumin treatment. Furthermore, curcumin decreased the levels of
COX-2 mRNA and protein expression without significant changes in the levels of
COX-1, which correlated with a decrease in prostaglandin E2 (PGE2) synthesis.
These observations suggest that curcumin may have therapeutic potential for
bladder cancer patients.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16596191 [PubMed - indexed for MEDLINE]

42: Int J Cancer. 2006 Aug 15;119(4):757-64.

Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways
in cancer cells.

Beevers CS, Li F, Liu L, Huang S.

Department of Biochemistry and Molecular Biology and Feist-Weiller Cancer
Center, Louisiana State University Health Sciences Center, Shreveport, LA
71130-3932, USA.

Curcumin (diferuloylmethane), a polyphenol natural product of the plant Curcuma
longa, is undergoing early clinical trials as a novel anticancer agent. However,
the anticancer mechanism of curcumin remains to be elucidated. Here we show that
curcumin inhibited growth of rhabdomyosarcoma cells (Rh1 and Rh30) (IC50 = 2-5
microM) and arrested cells in G1 phase of the cell cycle. Curcumin also induced
apoptosis and inhibited the basal or type I insulin-like growth factor-induced
motility of the cells. At physiological concentrations (2.5 microM), curcumin
rapidly inhibited phosphorylation of the mammalian target of rapamycin (mTOR)
and its downstream effector molecules, p70 S6 kinase 1 (S6K1) and eukaryotic
initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), in a panel of cell
lines (Rh1, Rh30, DU145, MCF-7 and Hela). Curcumin also inhibited
phosphorylation of Akt in the cells, but only at high concentrations (>40
microM). The data suggest that curcumin may execute its anticancer activity
primarily by blocking mTOR-mediated signaling pathways in the tumor cells.
Copyright 2006 Wiley-Liss, Inc.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16550606 [PubMed - indexed for MEDLINE]

43: Arch Pharm (Weinheim). 2006 Mar;339(3):123-8.

Curcumin analogs as potent aldose reductase inhibitors.

Du ZY, Bao YD, Liu Z, Qiao W, Ma L, Huang ZS, Gu LQ, Chan AS.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.

In the present study, curcuminoids isolated from curcuma longa were demonstrated
to possess inhibitory activities on bovine lens aldose reductase. In order to
find more potent aldose reductase inhibitor, curcumin analogs were synthesized
and evaluated for their ability to inhibit bovine lens aldose reductase enzyme.
The results indicated that the compounds with tetrahydroxyl groups,
2,6-bis(3,4-dihydroxybenzylidene)cyclohexanone (A(2)),
2,5-bis(3,4-dihydroxybenzylidene)cyclopentanone (B(2)),
1,5-bis(3,4-dihydroxyphenyl)-1,4-pentadiene-3-one (C(2)), and
3,5-bis(3,4-dihydroxybenzylidene)-4-piperidone (D(2)) showed remarkably potent
inhibitory effects on aldose reductase with IC(50) of 2.9 microM, 2.6 microM,
3.4 microM, and 4.9 microM, respectively. The structure-activity relationship
revealed that the curcumin analogs with ortho-dihydroxyl groups could form a
more tight affinity with aldose reductase to exert more potential inhibitory
activities.

PMID: 16528793 [PubMed - indexed for MEDLINE]

44: Mol Carcinog. 2006 May;45(5):320-32.

Antitumor action of curcumin in human papillomavirus associated cells involves
downregulation of viral oncogenes, prevention of NFkB and AP-1 translocation,
and modulation of apoptosis.

Divya CS, Pillai MR.

Department of Molecular Medicine, Regional Cancer Centre, Thiruvananthapuram,
Kerala, India.

Curcumin (diferuloyl methane), the major yellow pigment from the rhizomes of
turmeric (Curcuma longa Linn), has anticancer properties. Infection with
high-risk human papillomaviruses (HPV) leads to development of cervical
carcinoma, predominantly through the action of viral oncoproteins E6 and E7.The
present study aims at analyzing the antitumor and antiviral properties of
curcumin, on HPV associated cervical cancer cells. Our findings indicate
curcumin to be cytotoxic to cervical cancer cells in a concentration-dependent
and time-dependent manner. The cytotoxic activity was selectively more in HPV16
and HPV18 infected cells compared to non-HPV infected cells. Balance between
tumor cell proliferation and spontaneous cell death via apoptosis had an
important role in regulation of tumor cell growth. Curcumin-induced apoptosis in
cervical cancer cells. Morphological hallmarks of apoptosis such as nuclear
fragmentation and internucleosomal fragmentation of DNA were observed. Curcumin
also selectively inhibited expression of viral oncogenes E6 and E7, evident from
RT-PCR and Western blotting data. Electrophoretic mobility shift assay revealed
that activation of NFkappaB-induced by TNFalpha is down regulated by curcumin.
Curcumin blocked IkBalpha phosphorylation and degradation, leading to abrogation
of NFkappaB activation. Curcumin also down regulated the expression of COX-2, a
gene regulated by NFkappaB. Binding of AP-1, an indispensable component for
efficient epithelial tissue-specific gene expression of HPV was also selectively
down regulated by curcumin. These results provide attractive data for the
possible use of curcumin in the management of HPV associated tumors. (c) 2006
Wiley-Liss, Inc.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16526022 [PubMed - indexed for MEDLINE]

45: Przegl Lek. 2005;62(10):1180-1.

[Preventive role of curcumin in lung cancer]

[Article in Polish]

Balcerek M, Matlawska I.

Katedra i Zaklad Farmakognozji Collegium Medicum Uniwersytetu Mikolaja Kopernika
w Bydgoszczy.

Carcinogens from cigarette smoke form the link between nicotine addiction and
lung cancer, which is the leading cause of cancer-related mortality in the
world. One of the most frequently studied chemopreventive agents is a curcumin,
a natural compound extracted from turmeric that inhibits cell proliferation and
induces apoptosis in human leukaemia, prostate cancer, and non-small cell lung
cancer. Curcumin (diferuoylmethane) is a major yellow pigment in turmeric
(Curcuma longa) and is widely used as a spice. Curcumin exhibits a variety of
pharmacological effects, and has been reported to have anti-inflammatory and
anti-tumor activities.

Publication Types:
English Abstract
Review

PMID: 16521985 [PubMed - indexed for MEDLINE]

46: Indian J Med Res. 2005 Dec;122(6):525-8.

The effect of methanolic extract of Tamarindus indica Linn. on the growth of
clinical isolates of Burkholderia pseudomallei.

Muthu SE, Nandakumar S, Rao UA.

Burkholderia Laboratory, Department of Microbiology, Dr ALM Postgraduate
Institute of Basic Medical Sciences, University of Madras, Chennai, India.

Burkholderia pseudomallei (Pseudomonas pseudomallei) causes melioidosis, a
life-threatening infection common among paddy cultivators in Southeast Asian
countries. No plant materials have been investigated for its activity against B.
pseudomallei. Therefore, a preliminary study was carried out using disc
diffusion and minimum inhibitory concentration (MIC) methods to evaluate the
anti-B. pseudomallei activity of five Indian medicinal plants documented to have
been used for several ailments in the ancient Indian scriptures. The leaf
extracts of Tamarindus indica, Lawsonia inermis, and Hibiscus rosa-sinensis, the
rhizome extracts of Curcuma longa and the seeds of Vigna radiata were prepared
using methanol as solvent. The disc diffusion and MIC methods were used to
assess the anti-B. pseudomallei activity of the plants tested. Only methanol
leaf extracts of Tamarindus indica exhibited anti-B. pseudomallei activity
starting from disc concentrations of 150 mug by the disc diffusion method. The
other plants failed to show any zone of inhibition. MIC assay revealed that the
MIC and minimum bactericidal concentration (MBC) for B. pseudomallei were 125
mug/ml. Our preliminary finding showed that methanolic extracts of Tamarindus
indica has anti-B. pseudomallei inhibitory potentials under in vitro conditions.
Extensive animal studies may be required before investigating the role of
Tamarindus indica for treating melioidosis.

Publication Types:
In Vitro

PMID: 16518004 [PubMed - indexed for MEDLINE]

47: BMC Complement Altern Med. 2006 Feb 19;6:3.

Effect of Curcuma longa and Ocimum sanctum on myocardial apoptosis in
experimentally induced myocardial ischemic-reperfusion injury.

Mohanty I, Arya DS, Gupta SK.

Department of Pharmacology, All India Institute of Medical Sciences, Ansari
Nagar, New Delhi-110029, India. [email protected]

BACKGROUND: In the present investigation, the effect of Curcuma longa (Cl) and
Ocimum sanctum (Os) on myocardial apoptosis and cardiac function was studied in
an ischemia and reperfusion (I-R) model of myocardial injury. METHODS: Wistar
albino rats were divided into four groups and orally fed saline once daily
(sham, control IR) or Cl (100 mg/kg; Cl-IR) or Os (75 mg/kg; Os-IR) respectively
for 1 month. On the 31st day, in the rats of the control IR, Cl-IR and Os-IR
groups LAD occlusion was undertaken for 45 min, and reperfusion was allowed for
1 h. The hemodynamic parameters{mean arterial pressure (MAP), heart rate (HR),
left ventricular end-diastolic pressure (LVEDP), left ventricular peak positive
(+) LVdP/dt (rate of pressure development) and negative (-) LVdP/dt (rate of
pressure decline)} were monitored at pre-set points throughout the experimental
duration and subsequently, the animals were sacrificed for
immunohistopathological (Bax, Bcl-2 protein expression & TUNEL positivity) and
histopathological studies. RESULTS: Chronic treatment with Cl significantly
reduced TUNEL positivity (p < 0.05), Bax protein (p < 0.001) and upregulated
Bcl-2 (p < 0.001) expression in comparison to control IR group. In addition, Cl
demonstrated mitigating effects on several myocardial injury induced hemodynamic
{(+)LVdP/dt, (-) LVdP/dt & LVEDP} and histopathological perturbations. Chronic
Os treatment resulted in modest modulation of the hemodynamic alterations (MAP,
LVEDP) but failed to demonstrate any significant antiapoptotic effects and
prevent the histopathological alterations as compared to control IR group.
CONCLUSION: In the present study, significant cardioprotection and functional
recovery demonstrated by Cl may be attributed to its anti-apoptotic property. In
contrast to Os, Cl may attenuate cell death due to apoptosis and prevent the
impairment of cardiac performance.

PMID: 16504000 [PubMed - indexed for MEDLINE]

48: Saudi Med J. 2006 Feb;27(2):264-6.

Evidence that curcuma longa possesses an active hypolipidemic effects in
rabbits.

Khouri NA.

Department of Anatomy, Faculty of Medicine, Jordan University of Science and
Technology, Irbid. [email protected]

PMID: 16501692 [PubMed - indexed for MEDLINE]

49: J Chromatogr A. 2006 Apr 7;1111(1):21-31. Epub 2006 Feb 21.

Use of liquid chromatography-electrospray ionization tandem mass spectrometry to
identify diarylheptanoids in turmeric (Curcuma longa L.) rhizome.

Jiang H, Timmermann BN, Gang DR.

Arizona Center for Phytomedicine Research, College of Pharmacy, University of
Arizona, Tucson, 85721, USA.

LC-ESI-MS/MS coupled to DAD analysis was used as an on-line tool for
identification of diarylheptanoids in fresh turmeric rhizome extracts. Based on
their mass spectra, from both negative and positive mode LC-ESI-MS/MS analysis,
and supported by their DAD spectra, 19 diarylheptanoids were identified. Among
these 19 compounds, curcumin, demethoxycurcumin, and bisdemethoxycurcumin were
identified by comparing their chromatographic and spectral data with those of
authentic standard compounds. The other diarylheptanoid compounds were
identified or tentatively identified based on comparison to the three
curcuminoids and each other. Twelve of the identified diarylheptanoids have not
been previously reported from turmeric and six of these are new compounds.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 16490201 [PubMed - indexed for MEDLINE]

50: Integr Cancer Ther. 2006 Mar;5(1):9-29.

Targeting angiogenesis with integrative cancer therapies.

Yance DR Jr, Sagar SM.

Center for Natural Healing, Ashland, Oregon, USA.

An integrative approach for managing a patient with cancer should target the
multiple biochemical and physiological pathways that support tumor development
while minimizing normal tissue toxicity. Angiogenesis is a key process in the
promotion of cancer. Many natural health products that inhibit angiogenesis also
manifest other anticancer activities. The authors will focus on natural health
products (NHPs) that have a high degree of antiangiogenic activity but also
describe some of their many other interactions that can inhibit tumor
progression and reduce the risk of metastasis. NHPs target various molecular
pathways besides angiogenesis, including epidermal growth factor receptor
(EGFR), the HER-2/neu gene, the cyclooxygenase-2 enzyme, the NF-kB transcription
factor, the protein kinases, Bcl-2 protein, and coagulation pathways. The
herbalist has access to hundreds of years of observational data on the
anticancer activity of many herbs. Laboratory studies are confirming the
knowledge that is already documented in traditional texts. The following herbs
are traditionally used for anticancer treatment and are antiangiogenic through
multiple interdependent processes that include effects on gene expression,
signal processing, and enzyme activities: Artemisia annua (Chinese wormwood),
Viscum album (European mistletoe), Curcuma longa (turmeric), Scutellaria
baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed
extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green
tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinale (ginger), Panax
ginseng, Rabdosia rubescens (rabdosia), and Chinese destagnation herbs. Quality
assurance of appropriate extracts is essential prior to embarking on clinical
trials. More data are required on dose response, appropriate combinations, and
potential toxicities. Given the multiple effects of these agents, their future
use for cancer therapy probably lies in synergistic combinations. During active
cancer therapy, they should generally be evaluated in combination with
chemotherapy and radiation. In this role, they act as biological response
modifiers and adaptogens, potentially enhancing the efficacy of the so-called
conventional therapies. Their effectiveness may be increased when multiple
agents are used in optimal combinations. New designs for trials to demonstrate
activity in human subjects are required. Although controlled trials might be
preferred, smaller studies with appropriate end points and surrogate markers for
antiangiogenic response could help prioritize agents for the larger
resource-intensive phase 3 trials.

Publication Types:
Comparative Study
Review

PMID: 16484711 [PubMed - indexed for MEDLINE]

51: Eur J Pharmacol. 2006 Mar 18;534(1-3):55-62. Epub 2006 Feb 14.

Curcumin inhibits the proliferation and mineralization of cultured osteoblasts.

Notoya M, Nishimura H, Woo JT, Nagai K, Ishihara Y, Hagiwara H.

Department of Biological Sciences, Tokyo Institute of Technology, 4259
Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.

The effects of curcumin, which is an important constituent of rhizomes of the
plant Curcuma longa Linn, on the metabolism of osteoblasts were examined in
cultures of rat calvarial osteoblastic cells (ROB cells). The proliferation of
cells was markedly inhibited upon exposure of cells to curcumin at 5x10(-6) to
1x10(-5) M. Curcumin at 1x10(-5) M did not induce apoptosis in ROB cells but
arrested cells at the G1 phase of the cell cycle. In addition, curcumin
stimulated the expression of mRNA for p21(WAF1/CIP1), which inhibits the
activity of cyclin-dependent kinases, and inhibited the phosphorylation of
histone H1. Furthermore, curcumin reduced the rate of deposition of calcium and
the formation of mineralized nodules. Our results indicate that curcumin might
inhibit the proliferation and mineralization of osteoblastic cells through the
expression of p21(WAF1/CIP1).

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16476424 [PubMed - indexed for MEDLINE]

52: J Ethnopharmacol. 2006 Jun 30;106(2):149-57. Epub 2006 Feb 13.

Ethnobotany of medicinal plants used by Assamese people for various skin
ailments and cosmetics.

Saikia AP, Ryakala VK, Sharma P, Goswami P, Bora U.

Department of Biotechnology, Indian Institute of Technology Guwahati, North
Guwahati-781039, Assam, India.

The present paper deals with the medicinal plants used by the people of Assam
for curing different skin ailments and for cosmetics. A total of 85 plants
belonging to 49 families have been documented for their therapeutic use against
skin diseases and as herbal care. The herbal medicines were prepared from
various plant parts of single plant, or multiple plants. The majority of the
preparation was made using water as the medium. The mode of application was
topical, but in many cases it was also administered orally. In several cases the
pure herbal preparations was administered along with milk, ghee, honey, coconut
oil, curd, etc. Remedies for 18 skin ailments were documented through this
study. About 14 plants are known for their use to cure multiple skin diseases.
Among these Curcuma longa and Melia azaderach constitute the major plants. The
herbal cosmetic products used by the people of Assam ranges from the enhancement
of skin colour, hair care, removal of ugly spots, colouring of nails, palms, and
teeth. However, many of the plant preparations used for enhancing beauty were
also applied for therapeutic use. Herbal remedies were also available for skin
burns, prickly heat and pimples. Information on nine plants used for managing
dry skin also emerged from this study.

PMID: 16473486 [PubMed - indexed for MEDLINE]

53: Biol Pharm Bull. 2006 Feb;29(2):253-60.

Suppressive effects of JCICM-6, the extract of an anti-arthritic herbal formula,
on the experimental inflammatory and nociceptive models in rodents.

Zhou H, Wong YF, Cai X, Liu ZQ, Jiang ZH, Bian ZX, Xu HX, Liu L.

School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong
Kong, China.

JCICM-6, the extract of an anti-arthritic herbal formula composed of medicinal
herbs of Sinomenium acutum, Aconitum carmichaeli DEBX., Curcuma Longa L.,
Paeonia lactiflora PALL., and Paeonia suffruticosa ANDR., was examined in the
effectiveness and mechanism in reducing experimentally-induced inflammation and
nociception using nine animal models. JCICM-6 was extracted from herbs and
purified with Amberlite XAD-7HP adsorbent resin and analyzed with
HPLC-fingerprint for quality consistency. In acute inflammatory models, the paw
edema of rats was induced by subcutaneous injection of carrageenan or
pro-inflammatory mediators, including histamine, serotonin, bradykinin, and
prostaglandin E(2) (PGE(2)) into the right hind paws of animals; while the ear
edema of mice was induced by applying arachidonic acid or
12-O-tetradecanoylphorbol 13-acetate (TPA) on the ear surface. In nociceptive
models, the tail-flick response induced by radiant heat stimulation was measured
and the numbers of abdominal writhing episodes of mice induced by
intraperitoneal injection of acetic acid were recorded. JCICM-6 orally
administered in a range of dosages from 0.438 g to 1.75 g/kg significantly and
dose-dependently suppressed the paw edema of rats induced by carrageenan or
various pro-inflammatory mediators and the ear edema of mice induced by
arachidonic acid or TPA. JCICM-6 also significantly prolonged the reaction time
of rats to radiant heat stimulation and reduced the numbers of writhing episodes
of mice. These results indicated that JCICM-6 possesses significant
anti-inflammatory and analgesic effects, which implies that it would be a
potential candidate for further investigation as a new anti-arthritic botanical
drug for humans.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16462027 [PubMed - indexed for MEDLINE]

54: Mutat Res. 2006 Apr 11;596(1-2):81-90. Epub 2006 Jan 30.

Inhibition of telomerase activity and induction of apoptosis by curcumin in
K-562 cells.

Chakraborty S, Ghosh U, Bhattacharyya NP, Bhattacharya RK, Roy M.

Environmental Carcinogenesis and Toxicology Department, Chittaranjan National
Cancer Institute, 37, SP Mukherjee Road, Kolkata 700026, India.

Telomerase, a reverse transcriptase that maintains telomere length, is highly
activated in tumor cells and practically absent in somatic cells and hence
considered a potential marker for tumorigenesis. A connection between telomerase
activity and resistance to apoptosis has been established. Telomerase,
therefore, has been proposed to represent a novel and potentially selective
target for cancer therapy. Several synthetic compounds have been developed in
recent years with a view to inhibit telomerase activity with telomere shortening
below a critical length resulting in apoptosis. Such compounds are always highly
toxic. Many plant-derived products act through the induction of apoptosis as a
mechanism to suppress carcinogenesis. Curcumin, a phenolic compound isolated
from the rhizome of the plant Curcuma longa Linn., has been reported to possess
anti-tumor, apoptotic and anti-angiogenic properties. Apoptosis has emerged as
the major mechanism by which anti-tumor agents eliminate pre-neoplastic cells or
cells progressed to malignancy. The present study was undertaken to examine the
mechanism of curcumin-induced apoptosis in human leukemia cell line K-562 with
particular emphasis on the role of curcumin on telomerase activity. Induction of
apoptosis by curcumin is initiated by the release of cytochrome c from
mitochondria into the cytosol, and evidenced by the increase in DNA content in
the sub-G1 region as obtained from FACS analysis. Apoptosis is mediated by the
activation of caspases 3 and 8, up-regulation of the apoptotic gene bax with
concomitant down-regulation of the anti-apoptotic gene bcl-2. Using TRAP assay
it has been observed that curcumin inhibits telomerase activity in a dose and
time-dependent manner, the inhibition being due to suppression of translocation
of telomerase reverse transcriptase (TERT), a catalytic subunit, from cytosol to
nucleus. Most significantly, the inhibition of telomerase activity by curcumin
correlates with several parameters of apoptosis. The results suggest that
telomerase status plays an important role in the induction of apoptosis in K-562
cells by curcumin.

PMID: 16445949 [PubMed - indexed for MEDLINE]

55: Arch Gerontol Geriatr. 2006 May-Jun;42(3):289-306. Epub 2006 Jan 26.

Menopause: a review on the role of oxygen stress and favorable effects of
dietary antioxidants.

Miquel J, Ramirez-Bosca A, Ramirez-Bosca JV, Alperi JD.

Department of Biotechnology, University of Alicante, San Vicente, Ap. 99,
E-03080 Alicante, Spain.

Menopause is often accompanied by hot flashes and degenerative processes such as
arteriosclerosis and atrophic changes of the skin that suggest an acceleration
of aging triggered by estrogen lack. Therefore, hormone replacement therapy
(HRT) has been considered the most suitable treatment for the above symptoms and
processes. However, because of the possible serious side effects of HRT
(especially the increased risk of thrombo-embolic accidents and breast cancer)
there is a growing demand for alternative treatments of the symptoms and
pathological processes associated with menopause. In agreement with the above,
we review research that supports the concept that oxygen stress contributes to
menopause and that some of its physiopathological effects may be prevented
and/or treated improving the antioxidant defense of menopausic and
postmenopausic women. Accordingly, a selection of micronutrients may be useful
as a dietary supplement for protection against the decline of physiological
functions caused by age-related oxygen stress. Since aging is accompanied by a
progressive oxidation of the physiological sulfur pool, we emphasize the role of
the vitamins B that help to maintain the GSH/GSSG ratio in its normal reduced
state. Nutritional supplements should also include the key antioxidant vitamins
C and E, as well as beta-carotene and the mineral micronutrients found in the
oxygen radical-detoxifying enzymes glutathione peroxidase and superoxide
dismutase. Moreover, the reviewed data suport the concept that other
antioxidants such as lipoic acid and the precursors of glutathione thioproline
(TP) and l-2-oxothiazolidine-4-carboxylic acid (OTC), as well as the soy
isoflavones and the "coantioxidants" of an hydroalcoholic extract of Curcuma
longa may help to prevent antioxidant deficiency with resulting protection of
mitochondria against premature oxidative damage with loss of ATP synthesis and
especialized cellular functions. Therefore, the administration under medical
advice of synergistic combinations of some of the above mentioned antioxidants
in the diet as well as topically (for skin protection) may have favorable
effects on the health and quality of life of women, especially of those who
cannot be treated with HR, suffer high levels of oxygen stress, and do not
consume a healthy diet that includes five daily rations of fresh fruit and
vegetables.

Publication Types:
Review

PMID: 16442644 [PubMed - indexed for MEDLINE]

56: Life Sci. 2006 Mar 27;78(18):2081-7. Epub 2006 Jan 18.

Multiple biological activities of curcumin: a short review.

Maheshwari RK, Singh AK, Gaddipati J, Srimal RC.

Department of Pathology, Uniformed Services University of the Life Sciences,
Center for Combat Casualty and Life Sustainment Research, Bethesda, Maryland
20814, USA. [email protected]

Turmeric (Curcuma longa rhizomes), commonly used as a spice is well documented
for its medicinal properties in Indian and Chinese systems of medicine. It has
been widely used for the treatment of several diseases. Epidemiological
observations, though inconclusive, are suggestive that turmeric consumption may
reduce the risk of some form of cancers and render other protective biological
effects in humans. These biological effects of turmeric have been attributed to
its constituent curcumin that has been widely studied for its anti-inflammatory,
anti-angiogenic, anti-oxidant, wound healing and anti-cancer effects. As a
result of extensive epidemiological, clinical, and animal studies several
molecular mechanisms are emerging that elucidate multiple biological effects of
curcumin. This review summarizes the most interesting in vitro and in vivo
studies on the biological effects of curcumin.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

PMID: 16413584 [PubMed - indexed for MEDLINE]

57: Phytother Res. 2006 Jan;20(1):79-81.

Inhibitory effect of Thai plant extracts on P-glycoprotein mediated efflux.

Junyaprasert VB, Soonthornchareonnon N, Thongpraditchote S, Murakami T, Takano
M.

Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447
Sri-Ayutthaya, Rajathavee, Bangkok 10400, Thailand. [email protected]

Curcuminoids from Curcuma longa L. and extracts of Psidium guajava L.,
Andrographis paniculata (Burm. f.) Nees, Phyllanthus emblica L. and Solanum
trilobatum L. were investigated for their inhibitory effect on P-glycoprotein
(P-gp) on the efflux transport of rhodamine 123 (Rho-123 ) in Caco-2 cells and
rat ileum. Of the five tested samples, curcuminoids and an extract of P. guajava
showed the highest inhibitory effect on P-gp mediated efflux of Rho-123 in
Caco-2 cells. Additionally, they were found to have equal potential in
inhibiting Rho-123 efflux transport from serosal to mucosal surfaces of the rat
ileum. Copyright 2006 John Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16397849 [PubMed - indexed for MEDLINE]

58: Plant Cell Rep. 2006 Mar;25(2):112-6. Epub 2006 Jan 6.

An efficient protocol for genetic transformation and shoot regeneration of
turmeric (Curcuma longa L.) via particle bombardment.

Shirgurkar MV, Naik VB, von Arnold S, Nadgauda RS, Clapham D.

Tissue Culture Pilot Plant, National Chemical Laboratory, Dr. Homi Bhabha Road,
Pashan, Pune 411008, India.

Turmeric (Curcuma longa L.) is an important spice crop plant that is sterile and
cannot be improved by conventional breeding. An efficient method for stable
transformation for turmeric, C. longa L., was developed using particle
bombardment. Callus cultures initiated from shoots were bombarded with gold
particles coated with plasmid pAHC25 containing the bar and gusA genes each
driven by the maize ubiquitin promoter. Transformants were selected on medium
containing glufosinate. Transgenic lines were established on selection medium
from 50% of the bombarded calluses. Transgenic shoots regenerated from these
were multiplied and stably transformed plantlets were produced. Polymerase chain
reaction (PCR) and histochemical GUS assay confirmed the stable transformation.
Transformed plantlets were resistant to glufosinate.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16397786 [PubMed - indexed for MEDLINE]

59: Ann N Y Acad Sci. 2005 Nov;1056:206-17.

Curcumin: getting back to the roots.

Shishodia S, Sethi G, Aggarwal BB.

Cytokine Research Laboratory, Department of Experimental Therapeutics, The
University of Texas M. D. Anderson Cancer Center, Box 143, 1515 Holcombe
Boulevard, Houston, TX 77030. [email protected]

The use of turmeric, derived from the root of the plant Curcuma longa, for
treatment of different inflammatory diseases has been described in Ayurveda and
in traditional Chinese medicine for thousands of years. The active component of
turmeric responsible for this activity, curcumin, was identified almost two
centuries ago. Modern science has revealed that curcumin mediates its effects by
modulation of several important molecular targets, including transcription
factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes
(e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g.,
cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors
(e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can
modulate the expression of these targets, curcumin is now being used to treat
cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases,
osteoporosis, Alzheimer's disease, psoriasis, and other pathologies.
Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of
ginger (Zingiber officinalis), exhibits a biologic activity profile similar to
that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of
curcuminoids prompt us to "get back to our roots."

PMID: 16387689 [PubMed - in process]

60: Eur J Med Chem. 2006 Feb;41(2):213-8. Epub 2006 Jan 4.

Alpha-glucosidase inhibition of natural curcuminoids and curcumin analogs.

Du ZY, Liu RR, Shao WY, Mao XP, Ma L, Gu LQ, Huang ZS, Chan AS.

School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou
510275, China.

Natural curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3)
isolated from Curcuma longa (turmeric), and synthetic curcumin analogs (A(1-7),
B(1-7), C(1-6) and D(1-7)) were evaluated in vitro for the alpha-glucosidase
inhibitory activity via UV and circular dichroism (CD) spectroscopy. The results
indicated that natural curcuminoid compound 3 showed a remarkable inhibitory
effect with IC(50) of 23.0 microM, and the synthetic compounds A(2), B(2), C(2)
and D(2) showed potent inhibitory effects with IC(50) of 2.8, 2.6, 1.6 and 8.2
microM, respectively. Kinetic study exhibited that the mechanism of
alpha-glucosidase inhibition of both 3 and C(2) was non-competitive. The
structure activity relationship revealed that the ortho dihydroxyl groups could
form a more tight interaction with alpha-glucosidase to exert more potential
inhibitory activities.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16387392 [PubMed - indexed for MEDLINE]

61: Cell Biol Int. 2006 Mar;30(3):221-6. Epub 2005 Dec 22.

Antiproliferation and apoptosis induced by curcumin in human ovarian cancer
cells.

Shi M, Cai Q, Yao L, Mao Y, Ming Y, Ouyang G.

Key Laboratory of China Education Ministry for Cell Biology and Tumor Cell
Engineering, School of Life Sciences, Xiamen University, Xiamen 361005, China.

Curcumin, an active ingredient from the rhizome of the plant, Curcuma longa, has
antioxidant, anti-inflammatory and anti-cancer activities. It has recently been
demonstrated that the chemopreventive activities of curcumin might be due to its
ability to inhibit cell growth and induce apoptosis. In the present study, we
have investigated the effects of curcumin on growth and apoptosis in the human
ovarian cancer cell line Ho-8910 by MTT assay, fluorescence microscopy, flow
cytometry and Western blotting. Our data revealed that curcumin could
significantly inhibit the growth and induce apoptosis in Ho-8910 cells. A
decrease in expression of Bcl-2, Bcl-X(L) and pro-caspase-3 was observed after
exposure to 40 microM curcumin, while the levels of p53 and Bax were increased
in the curcumin-treated cells. These activities may contribute to the
anticarcinogenic action of curcumin.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16376585 [PubMed - indexed for MEDLINE]

62: Biochem Biophys Res Commun. 2006 Feb 10;340(2):359-68. Epub 2005 Dec 13.

Curcumin induces growth-arrest and apoptosis in association with the inhibition
of constitutively active JAK-STAT pathway in T cell leukemia.

Rajasingh J, Raikwar HP, Muthian G, Johnson C, Bright JJ.

Department of Neurology, Vanderbilt University Medical Center, Nashville, TN
37212, USA.

Adult T cell leukemia is an aggressive and frequently fatal malignancy that
expressess constitutively activated growth-signaling pathways in association
with deregulated growth and resistance to apoptosis. Curcumin
(diferuloylmethane) is a naturally occurring yellow pigment, isolated from the
rhizomes of the plant Curcuma longa that has traditionally been used in the
treatment of injury and inflammation. But the effect and mechanism of action of
curcumin on T cell leukemia is not known. To investigate the antitumor activity
of curcumin in T cell leukemia, we examined its effect on constitutive
phosphorylation of JAK and STAT proteins, proliferation, and apoptosis in
HTLV-I-transformed T cell lines. HTLV-I-transformed T cell leukemia lines, MT-2,
HuT-102, and SLB-1, express constitutively phosphorylated JAK3, TYK2, STAT3, and
STAT5 signaling proteins. In vitro treatment with curcumin induced a
dose-dependent decrease in JAK and STAT phosphorylation resulting in the
induction of growth-arrest and apoptosis in T cell leukemia. The induction of
growth-arrest and apoptosis in association with the blockade of constitutively
active JAK-STAT pathway suggests this be a mechanism by which curcumin induces
antitumor activity in T cell leukemia.

Publication Types:
Research Support, N.I.H., Extramural

PMID: 16364242 [PubMed - indexed for MEDLINE]

63: Int J Food Sci Nutr. 2005 Sep;56(6):399-414.

Plant foods in the management of diabetes mellitus: spices as beneficial
antidiabetic food adjuncts.

Srinivasan K.

Department of Biochemistry & Nutrition, Central Food Technological Research
Institute, Mysore-570013, India.

Diet has been recognized as a corner stone in the management of diabetes
mellitus. Spices are the common dietary adjuncts that contribute to the taste
and flavour of foods. Besides, spices are also known to exert several beneficial
physiological effects including the antidiabetic influence. This review
considers all the available information from animal experimentation as well as
clinical trials where spices, their extracts or their active principles were
examined for treatment of diabetes. Among the spices, fenugreek seeds
(Trigonella foenumgraecum), garlic (Allium sativum), onion (Allium cepa), and
turmeric (Curcuma longa) have been experimentally documented to possess
antidiabetic potential. In a limited number of studies, cumin seeds (Cuminum
cyminum), ginger (Zingiber officinale), mustard (Brassica nigra), curry leaves
(Murraya koenigii) and coriander (Coriandrum sativum) have been reported to be
hypoglycaemic.

Publication Types:
Review

PMID: 16361181 [PubMed - indexed for MEDLINE]

64: Biol Pharm Bull. 2005 Dec;28(12):2220-4.

Curcuma longa extract protects against gastric ulcers by blocking H2 histamine
receptors.

Kim DC, Kim SH, Choi BH, Baek NI, Kim D, Kim MJ, Kim KT.

Division of Molecular and Life Science, SBD-NCRC, Pohang University of Science
and Technology, South Korea.

Curcuma longa has been commonly used as a traditional remedy for a variety of
symptoms such as inflammation, gastritis and gastric ulcer. When C. longa
extract was administered per os to pylori-ligated rat stomachs, it reduced
gastric acid secretion and protected against the formation of gastric mucosal
lesions. We therefore tested whether C. longa extract inhibits gastric ulcers by
blocking the H(2) histamine receptor. Dimaprit, a H(2) histamine receptor
agonist, induced intracellular cAMP production in U937 and HL-60 promyelocytes.
Pretreatment with C. longa extract significantly blocked dimaprit-induced cAMP
production in a concentration dependent manner, but had no effect on the
elevation of cAMP levels triggered by isoproterenol-induced beta(2)-adrenoceptor
activation in U937 cells. To identify the active component(s) of C. longa
extract, we sequentially fractionated it by extraction with ethyl acetate,
n-butanol and water. We found that the ethyl acetate extract showed the most
potent H(2)R antagonistic effect against dimaprit-induced cAMP production.
However, curcumin, a major component of C. longa extract, showed no H(2)R
blocking effect. C. longa ethanol extract and ethylacetate extract also blocked
the binding of [(3)H]-tiotidine to membrane receptors on HL-60 cells. These
findings suggest that the extract from C. longa specifically inhibits gastric
acid secretion by blocking H(2) histamine receptors in a competitive manner.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16327153 [PubMed - indexed for MEDLINE]

65: Phytother Res. 2005 Nov;19(11):988-91.

In vitro susceptibility of Helicobacter pylori to botanical extracts used
traditionally for the treatment of gastrointestinal disorders.

Mahady GB, Pendland SL, Stoia A, Hamill FA, Fabricant D, Dietz BM, Chadwick LR.

Program for Collaborative Research in the Pharmaceutical Sciences, University of
Illinois at Chicago, 833 S. Wood Street M/C 877, 60612, USA. [email protected]

The gram-negative bacterium Helicobacter pylori (HP), identified in 1982, is now
recognized as the primary etiological factor associated with the development of
gastritis and peptic ulcer disease. In addition, HP infections are also
associated with chronic gastritis, gastric carcinoma and primary gastric B-cell
lymphoma. For centuries, herbals have been used in traditional medicine to treat
a wide range of ailments, including gastrointestinal (GI) disorders such as
dyspepsia, gastritis and peptic ulcer disease (PUD). However, the mechanism of
action by which these botanicals exert their therapeutic effects has not been
completely elucidated. As part of an ongoing screening program, the study
assessed the in vitro susceptibility of 15 HP strains to botanical extracts,
which have a history of traditional use in the treatment of GI disorders.
Methanol extracts of Myristica fragrans (seed) had a MIC of 12.5 microg/mL;
Zingiber officinale (ginger rhizome/root) and Rosmarinus officinalis (rosemary
leaf) had an MIC of 25 microg/mL. Methanol extracts of botanicals with a MIC of
50 microg/mL included Achillea millefolium, Foeniculum vulgare (seed),
Passiflora incarnata (herb), Origanum majorana (herb) and a (1:1) combination of
Curcuma longa (root) and ginger rhizome. Botanical extracts with a MIC of 100
microg/mL included Carum carvi (seed), Elettaria cardamomum (seed), Gentiana
lutea (roots), Juniper communis (berry), Lavandula angustifolia (flowers),
Melissa officinalis (leaves), Mentha piperita (leaves) and Pimpinella anisum
(seed). Methanol extracts of Matricaria recutita (flowers) and Ginkgo biloba
(leaves) had a MIC > 100 microg/mL.

PMID: 16317658 [PubMed - indexed for MEDLINE]

66: Int J Low Extrem Wounds. 2005 Dec;4(4):205-13.

Turmeric (Curcuma longa) rhizome paste and honey show similar wound healing
potential: a preclinical study in rabbits.

Kundu S, Biswas TK, Das P, Kumar S, De DK.

Department of Veterinary Surgery and Radiology, West Bengal University of Animal
and Fishery Sciences, Kolkata, India. [email protected]

The potential efficacy of fresh turmeric (Curcuma longa) paste to heal wounds
was tested in a preclinical study in an animal model. Turmeric paste was
compared with honey as a topical medicament against a control on experimentally
created full-thickness circular wounds in 18 rabbits (Oryctolagous cuniculus).
Wound healing was assessed on the basis of physical, histomorphological, and
histochemical parameters on treatment days 0, 3, 7, and 14. Only tensile
strength was measured on day 14 of treatment. It was observed that the wound
healing was statistically significantly faster (P < .01) in both treatment
groups compared to the control group.

Publication Types:
Comparative Study

PMID: 16286372 [PubMed - indexed for MEDLINE]

67: J Agric Food Chem. 2005 Nov 16;53(23):9005-9.

Curcuma longa L. constituents inhibit sortase A and Staphylococcus aureus cell
adhesion to fibronectin.

Park BS, Kim JG, Kim MR, Lee SE, Takeoka GR, Oh KB, Kim JH.

School of Agricultural Biotechnology, Seoul National University, Seoul 151-742,
South Korea.

The inhibitory activity of Curcuma longa L. (turmeric) rhizome constituents
against sortase A, a bacterial surface protein anchoring transpeptidase, from
Staphylococcus aureus ATCC 6538p was evaluated. The activity of the isolated
compounds (1-4) was compared to that of the positive
control,p-hydroxymecuribenzoic acid (pHMB). The biologically active components
of C. longa rhizome were characterized by spectroscopic analysis as the
curcuminoids curcumin (1), demethoxycurcumin (2), and bisdemethoxycurcumin (3).
Curcumin was a potent inhibitor of sortase A, with an IC50 value of 13.8 +/- 0.7
microg/mL. Bisdemethoxycurcumin (IC50 = 31.9 +/- 1.2 microg/mL) and
demethoxycurcumin (IC50 = 23.8 +/- 0.6 microg/mL) were more effective than pHMB
(IC50 = 40.6 +/- 1.2 microg/mL). The three isolated compounds (1-3) showed no
growth inhibitory activity against S. aureus strain Newman, with minimum
inhibitory concentrations (MICs) greater than 200 microg/mL. Curcumin also
exhibited potent inhibitory activity against S. aureus cell adhesion to
fibronectin. The suppression of fibronectin-binding activity by curcumin
highlights its potential for the treatment of S. aureus infections via
inhibition of sortase activity. These results indicate that curcumin is a
possible candidate in the development of a bacterial sortase A inhibitor.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16277395 [PubMed - indexed for MEDLINE]

68: Life Sci. 2006 Feb 23;78(13):1419-32. Epub 2005 Nov 7.

Comparative screening of plant essential oils: phenylpropanoid moiety as basic
core for antiplatelet activity.

Tognolini M, Barocelli E, Ballabeni V, Bruni R, Bianchi A, Chiavarini M,
Impicciatore M.

Dipartimento di Scienze Farmacologiche, Biologiche e Chimiche Applicate,
Universita di Parma, Parco Area delle Scienze 27/A, 43100 Parma, Italy.

Essential oils extracted from different plants (Anthemis nobilis L., Artemisia
dracunculus L., Cannabis sativa L., Cupressus sempervirens L., Cymbopogon
citratus (DC.) Stapf., Curcuma longa L., Foeniculum vulgare L., Hypericum
perforatum L., Hyssopus officinalis L., Mentha spicata L., Monarda didyma L.,
Ocimum basilicum L., Ocotea quixos Kosterm., Origanum vulgare L., Pinus nigra
J.F. Arnold, Pinus silvestris L., Piper crassinervium Kunth., Rosmarinus
officinalis L., Salvia officinalis L., Salvia sclarea L., Santolina
chamaecyparissus L., Thymus vulgaris L., Zingiber officinaie L.) were screened
in guinea pig and rat plasma in order to assess antiplatelet activity and
inhibition of clot retraction. The oils were chemically analysed and a
relationship between components and ability to affect hemostasis was evidenced.
O. quixos, F. vulgaris, and A. dracunculus showed the highest antiplatelet
activity against ADP, Arachidonic Acid and the Thromboxane A2 agonist U46619
(IC50, 4-132 microg ml(-1)), and a good ability to destabilize clot retraction
(IC50, 19-180 microg ml(-1)). For these oils a significant correlation between
antiplatelet potency and phenylpropanoids content (54-86%) was evidenced thus
suggesting a key role for this moiety in the prevention of clot formation. These
findings provide the rationale to take in account the antiplatelet activity in
the pharmacological screening of natural products containing phenylpropanoids.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16274702 [PubMed - indexed for MEDLINE]

69: Life Sci. 2006 Mar 13;78(16):1884-91. Epub 2005 Nov 2.

Prevention of kainic acid-induced changes in nitric oxide level and neuronal
cell damage in the rat hippocampus by manganese complexes of curcumin and
diacetylcurcumin.

Sumanont Y, Murakami Y, Tohda M, Vajragupta O, Watanabe H, Matsumoto K.

Division of Medicinal Pharmacology, Institute of Natural Medicine, Toyama
Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.

Curcumin is a natural antioxidant isolated from the medicinal plant Curcuma
longa Linn. We previously reported that manganese complexes of curcumin (Cp-Mn)
and diacetylcurcumin (DiAc-Cp-Mn) exhibited potent superoxide dismutase
(SOD)-like activity in an in vitro assay. Nitric oxide (NO) is a free radial
playing a multifaceted role in the brain and its excessive production is known
to induce neurotoxicity. Here, we examined the in vivo effect of Cp-Mn and
DiAc-Cp-Mn on NO levels enhanced by kainic acid (KA) and L-arginine (L-Arg) in
the hippocampi of awake rats using a microdialysis technique. Injection of KA
(10 mg/kg, i.p.) and L-Arg (1000 mg/kg, i.p.) significantly increased the
concentration of NO and Cp-Mn and DiAc-Cp-Mn (50 mg/kg, i.p.) significantly
reversed the effects of KA and L-Arg without affecting the basal NO
concentration. Following KA-induced seizures, severe neuronal cell damage was
observed in the CA1 and CA3 subfields of hippocampal 3 days after KA
administration. Pretreatment with Cp-Mn and DiAc-Cp-Mn (50 mg/kg, i.p.)
significantly attenuated KA-induced neuronal cell death in both CA1 and CA3
regions of rat hippocampus compared with vehicle control, and Cp-Mn and
DiAc-Cp-Mn showed more potent neuroprotective effect than their parent
compounds, curcumin and diacetylcurcumin. These results suggest that Cp-Mn and
DiAc-Cp-Mn protect against KA-induced neuronal cell death by suppression of
KA-induced increase in NO levels probably by their NO scavenging activity and
antioxidative activity. Cp-Mn and DiAc-Cp-Mn have an advantage to be
neuroprotective agents in the treatment of acute brain pathologies associated
with NO-induced neurotoxicity and oxidative stress-induced neuronal damage such
as epilepsy, stroke and traumatic brain injury.

PMID: 16266725 [PubMed - indexed for MEDLINE]

70: J Food Prot. 2005 Oct;68(10):2054-8.

Antimicrobial effect of Thai spices against Listeria monocytogenes and
Salmonella typhimurium DT104.

Thongson C, Davidson PM, Mahakarnchanakul W, Vibulsresth P.

Department of Food Science and Technology, 2605 River Drive, University of
Tennessee, Knoxville, Tennessee 37996-4591, USA.

The objective of this study was to determine the potential antimicrobial
activity of extracts and essential oils of spices from Thailand against
foodborne pathogenic bacteria. The antimicrobial efficacy of ginger (Zingiber
officinale), fingerroot (Boesenbergia pandurata), and turmeric (Curcuma longa)
was evaluated against five strains of Listeria monocytogenes and four strains of
Salmonella enterica ssp. enterica serovar Typhimurium DT104. Antimicrobial
activity was investigated in microbiological media by using an agar dilution
assay and enumeration over time and a model food system, apple juice, by
monitoring growth over time. In the agar dilution assay, water extracts of the
three spices had no effect on L. monocytogenes. Similarly, 50% ethanol extracts
of ginger or turmeric had no effect. In contrast, ethanolic fingerroot extracts
at 5 to 10% (vol/ vol) inhibited most L. monocytogenes strains for 24 h in the
agar dilution assay. Commercial essential oils (EO) of ginger or turmeric
inhibited all L. monocytogenes at < or = 0.6 or < or = 10%, respectively.
Fingerroot EO inhibited all strains at < or = 0.4%. In the enumeration-over-time
assay, a 5% fingerroot ethanol extract reduced ca. 4 log CFU/ml Listeria by
around 2 log in 24 h while 10% inactivated the microorganism in 9 h. Fingerroot
EO at 0.2% inactivated 4 log CFU/ml L. monocytogenes in 6 to 9 h. Neither
extracts nor commercial EO had any effect on Salmonella Typhimurium DT 104 with
the exception of fingerroot EO, which inhibited all strains at < or = 0.7%.
Addition of 0.2% fingerroot EO to apple juice reduced 4 log of L. monocytogenes
Scott A and both strains of Salmonella Typhimurium to an undetectable level
within 1 to 2 days. It was concluded that fingerroot EO and extract have
potential for inhibiting pathogens in food systems.

PMID: 16245707 [PubMed - indexed for MEDLINE]

71: Arterioscler Thromb Vasc Biol. 2006 Jan;26(1):85-90. Epub 2005 Oct 20.

Curcumin inhibits platelet-derived growth factor-stimulated vascular smooth
muscle cell function and injury-induced neointima formation.

Yang X, Thomas DP, Zhang X, Culver BW, Alexander BM, Murdoch WJ, Rao MN, Tulis
DA, Ren J, Sreejayan N.

Division of Pharmaceutical Sciences, Center for Cardiovascular Research and
Alternative Medicine, University of Wyoming, Laramie, WY 82071-3375, USA.

OBJECTIVE: Vascular smooth muscle cell (VSMC) migration, proliferation, and
collagen synthesis are key events involved in the pathogenesis of cardiovascular
disease. Growth factors, such as platelet-derived growth factor (PDGF) and
fibroblast growth factor, released during vascular injury plays a pivotal role
in regulating these events. Curcumin (diferuloyl methane), a major component of
the spice turmeric (Curcuma longa), has been shown recently to have beneficial
effects in chronic conditions, such as inflammation, cancer, cystic fibrosis,
and Alzheimer's disease. The objective of this study was to investigate the
ability of curcumin to inhibit PDGF-stimulated migration, proliferation, and
collagen synthesis in cultured VSMCs and neointima formation after carotid
artery injury in rats. METHODS AND RESULTS: Curcumin (1 to 25 microM) produced a
concentration-dependent inhibition of PDGF-elicited VSMC migration,
proliferation, and collagen synthesis assessed by chemotaxis, [3H]thymidine
incorporation, and [3H]-L-proline incorporation, respectively. Curcumin blocked
PDGF-induced VSMC actin-cytoskeleton reorganization, attenuated PDGF signal
transduction, and inhibited the binding of PDGF to its receptors. Carotid artery
neointima formation was significantly attenuated by perivascular curcumin
compared with vehicle controls 14 days after injury, characterized by reduced
DNA synthesis, collagen synthesis, and PDGF receptor phosphorylation.
CONCLUSIONS: These data suggest that curcumin is a potent inhibitor of key
PDGF-stimulated VSMC functions and may play a critical role in regulating these
events after vascular injury.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

PMID: 16239599 [PubMed - indexed for MEDLINE]

72: Asian Pac J Cancer Prev. 2005 Jul-Sep;6(3):353-8.

Growth inhibitory activities of crude extracts obtained from herbal plants in
the Ryukyu Islands on several human colon carcinoma cell lines.

Kaneshiro T, Suzui M, Takamatsu R, Murakami A, Ohigashi H, Fujino T, Yoshimi N.

Tumor Pathology, University of the Ryukyus Faculty of Medicine, 207 Uehara
Nishihara-cho, Okinawa 903-0215, Japan. [email protected]

There is increasing interest in the use of herbs for the treatment of human
diseases including cancer. Therefore, the purpose of this study was to determine
whether crude extracts obtained from 44 herbal plants in the Ryukyu Islands
might contain components capable of inhibiting the growth of a variety of human
colon carcinoma cell lines. Leaves, roots and other parts of the plants were
extracted with chloroform, and the crude extracts were dissolved in
dimethylsulfoxide and used for the experiments. Extracts of Hemerocallis fulva,
Ipomoea batatas, Curcuma longa, and Nasturium officinale caused marked
dose-dependent growth inhibition, with IC(50) values in the range of 10-80
mug/ml. With the HCT116 cell line, the extracts of Hemerocallis fulva and
Ipomoea batatas induced G1 cell cycle arrest after 48 h of treatment. In
addition, we found that extracts of Curcuma longa, and Nasturium officinale
induced apoptosis in these cells after 48 h of treatment. The present studies
are the first systematic examination of the growth inhibitory effects of crude
extracts obtained from herbal plants in the Ryukyu Islands. The findings provide
evidence that several plants in the Ryukyu Islands contain components that may
have anticancer activity.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16235999 [PubMed - indexed for MEDLINE]

73: Pharmacol Biochem Behav. 2005 Sep;82(1):200-6.

Antidepressant effects of curcumin in the forced swim test and olfactory
bulbectomy models of depression in rats.

Xu Y, Ku BS, Yao HY, Lin YH, Ma X, Zhang YH, Li XJ.

Department of Pharmacology, School of Basic Medical Science, Peking University,
China.

Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese
medicinal formula, which has been used to effectively manage stress and
depression-related disorders in China. Curcumin is the active component of
curcuma longa, and we hypothesized that curcumin would have an influence on
depressive-like behaviors. The purpose of the present study was to confirm the
putative antidepressant effect of chronic administrations of curcumin (1.25,
2.5, 5 and 10 mg/kg, p.o.) in the forced swimming test and bilateral olfactory
bulbectomy (OB) models of depression in rats. In the first study, chronic
treatment with curcumin (14 days) reduced the immobility time in the forced
swimming test. In the second experiment, curcumin reversed the OB-induced
behavioral abnormalities such as hyperactivity in the open field, as well as
deficits in step-down passive avoidance. In addition, OB-induced low levels of
serotonin (5-HT), noradrenaline (NA), high 5-hydroxyindoleacetic acid (5-HIAA)
and 4-dihydroxyphenylacetic acid (DOPAC) in the hippocampus were observed, and
were completely reversed by curcumin administration. A slight decrease in 5-HT,
NA and dopamine (DA) levels was found in the frontal cortex of OB rats which was
also reversed by curcumin treatment. These results confirm the antidepressant
effects of curcumin in the forced swim and the OB models of depression in rats,
and suggest that these antidepressant effects may be mediated by actions in the
central monoaminergic neurotransmitter systems.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16171853 [PubMed - indexed for MEDLINE]

74: Phytother Res. 2005 Jul;19(7):599-604.

Antibacterial activity of Curcuma longa L. against methicillin-resistant
Staphylococcus aureus.

Kim KJ, Yu HH, Cha JD, Seo SJ, Choi NY, You YO.

Department of Oral Microbiology, School of Dentistry and WBMI, Wonkwang
University, Iksan, South Korea.

Methicillin-resistant Staphylococcus aureus (MRSA) has been emerging worldwide
as one of the most important hospital and community pathogens. Therefore, new
agents are needed to treat MRSA associated infections. The present study
investigated the antimicrobial activity of ethyl acetate, methanol and water
extracts of Curcuma longa L. (C. longa) against MRSA. The ethyl acetate extract
of C. longa demonstrated a higher antibacterial activity than the methanol
extract or water extract. Since the ethyl acetate extract was more active than
the other extracts, the study examined whether the ethyl acetate extract could
restore the antibacterial activity of beta-lactams and alter the MRSA invasion
of human mucosal fibroblasts (HMFs). In the checkerboard test, the ethyl acetate
extract of C. longa markedly lowered the MICs of ampicillin and oxacillin
against MRSA. In the bacterial invasion assay, MRSA intracellular invasion was
significantly decreased in the presence of 0.125-2 mg/mL of C. longa extract
compared with the control group. These results suggest that the ethyl acetate
extract of C. longa may have antibacterial activity and the potential to restore
the effectiveness of beta-lactams against MRSA, and inhibit the MRSA invasion of
HMFs.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16161063 [PubMed - indexed for MEDLINE]

75: J Med Food. 2005 Summer;8(2):256-60.

Comparative effects of curcumin and its analog on alcohol- and polyunsaturated
fatty acid-induced alterations in circulatory lipid profiles.

Rukkumani R, Aruna K, Varma PS, Rajasekaran KN, Menon VP.

Department of Biochemistry, Faculty of Science, Annamalai University,
Annamalainagar, Tamil Nadu, India.

Excessive alcohol intake induces hyperlipidemia. Studies suggest that natural
principles and their analogs are known to possess anti-hyperlipidemic
properties. In the present work we tested the effect of curcumin, an active
principle of turmeric (Curcuma longa), and a curcumin analog on alcohol- and
thermally oxidized polyunsaturated fatty acid (deltaPUFA)- induced
hyperlipidemia. Male albino Wistar rats were used for the experimental study.
Anti-hyperlipidemic activity of curcumin and curcumin analog was evaluated by
analyzing the levels of cholesterol, triglycerides (TGs), phospholipids (PLs),
and free fatty acids (FFAs). The results showed that the levels of cholesterol,
TGs, PLs, and FFAs were increased significantly in alcohol-, deltaPUFA-, and
alcohol + deltaPUFA-treated groups, which were brought down significantly on
treatment with either of the curcuminoids. Curcumin analog treatment was found
to be more effective than curcumin treatment. From the results obtained, we
conclude that both curcumin and its analog effectively protect the system
against alcohol- and deltaPUFA-induced hyperlipidemia and are possible
candidates for the treatment of hyperlipidemia.

Publication Types:
Comparative Study

PMID: 16117621 [PubMed - indexed for MEDLINE]

76: Bioresour Technol. 2006 Aug;97(12):1372-6. Epub 2005 Aug 19.

Antiplatelet property of Curcuma longa L. rhizome-derived ar-turmerone.

Lee HS.

Faculty of Applied Biotechnology, Research Center for Industrial Development of
Biofood Materials, College of Agriculture, Chonbuk National University, Chonju
561-756, Republic of Korea. [email protected]

The antiplatelet activities of Curcuma longa L. rhizome-derived materials were
measured using a platelet aggregometer and compared with those of aspirin as
antiplatelet agent. The active constituent from the rhizome of Curcuma longa L.
was isolated and characterized as ar-turmerone by various spectral analyses. At
50% inhibitory concentration (IC50) value, ar-turmerone was effective in
inhibiting platelet aggregation induced by collagen (IC50, 14.4 microM) and
arachidonic acid (IC50, 43.6 microM). However, ar-turmerone had no effect on
platelet activating factor or thrombin induced platelet aggregation. In
comparison, ar-turmerone was significantly more potent platelet inhibitor than
aspirin against platelet aggregation induced by collagen. These results
suggested that ar-turmerone could be useful as a lead compound for inhibiting
platelet aggregation induced by collagen and arachidonic acid.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16112857 [PubMed - indexed for MEDLINE]

77: Phytother Res. 2005 May;19(5):409-15.

Effect of Dianex, a herbal formulation on experimentally induced diabetes
mellitus.

Mutalik S, Chetana M, Sulochana B, Devi PU, Udupa N.

College of Pharmaceutical Sciences, Manipal, Karnataka, India.

Dianex, a polyherbal formulation consisting of the aqueous extracts of Gymnema
sylvestre, Eugenia jambolana, Momordica charantia Azadirachta indica, Cassia
auriculata, Aegle marmelose, Withania somnifera and Curcuma longa was screened
for hypoglycemic activity in normal and streptozotocin induced diabetic mice.
Dianex was administered in different doses of 100-500 mg/kg/day orally in acute
(6 h) and long-term (6 weeks) studies. Blood glucose levels were checked 2-6 h
after treatment in acute studies and every 2 weeks in long-term studies. Body
weight was recorded on the first and final day of the treatment in the long-term
studies with diabetic mice. After 6 weeks, high-density lipoprotein,
triglycerides, total cholesterol, alanine transaminase (ALT), aspertate
transaminase (AST), urea and creatinine were estimated in serum of the diabetic
mice. Glycogen and total protein levels were estimated in the liver. Also, the
liver and pancreas was subjected to histological examination. Oral glucose
tolerance and in vitro free radical scavenging activity was also studied.Dianex
produced significant (p<0.05) hypoglycemic activity at 250-500 mg/kg doses in
both normal and diabetic mice in acute and long-term studies. The body weight of
diabetic mice significantly (p<0.05) increased with all tested doses of Dianex.
The elevated triglycerides, cholesterol, ALT, AST, urea and creatinine levels in
diabetic mice were significantly (p<0.05) reduced at the doses of 250 and 500
mg/kg. The liver glycogen and protein levels were both significantly (p<0.05)
increased in diabetic mice at 250 and 500 mg/kg doses. Dianex increased the
glucose tolerance significantly (p<0.05) in both normal and diabetic mice at all
the doses tested. Histopathological examination showed that the formulation
decreased streptozotocin induced injury to the tissues at all the doses tested.
It produced significant (p<0.05) free radical scavenging activity against ABTS+,
DPPH and hydroxyl free radicals at the concentrations ranging between 10-1000
microg/ml.Thus, in the present study, Dianex produced significant hypoglycemic
activity in both normal and diabetic animals. It also reversed other diabetic
complications in diabetic mice at 250 and 500 mg/kg doses. In our earlier study,
Dianex was well tolerated in laboratory animals at higher doses (upto 10 g/kg in
mice, acute toxicity; up to 2.5 g/kg in rats, subacute toxicity studies for 30
days) without exhibiting any toxic manifestation. Hence, Dianex may be useful in
the treatment of diabetes mellitus. Copyright (c) 2005 John Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16106394 [PubMed - indexed for MEDLINE]

78: Exp Brain Res. 2005 Dec;167(4):641-8. Epub 2005 Aug 3.

Curcumin treatment protects rat retinal neurons against excitotoxicity: effect
on N-methyl-D: -aspartate-induced intracellular Ca(2+) increase.

Matteucci A, Frank C, Domenici MR, Balduzzi M, Paradisi S, Carnovale-Scalzo G,
Scorcia G, Malchiodi-Albedi F.

Department of Cell Biology and Neuroscience, Istituto Superiore di Sanita, Viale
Regina Elena 299, 00161 Roma, Italy.

Curcumin, an extract from the plant Curcuma longa with well-known antioxidant
and anti-inflammatory activities, was tested as protective agent against
excitotoxicity in rat retinal cultures. A 24 h-treatment with curcumin reduced
N-methyl-D: -aspartate (NMDA)-mediated excitotoxic cell damage, estimated as
decrease of cell viability and increase in apoptosis. The protection was
associated with decrease of NMDA receptor-mediated Ca(2+) rise and reduction in
the level of phosphorylated NR1 subunit of the NMDA receptor. These results
enlighten a new pharmacological action of the plant extract, possibly mediated
by a modulation of NMDA receptor activity.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16078027 [PubMed - indexed for MEDLINE]

79: Ann N Y Acad Sci. 2005 Jun;1043:440-51.

Protective role of antioxidative food factors in oxidative stress caused by
hyperglycemia.

Osawa T, Kato Y.

Nagoya University Graduate School of Bioagricultural Sciences, Chikusa, Nagoya
464-8601, Japan. [email protected]

Hyperglycemia causes the autoxidation of glucose, glycation of proteins, and the
activation of polyol metabolism. These changes accelerate generation of reactive
oxygen species (ROS) and increases in oxidative chemical modification of lipids,
DNA, and proteins in various tissues. Oxidative stress may play an important
role in the development of complications in diabetes such as lens cataracts,
nephropathy, and neuropathy. Glycation reactions, especially Maillard reactions,
occur in vivo as well as in vitro and are associated with the chronic
complications of diabetes mellitus and aging and age-related diseases by
increases in oxidative chemical modification of lipids, DNA, and proteins. In
particular, long-lived proteins such as lens crystallines, collagens, and
hemoglobin may react with reducing sugars to form advanced glycation end
products (AGEs). Recently, we found a novel type of AGE, named MRX, and we found
that MRX is a good biomarker for detecting oxidative stress produced during
Maillard reaction. We also examined in detail the role of lipid peroxidation
reaction in hyperglycemia and found that hexanoyl modification formed by the
reaction of oxidized lipids and proteins must be important for oxidative stress.
Detailed analyses of the formation mechanism of hexanoyl lysine (HEL) moiety in
proteins were conducted, and excretion of HEL into urine was quantified by using
LC/MS/MS. Macrophages and neutrophils play an important role in oxidative stress
during hyperglycemia, and we determined that oxidatively modified tyrosines are
a good biomarker for formation of oxidative stress at an early stage.
Immunochemical analyses by application of monoclonal antibodies specific to
lipid hydroperoxide-modified proteins produced by polyunsaturated fatty acids
including docosahexaenoic acid (DHA) in oxidative stress caused by hyperglycemia
were conducted, and the relationship between glycation and lipid peroxidation
reactions both by chemical and immunochemical approaches are discussed.
Recently, we put much more focus on dietary antioxidants for prevention of
diabetic complications. Curcuminoids, the main yellow pigments in Curcuma longa
(turmeric), have been used widely and for a long time in the treatment of sprain
and inflammation in indigenous medicine. Curcumin is the main component of
turmeric, and two minor components are also present as the curcuminoids.
Curcuminoids possess antioxidant activity. Protective effects of curcumin (U1)
and one of its major metabolites, tetrahydrocurcumin (THU1), have been examined
for development of diabetic cataract in 25% galactose-fed SD rats. Through
detailed examination of protective mechanisms of THU1, it was found that THU1
showed that scavenger ROS not only formed during hyperglycemia, but also induced
antioxidative enzymes including detoxification enzymes such as glutathine
S-transferase. THU1 also showed significant increase of glutathione
concentration in the cultured rat lens. Glutathione (gamma-glutamylcysteinyl
glycine [GSH]) is thought to be an important factor in cellular function and
defense against oxidative stress, and we found that dietary GSH suppresses
oxidative stress in vivo in prevention of diabetic complications such as
diabetic nephropathy and neuropathy.

Publication Types:
Review

PMID: 16037265 [PubMed - indexed for MEDLINE]

80: Nat Prod Res. 2005 Sep;19(6):567-71.

In vitro enzyme inhibition activities of crude ethanolic extracts derived from
medicinal plants of Pakistan.

Khattak S, Saeed-Ur-Rehman, Shah HU, Khan T, Ahmad M.

Department of Chemistry, University of Peshawar, Peshawar - 25120, Pakistan.
[email protected]

Twenty two crude ethanolic extracts from 14 indigenous medicinal plants were
subjected to enzyme inhibition screening against acetylcholinesterase (AChE),
butyrylcholinesterase (BChE) and lipoxygenase enzymes (LO). Three extracts
showed activity against AChE, nine extracts were found to be active against BChE
and four extracts inhibited the enzyme LO. The most significant inhibition
activities (> or =50%) were found in extracts derived from Aloe vera (leaves),
Alpinia galanga (rhizome), Curcuma longa (rhizome), Cymbopogon citratus
(leaves), Ocimum americanum (leaves), Ocimum americanum (stem) and Withania
somnifera (roots).

Publication Types:
In Vitro

PMID: 16010821 [PubMed - indexed for MEDLINE]

81: Fitoterapia. 2005 Sep;76(6):549-55.

Chemopreventive effects of embelin and curcumin against
N-nitrosodiethylamine/phenobarbital-induced hepatocarcinogenesis in Wistar rats.

Sreepriya M, Bali G.

Department of Microbiology and Biotechnology, Jnana Bharti Campus, Bangalore
University, Bangalore 560 056, Karnataka, India. [email protected]

The effects of embelin (50 mg/kg/day), a benzoquinone derivative of Embelia
ribes, and the effects of curcumin (100 mg/kg/day), the active principle of
Curcuma longa, against N-nitrosodiethylamine (DENA)-initiated and phenobarbital
(PB)-promoted hepatocarcinogenesis were studied in Wistar rats. They were able
to prevent the induction of hepatic hyper plastic nodules, body weight loss,
increase in the levels of hepatic diagnostic markers, and hypoproteinemia
induced by DENA/PB treatment. Hence, results of our study suggest the possible
chemopreventive effects of embelin (EMB) and curcumin (CUR) against
DENA/PB-induced hepatocarcinogenesis in Wistar rats.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16009505 [PubMed - indexed for MEDLINE]

82: Phytomedicine. 2005 Jun;12(6-7):445-52.

The effect of turmeric extracts on inflammatory mediator production.

Lantz RC, Chen GJ, Solyom AM, Jolad SD, Timmermann BN.

Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ, USA.
[email protected]

Major compounds of several commonly used botanicals, including turmeric, have
been purported to have anti-inflammatory actions. In order to test the
anti-inflammatory activity of compounds isolated from rhizomes of Curcuma longa
L. (Zingiberaceae), we have established an in vitro test system. HL-60 cells
were differentiated and exposed to lipopolysaccharide (LPS) from Escherichia
coli (1 microg/ml) in the presence or absence of botanical compounds for 24 h.
Supernatants were collected and analyzed for the production of tumor necrosis
factor alpha (TNF-alpha) and prostaglandin E2 (PGE2) using standard ELISA
assays. Water-soluble extracts were not cytotoxic and did not exhibit biological
activity. Organic extracts of turmeric were cytotoxic only at concentrations
above 50 microg/ml. Crude organic extracts of turmeric were capable of
inhibiting LPS-induced TNF-alpha (IC50 value = 15.2 microg/ml) and PGE2 (IC50
value = 0.92 microg/ml) production. Purified curcumin was more active than
either demethoxy- or bisdemethoxycurcumin. Fractions and subfractions of
turmeric extracts collected via preparative HPLC had differing biological
activity, ranging from no activity to IC50 values of < 1 microg/ml. For some
fractions, subfractionation resulted in a loss of activity, indicating
interaction of the compounds within the fraction to produce an anti-inflammatory
effect. A combination of several of the fractions that contain the turmeric oils
was more effective than the curcuminoids at inhibiting PGE2. While curcumin
inhibited COX-2 expression, turmeric oils had no effect on levels of COX-2 mRNA.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

PMID: 16008121 [PubMed - indexed for MEDLINE]

83: Eur J Pharmacol. 2005 Jul 25;518(1):40-6.

The effects of curcumin on depressive-like behaviors in mice.

Xu Y, Ku BS, Yao HY, Lin YH, Ma X, Zhang YH, Li XJ.

Department of Pharmacology, School of Basic Medical Science, Peking University,
38 Xueyuan Road, Beijing, 100083, PR China.

Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese
medicinal formula, which has been used effectively to treat depression-related
diseases in China. There is no information available about the antidepressant
activity of curcumin, the active component of curcuma longa. In the present
study, we analyzed the effects of curcumin on depressive-like behaviors in mice,
using two animal models of depression. Our results showed that curcumin
treatment at 5 and 10 mg/kg (p.o.) significantly reduced the duration of
immobility in both the tail suspension and forced swimming tests. These doses
that affected the immobile response did not affect locomotor activity. In
addition, the neurochemical assays showed that curcumin produced a marked
increase of serotonin and noradrenaline levels at 10 mg/kg in both the frontal
cortex and hippocampus. Dopamine levels were also increased in the frontal
cortex and the striatum. Moreover, curcumin was found to inhibit monoamine
oxidase activity in the mouse brain. These findings suggest that the
antidepressant-like effects of curcumin may involve the central monoaminergic
neurotransmitter systems.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 15987635 [PubMed - indexed for MEDLINE]

84: Ann N Y Acad Sci. 2005 May;1042:372-8.

Curcumin inhibits ROS formation and apoptosis in methylglyoxal-treated human
hepatoma G2 cells.

Chan WH, Wu HJ, Hsuuw YD.

Department of Bioscience Technology, Chung Yuan Christian University, Chung Li,
Taiwan 32023. [email protected]

Methylglyoxal (MG) is a reactive dicarbonyl compound endogenously produced
mainly from glycolytic intermediates. Elevated MG levels in diabetes patients
are believed to contribute to diabetic complications. MG is cytotoxic through
induction of apoptosis. Curcumin, the yellow pigment of Curcuma longa, is known
to have antioxidant and anti-inflammatory properties. In the present study, we
investigated the effect of curcumin on MG-induced apoptotic events in human
hepatoma G2 cells. We report that curcumin prevented MG-induced cell death and
apoptotic biochemical changes such as mitochondrial release of cytochrome c,
caspase-3 activation, and cleavage of PARP (poly [ADP-ribose] polymerase). Using
the cell permeable dye 2',7'-dichlorofluorescein diacetate (DCF-DA) as an
indicator of reactive oxygen species (ROS) generation, we found that curcumin
abolished MG-stimulated intracellular oxidative stress. The results demonstrate
that curcumin significantly attenuates MG-induced ROS formation, and suggest
that ROS triggers cytochrome c release, caspase activation, and subsequent
apoptotic biochemical changes.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15965083 [PubMed - indexed for MEDLINE]

85: Life Sci. 2005 Jul 8;77(8):837-57. Epub 2005 Apr 14.

Antiatherosclerotic effects of dietary supplementations of garlic and turmeric:
Restoration of endothelial function in rats.

Zahid Ashraf M, Hussain ME, Fahim M.

Department of Physiology, V. P. Chest Institute, University of Delhi, Delhi-110
007, India.

Protections of endothelial integrity by elimination of certain risk have proven
to be effective in maintaining hemostasis and in slowing the progress of the
cardiovascular disease. Indigenous drugs are the natural source of protection
against these disorders, which can be used more effectively by the knowledge of
their active ingredients as well as by their mechanism of action. Most prominent
among these drugs are garlic, [Alium sativum L., Family: Liliaceae, Bulbs] and
turmeric [Curcuma longa L., Family: Zingiberaceae, Rhizomes]; commonly used
Indian traditional spices. In the present study, we examined the
atheroscleroprotective potential of diet supplementation of garlic and turmeric
by measuring serum lipid profile, changes in cardiovascular parameters i.e.
arterial blood pressure, electrocardiogram and heart rate. We further tried to
elucidate the mechanism of restoration of endothelial function and the role of
endothelium-derived factors mainly, nitric oxide (NO) and cycloxygenase derived
contracting factors. A notable restoration of arterial blood pressure was seen
in animals on garlic and turmeric supplemented diet. Animals on supplemented
diet showed a significantly enhanced vasorelaxant response to adenosine,
acetylcholine, isoproterenol and contractile effect of 5-hyderoxytryptamine was
significantly attenuated. Inhibition of these responses by L-NMMA was smaller in
tissues from herbal treated animals. Incubation of tissues with L-arginine
(10(-5) M) resulted in a significant reversal of L-NMMA induced inhibition of
endothelium-mediated relaxation, which appeared to be pronounced in rings from
animals supplemented with herbs as compared to hypercholesterolemic animals.
Addition of indomethacin (10(-5) M) augmented the relaxation in all the groups
of animals. The present study demonstrated that garlic and turmeric are potent
vasorelaxants as well as reduce the atherogenic properties of cholesterol.
Whether combination of these vasodilators in cardiovascular disorders with
increased peripheral vascular resistance remains to be determined.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15964306 [PubMed - indexed for MEDLINE]

86: Biol Chem. 2005 May;386(5):481-90.

The anti-inflammatory compound curcumin inhibits Neisseria gonorrhoeae-induced
NF-kappaB signaling, release of pro-inflammatory cytokines/chemokines and
attenuates adhesion in late infection.

Wessler S, Muenzner P, Meyer TF, Naumann M.

Paul-Ehrlich-Institute, D-63225 Langen, Germany.

Neisseria gonorrhoeae (Ngo) is a Gram-negative pathogenic bacterium responsible
for an array of diseases ranging from urethritis to disseminated gonococcal
infections. Early events in the establishment of infection involve interactions
between Ngo and the mucosal epithelium, which induce a local inflammatory
response. Here we analyzed the molecular mechanism involved in the Ngo-induced
induction of the proinflammatory cytokines tumor necrosis factor alpha
(TNFalpha), interleukin-6 (IL-6), and IL-8. We identified the immediate early
response transcription factor nuclear factor kappaB (NF-kappaB) as a key
molecule for the induction of cytokine release. Ngo-induced activation of direct
upstream signaling molecules was demonstrated for IkappaB kinase alpha and beta
(IKKalpha and IKKbeta) by phosphorylation of IkappaBalpha as a substrate and IKK
autophosphorylation. Using dominant negative cDNAs encoding kinase-dead
IKKalpha, IKKbeta, and NF-kappaB-inducing kinase (NIK), Ngo-induced NF-kappaB
activity was significantly inhibited. Curcumin, the yellow pigment derived from
Curcuma longa, inhibited IKKalpha, IKKbeta and NIK, indicating its strong
potential to block NF-kappaB-mediated cytokine release and the innate immune
response. In addition to the inhibition of Ngo-induced signaling, curcumin
treatment of cells completely abolished the adherence of bacteria to cells in
late infection, underlining the high potential of curcumin as an anti-microbial
compound without cytotoxic side effects.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15927892 [PubMed - indexed for MEDLINE]

87: Anal Biochem. 2005 Jun 15;341(2):316-25.

Screening of plants containing Naja naja siamensis cobra venom inhibitory
activity using modified ELISA technique.

Daduang S, Sattayasai N, Sattayasai J, Tophrom P, Thammathaworn A, Chaveerach A,
Konkchaiyaphum M.

Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen
40002, Thailand. [email protected]

Enzyme-linked immunosorbent assay (ELISA) has been modified for screening plants
with antagonistic activity to Naja naja siamensis cobra venom. Aqueous extracts
from plants were investigated for their inhibitory effects on the binding of
anti-cobra venom antibody to antigen, cobra venom, fixed onto 96-well microtiter
plates. Ingredients in extracts were allowed to react with immobilized venom
before the subsequent addition of antivenom antibody. Venom components affected
by exposure to the extracts, unable to interact with their specific antibody,
were predicted to be unable to bind to their native destinations or natural
receptors. Curcuma cf. zedoaria, an old Thai medicinal plant, showed clear
inhibitory activity in the ELISA test. Neurotoxin and protein degradative
enzymes, major components in venom, were identified as targets of this extract
in Western immunoblotting analysis. Ingredients in the extract showed high
affinity to the toxin in competition assay by immunoprecipitation. The extract
attenuated toxin activity by extending contraction time of diaphragm muscle
after envenomation and had a potency to protect cellular proteins from venom
degradative enzymes. Curcuma parviflora, with less activity in ELISA, exhibited
acceptable results in two experiments but negative results in two experiments,
whereas Curcuma longa, having low activity in the ELISA test, never showed any
favorable results. Screening of 36 samples could classify plants into an
inhibition range of 0 to 86%. This modified ELISA is recommended as a
preliminary screening method for inhibitors with a large number of samples.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15907878 [PubMed - indexed for MEDLINE]

88: J Pharm Biomed Anal. 2005 Jun 1;38(1):133-8. Epub 2005 Jan 12.

Application of capillary zone electrophoresis in the separation and
determination of the curcuminoids in urine.

Yuan K, Weng Q, Zhang H, Xiong J, Xu G.

National Chromatographic R.&A. Center, Dalian Institute of Chemical Physics,
Chinese Academy of Sciences, Dalian 116011, PR China.

The major components of the plant curcuma longa are the curcuminoids that
include curcumin, demethoxycurcumin and bisdemethoxycurcumin. It has been
reported the curcuminoids have some important activities. A new CZE method with
diode array detection has been developed for the separation and determination of
the curcumin, demethoxycurcumin and bisdemethoxycurcumin. Three curcuminoids
could be readily separated within 7 min with a 15 mM sodium tetraborate buffer
containing 10% methanol (v/v) at pH 10.8, 25 kV and 30 degrees C. The method has
been validated and shows good performance with respect to selectivity,
reproducibility, linearity, limits of detection and recovery. The proposed
method was successfully applied to determine the curcuminoids in urine.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15907631 [PubMed - indexed for MEDLINE]

89: Cancer Lett. 2005 Jun 8;223(2):181-90. Epub 2004 Nov 11.

Chemopreventive and therapeutic effects of curcumin.

Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F, Henry E, Dicato M,
Diederich M.

Laboratoire de Biologie Moleculaire et Cellulaire du Cancer, Hopital Kirchberg,
9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.

Chemoprevention is a promising anti-cancer approach with reduced secondary
effects in comparison to classical chemotherapy. Curcumin, one of the most
studied chemopreventive agents, is a natural compound extracted from Curcuma
longa L. that allows suppression, retardation or inversion of carcinogenesis.
Curcumin is also described as an anti-tumoral, anti-oxidant and
anti-inflammatory agent capable of inducing apoptosis in numerous cellular
systems. In this review, we describe both properties and mode of action of
curcumin on carcinogenesis, gene expression mechanisms and drug metabolism.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 15896452 [PubMed - indexed for MEDLINE]

90: J Cell Physiol. 2005 Dec;205(3):379-86.

Curcumin prevents methylglyoxal-induced oxidative stress and apoptosis in mouse
embryonic stem cells and blastocysts.

Hsuuw YD, Chang CK, Chan WH, Yu JS.

Department of Animal Science, National Pingtung University of Science and
Technology, Taiwan, Republic of China.

Methylglyoxal (MG) is a reactive dicarbonyl compound endogenously produced
mainly from glycolytic intermediates. Elevated MG levels in diabetes patients
are believed to contribute to diabetic complications. MG is cytotoxic through
induction of apoptosis. Curcumin, the yellow pigment of Curcuma longa, is known
to have antioxidant and anti-inflammatory properties. In the present study, we
examined the effect of curcumin on apoptotic biochemical events caused by
incubation of ESC-B5 cells with MG. Curcumin inhibited the MG-induced DNA
fragmentation, caspase-3 activation, cleavage of PARP, mitochondrial cytochrome
c release, and JNK activation. Importantly, curcumin also inhibited the
MG-stimulated increase of reactive oxygen species (ROS) in these cells. In
addition, we demonstrated that curcumin prevented the MG-induced apoptosis of
mouse blastocysts isolated from pregnant mice. Moreover, curcumin significantly
reduced the MG-mediated impairment of blastocyst development from mouse morulas.
The results support the hypothesis that curcumin inhibits MG-induced apoptosis
in mouse ESC-B5 cells and blastocysts by blocking ROS formation and subsequent
apoptotic biochemical events. (c) 2005 Wiley-Liss, Inc.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15887245 [PubMed - indexed for MEDLINE]

91: Indian J Physiol Pharmacol. 2005 Jan;49(1):111-4.

Protective effect of curcumin during selenium induced toxicity on dehydrogenases
in hepatic tissue.

Padmaja S, Raju TN.

Physiology Division, Department of Zoology, University College of Science,
Osmania University, Hyderabad - 500 007.

Selenium administration resulted in a marked decrease in the activity levels of
the liver succinate dehydrogenase, malate dehydrogenase, and lactate
dehydrogenase while pyruvate dehydrogenase increased significantly (P<0.001) in
the wistar rat. The degree of decrease of these enzymes was significantly less
(P<0.001) when rats were treated with curcumin, a natural constituent Curcuma
longa. Curcumin seems to prevent oxidative damage mediated through selenium and
protect the dehydrogenases possibly through its anti-oxidative property.

Publication Types:
Comparative Study

PMID: 15881869 [PubMed - indexed for MEDLINE]

92: J Biol Chem. 2005 Jul 1;280(26):25284-90. Epub 2005 May 6.

Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular
mechanism for its anticancer activity.

Fang J, Lu J, Holmgren A.

Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and
Biophysics, Karolinska Institute, SE-17177 Stockholm, Sweden.

The thioredoxin reductase (TrxR) isoenzymes, TrxR1 in cytosol or nucleus and
TrxR2 in mitochondria, are essential mammalian selenocysteine (Sec)-containing
flavoenzymes with a -Gly-Cys-Sec-Gly active site. TrxRs are the only enzymes
catalyzing the NADPH-dependent reduction of the active site disulfide in
thioredoxins (Trxs), which play essential roles in substrate reductions, defense
against oxidative stress, and redox regulation by thiol redox control. TrxRs
have been found to be overexpressed by a number of human tumors. Curcumin, which
is consumed daily by millions of people, is a polyphenol derived from the plant
Curcuma longa. This phytochemical has well known anticancer and antiangiogenic
properties. In this study we report that rat TrxR1 activity in Trx-dependent
disulfide reduction was inhibited by curcumin. The IC(50) value for the enzyme
was 3.6 microM after incubation at room temperature for 2 h in vitro. The
inhibition occurred with enzyme only in the presence of NADPH and persisted
after removal of curcumin. By using mass spectrometry and blotting analysis, we
proved that this irreversible inhibition by curcumin was caused by alkylation of
both residues in the catalytically active site (Cys(496)/Sec(497)) of the
enzyme. However, the curcumin-modified enzyme showed a strongly induced NADPH
oxidase activity to produce reactive oxygen species. Inhibition of TrxR by
curcumin added to cultured HeLa cells was also observed with an IC(50) of around
15 microM. Modification of TrxR by curcumin provides a possible mechanistic
explanation for its cancer preventive activity, shifting the enzyme from an
antioxidant to a prooxidant.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15879598 [PubMed - indexed for MEDLINE]

93: Int J Low Extrem Wounds. 2003 Mar;2(1):25-39.

Plant medicines of Indian origin for wound healing activity: a review.

Biswas TK, Mukherjee B.

Department of Sharira Kriya, J. B. Roy State Ayurvedic Medical College and
Hospital.

Research on wound healing drugs is a developing area in modern biomedical
sciences. Scientists who are trying to develop newer drugs from natural
resources are looking toward the Ayurveda, the Indian traditional system of
medicine. Several drugs of plant, mineral, and animal origin are described in
the Ayurveda for their wound healing properties under the term Vranaropaka. Most
of these drugs are derived from plant origin. Some of these plants have been
screened scientifically for the evaluation of their wound healing activity in
different pharmacological models and patients, but the potential of most remains
unexplored. In a few cases, active chemical constituents were identified. Some
Ayurvedic medicinal plants, namely, Ficus bengalensis, Cynodon dactylon,
Symplocos racemosa, Rubia cordifolia, Pterocarpus santalinus, Ficus racemosa,
Glycyrrhiza glabra, Berberis aristata, Curcuma longa, Centella asiatica,
Euphorbia nerifolia, and Aloe vera, were found to be effective in experimental
models. This paper presents a limited review of plants used in Ayurvedic
medicine.

PMID: 15866825 [PubMed]

94: Biol Pharm Bull. 2005 May;28(5):937-9.

Hypoglycemic effects of turmeric (Curcuma longa L. rhizomes) on genetically
diabetic KK-Ay mice.

Kuroda M, Mimaki Y, Nishiyama T, Mae T, Kishida H, Tsukagawa M, Takahashi K,
Kawada T, Nakagawa K, Kitahara M.

The turmeric (Curcuma longa L. rhizomes) EtOH extract significantly suppressed
an increase in blood glucose level in type 2 diabetic KK-A(y) mice. In an in
vitro evaluation, the extract stimulated human adipocyte differentiation in a
dose-dependent manner and showed human peroxisome proliferator-activated
receptor (PPAR)-gamma ligand-binding activity in a GAL4-PPAR-gamma chimera
assay. The main constituents of the extract were identified as curcumin,
demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone, which had also
PPAR-gamma ligand-binding activity. These results indicate that turmeric is a
promising ingredient of functional food for the prevention and/or amelioration
of type 2 diabetes and that curcumin, demethoxycurcumin, bisdemethoxycurcumin,
and ar-turmerone mainly contribute to the effects via PPAR-gamma activation.

Publication Types:
Comparative Study
Letter

PMID: 15863912 [PubMed - indexed for MEDLINE]

95: Life Sci. 2005 May 13;76(26):3089-105.

Pharmacological basis for the use of turmeric in gastrointestinal and
respiratory disorders.

Gilani AH, Shah AJ, Ghayur MN, Majeed K.

Department of Biological and Biomedical Sciences, The Aga Khan University
Medical College, Karachi-74800, Sindh, Pakistan. [email protected]

This study was carried out to provide scientific basis for the medicinal use of
turmeric (Curcuma longa) in gastrointestinal and respiratory disorders. The
crude extract of turmeric (Cl.Cr), relaxed the spontaneous and K+ (80
mM)-induced contractions in isolated rabbit jejunum as well as shifted the CaCl2
concentration-response curves. In rabbit tracheal preparation, Cl.Cr inhibited
carbachol and K(+)-induced contractions. In anesthetized rats, Cl.Cr produced
variable responses on blood pressure with a mixture of weak hypertensive and
hypotensive actions. In rabbit aorta, Cl.Cr caused a weak vasoconstrictor and a
vasodilator effect on K+ and phenylephrine-induced contractions. In guinea-pig
atria, Cl.Cr inhibited spontaneous rate and force of contractions at 14-24 times
higher concentrations. Activity directed fractionation revealed that the
vasodilator and vasoconstrictor activities are widely distributed in the plant
with no clear separation into the polar or non-polar fractions. When used for
comparison, both curcumin and verapamil caused similar inhibitory effects in all
smooth muscle preparations with relatively more effect against K(+)-induced
contractions and that both were devoid of any vasoconstrictor effect and
curcumin had no effect on atria. These data suggest that the inhibitory effects
of Cl.Cr are mediated primarily through calcium channel blockade, though
additional mechanism cannot be ruled out and this study forms the basis for the
traditional use of turmeric in hyperactive states of the gut and airways.
Furthermore, curcumin, the main active principle, does not share all effects of
turmeric.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15850601 [PubMed - indexed for MEDLINE]

96: Curr Cancer Drug Targets. 2005 Mar;5(2):117-29.

Induction of apoptosis by curcumin and its implications for cancer therapy.

Karunagaran D, Rashmi R, Kumar TR.

Cancer Biology Laboratory, Rajiv Gandhi Centre for Biotechnology,
Thiruvananthapuram, Kerala 695 014, India. [email protected]

Curcumin (diferuloyl methane), the yellow pigment in turmeric (Curcuma longa),
is a potent chemopreventive agent that inhibits proliferation of cancer cells by
arresting them at various phases of the cell cycle depending upon the cell type.
Curcumin-induced apoptosis mainly involves the mitochondria-mediated pathway in
various cancer cells of different tissues of origin. In some cell types like
thymocytes, curcumin induces apoptosis-like changes whereas in many other normal
and primary cells curcumin is either inactive or inhibits proliferation, but
does not appear to induce apoptosis. These together with reports that curcumin
protects cells against apoptosis induced by other agents, underscore the need
for further understanding of the multiple mechanisms of cell death unleashed by
curcumin. Tumor cells often evade apoptosis by expressing several antiapoptotic
proteins, down-regulation and mutation of proapoptotic genes and alterations in
signaling pathways that give them survival advantage and thereby allow them to
resist therapy-induced apoptosis. Many researchers including ourselves, have
demonstrated the involvement of several pro and antiapoptotic molecules in
curcumin-induced apoptosis, and ways to sensitize chemoresistant cancer cells to
curcumin treatment. This review describes the mechanisms of curcumin-induced
apoptosis currently known, and suggests several potential strategies that
include down-regulation of antiapoptotic proteins by antisense oligonucleotides,
use of proapoptotic peptides and combination therapy, and other novel approaches
against chemoresistant tumors. Several factors including pharmacological safety,
scope for improvement of structure and function of curcumin and its ability to
attack multiple targets are in favor of curcumin being developed as a drug for
prevention and therapy of various cancers.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 15810876 [PubMed - indexed for MEDLINE]

97: Zhongguo Zhong Yao Za Zhi. 2005 Mar;30(6):419-21.

[Effects of seeding and sowing methods on the yields of root tubers of Curcuma
longa]

[Article in Chinese]

Li QM, Jiang RL, Lei JL, Zhang Y, Xia YL, Fang QM, Wang ZW.

Sichuan Institute of Chinese Materia Medica, Chengdu 610041, China.
[email protected]

OBJECTIVE: To provide a scientific basis for standardizing the cultivation
method for Curcuma longa. METHOD: Plant heights and seeding numbers were sampled
periodically, the plot yields were counted a tharvested. RESULT: The effects of
seeding method on yields, plant height and number were significant. The effects
of different sowing ways on the yields were very little. CONCLUSION: The hole
seeding method using mother tuber or blastostyle bearing three to four knots was
shown to be the best may, worthy to be widely applied in production.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't

PMID: 15810443 [PubMed - indexed for MEDLINE]

98: Fitoterapia. 2005 Mar;76(2):254-7.

Biological effects of indigenous medicinal plants Curcuma longa and Alpinia
galanga.

Khattak S, Saeed-ur-Rehman, Ullah Shah H, Ahmad W, Ahmad M.

Department of Chemistry, University of Peshawar, Pakistan.
[email protected]

The ethanolic extracts of Curcuma longa and Alpinia galanga exhibited excellent
(100%) phytotoxic activity against Lemma minor. These extracts were also found
to possess good antifungal activities against Trichophyton longifusus (65% and
60%, respectively), while in the brine shrimp lethality bioassay were found to
be toxic with LD50 of 33 and 109 mincrog/ml, respectively. These extracts were
found quite inert in antibacterial bioassay, while the extract from C. longa,
tested for insecticidal activity, was also found to be devoid of any activity.

PMID: 15810156 [PubMed - indexed for MEDLINE]

99: Se Pu. 2004 Nov;22(6):609-12.

[Determination of curcumin in urine by capillary electrophoresis]

[Article in Chinese]

Yuan K, Weng Q, Zhang H, Xiong J, Yang J, Xu G.

National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics,
The Chinese Academy of Sciences, Dalian 116011, China.

The major component of the plant curcuma longa (a widely cultivated tropical
plant in Asia and Central America) is curcumin. Curcumin has been reported to
have very strong anti-inflammatory, anti-carcinogenic, anti-oxidant,
antiallergic, anti-bacterial, and anti-tumor activities. Little is known about
the absorption, distribution, and metabolism of curcumin in human beings. The
first step in in vivo physiological and pharmacokinetic studies is to develop a
method to measure curcumin in body fluid. A rapid capillary electrophoretic (CE)
method with diode array detection was established for the determination of
curcumin in human urine. It could be rapidly determined within 2.5 min. The
optimized experimental conditions were as follows: 15 mmol/L Na2B4O7 as buffer,
applied voltage 20 kV, temperature 25 degrees C and detection wavelength 262 nm.
The method has been validated and shows good performance with respect to
selectivity, reproducibility and limit of detection. Curcumin had good linearity
in the range of 10 - 300 mg/L, and the recoveries of curcumin added in urine
were more than 96.3% with relative standard deviations (RSDs) less than 2.3%.
The method is sensitive, fast and accurate and can be used to determine curcumin
in urine.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't

PMID: 15807112 [PubMed - indexed for MEDLINE]

100: J Physiol Pharmacol. 2005 Mar;56 Suppl 1:51-69.

Nutraceuticals as anti-angiogenic agents: hopes and reality.

Dulak J.

Department of Cell Biochemistry, Faculty of Biotechnology, Jagiellonian
University, Krakow, Poland. [email protected]

Angiogenesis, the formation of new blood vessels from preexisting vascular
network is a driving force of organ development in ontogeny, is necessary for
ovulation and hair growth, and is prerequisite for proper wound healing. It is
also a critical mechanism of numerous diseases, the most important of which are
cancer and atherosclerosis. Therefore, modulation of angiogenesis is considered
as therapeutic strategies of great importance for human health. Numerous
bioactive plant compounds, often referred to as nutraceuticals are recently
tested for the potential clinical applications. Among the most frequently
studied are resveratrol, a polyphenol present in red-wine and grape-seed,
epigallocatechin-3-gallate (EGCG) from green tea and curcumin from Curcuma
longa. It is also possible that components of other plants, including the
constituents of local food diet may find application for modulation of
angiogenesis, provided that their effectiveness will be confirmed in controlled,
scientifically validated trials.

PMID: 15800385 [PubMed - in process]

101: Biochem Pharmacol. 2005 Apr 15;69(8):1205-13.

Curcumin-induced histone hypoacetylation: the role of reactive oxygen species.

Kang J, Chen J, Shi Y, Jia J, Zhang Y.

School of Life Sciences, Institute of Physics, Lanzou University, Lanzou 730000,
China. [email protected]

Curcumin (Cur), a well-known dietary pigment derived from Curcuma longa, is a
promising anticancer drug, but its in vivo target molecules remain to be
clarified. Here we report that exposure of human hepatoma cells to Cur led to a
significant decrease of histone acetylation. Histone acetyltransferase (HAT) and
histone deacetylase (HDAC) are the enzymes controlling the state of histone
acetylation in vivo. Cur treatment resulted in a comparable inhibition of
histone acetylation in the absence or presence of trichostatin A (the specific
HDAC inhibitor), and showed no effect on the in vitro activity of HDAC. In
contrast, the domain negative of p300 (a most potent HAT protein) could block
the inhibition of Cur on histone acetylation; and the Cur treatment
significantly inhibited the HAT activity both in vivo and in vitro. Thus, it is
HAT, but not HDAC that is involved in Cur-induced histone hypoacetylation. At
the same time, exposure of cells to low or high concentrations of Cur diminished
or enhanced the ROS generation, respectively. And the promotion of ROS was
obviously involved in Cur-induced histone hypoacetylation, since Cur-caused
histone acetylation and HAT activity decrease could be markedly diminished by
the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) or their
combination, but not by their heat-inactivated forms. The data presented here
prove that HAT is one of the in vivo target molecules of Cur; through inhibiting
its activity, Cur induces histone hypoacetylation in vivo, where the ROS
generation plays an important role. Considering the critical roles of histone
acetylation in eukaryotic gene transcription and the involvement of histone
hypoacetylation in the lose of cell viability caused by high concentrations of
Cur, these results open a new door for us to further understand the molecular
mechanism involved in the in vivo function of Cur.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15794941 [PubMed - indexed for MEDLINE]

102: Bioorg Med Chem Lett. 2005 Apr 1;15(7):1793-7.

Design, synthesis, biological evaluation and molecular docking of curcumin
analogues as antioxidant, cyclooxygenase inhibitory and anti-inflammatory
agents.

Selvam C, Jachak SM, Thilagavathi R, Chakraborti AK.

Department of Natural Products, National Institute of Pharmaceutical Education
and Research (NIPER), Sector 67, SAS Nagar, Punjab 160 062, India.

Curcuminoids were isolated from Curcuma longa and their pyrazole and isoxazole
analogues were synthesized and evaluated for antioxidant, COX-1/COX-2 inhibitory
and anti-inflammatory activities. The designed analogues significantly enhance
COX-2/COX-1 selectivity and possess significant anti-inflammatory activity in
carrageenan induced rat paw edema assay. Pyrazole, isoxazole analogues of
curcumin (4 and 7) exhibited higher antioxidant activity than trolox. Molecular
docking study revealed the binding orientations of curcumin analogues in the
active sites of COX and thereby helps to design novel potent inhibitors.

Publication Types:
Evaluation Studies

PMID: 15780608 [PubMed - indexed for MEDLINE]

103: J Agric Food Chem. 2005 Feb 23;53(4):959-63.

Curcuminoids and sesquiterpenoids in turmeric (Curcuma longa L.) suppress an
increase in blood glucose level in type 2 diabetic KK-Ay mice.

Nishiyama T, Mae T, Kishida H, Tsukagawa M, Mimaki Y, Kuroda M, Sashida Y,
Takahashi K, Kawada T, Nakagawa K, Kitahara M.

Functional Foods Development Division, and Life Science Research Laboratories,
Life Science RD Center, Kaneka Corporation, Takasago, Hyogo 676-8688, Japan.

Turmeric, the rhizome of Curcuma longa L., has a wide range of effects on human
health. The chemistry includes curcuminoids and sesquiterpenoids as components,
which are known to have antioxidative, anticarcinogenic, and antiinflammatory
activities. In this study, we investigated the effects of three turmeric
extracts on blood glucose levels in type 2 diabetic KK-A(y) mice (6 weeks old, n
= 5/group). These turmeric extracts were obtained by ethanol extraction (E-ext)
to yield both curcuminoids and sesquiterpenoids, hexane extraction (H-ext) to
yield sesquiterpenoids, and ethanol extraction from hexane-extraction residue
(HE-ext) to yield curcuminoids. The control group was fed a basal diet, while
the other groups were fed a diet containing 0.1 or 0.5 g of H-ext or HE-ext/100
g of diet or 0.2 or 1.0 g of E-ext/100 g of diet for 4 weeks. Although blood
glucose levels in the control group significantly increased (P < 0.01) after 4
weeks, feeding of 0.2 or 1.0 g of E-ext, 0.5 g of H-ext, and 0.5 g of HE-ext/100
g of diet suppressed the significant increase in blood glucose levels.
Furthermore, E-ext stimulated human adipocyte differentiation, and these
turmeric extracts had human peroxisome proliferator-activated receptor-gamma
(PPAR-gamma) ligand-binding activity in a GAL4-PPAR-gamma chimera assay. Also,
curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone had
PPAR-gamma ligand-binding activity. These results indicate that both
curcuminoids and sesquiterpenoids in turmeric exhibit hypoglycemic effects via
PPAR-gamma activation as one of the mechanisms, and suggest that E-ext including
curcuminoids and sesquiterpenoids has the additive or synergistic effects of
both components.

PMID: 15713005 [PubMed - indexed for MEDLINE]

104: J Altern Complement Med. 2004 Dec;10(6):1015-8.

Turmeric extract may improve irritable bowel syndrome symptomology in otherwise
healthy adults: a pilot study.

Bundy R, Walker AF, Middleton RW, Booth J.

Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, The
University of Reading, Reading, UK. [email protected]

OBJECTIVES: To assess the effects of turmeric (Curcuma longa) extract on
irritable bowel syndrome (IBS) symptomology in otherwise healthy adults. DESIGN:
Partially blinded, randomized, two-dose, pilot study. SUBJECTS: Five hundred
(500) volunteers were screened for IBS using the Rome II criteria. Two hundred
and seven (207) suitable volunteers were randomized. INTERVENTIONS: One or two
tablets of a standardized turmeric extract taken daily for 8 weeks. OUTCOMES
MEASURES: IBS prevalence, symptom-related quality of life (IBSQOL) and
self-reported effectiveness. RESULTS: IBS prevalence decreased significantly in
both groups between screening and baseline (41% and 57%), with a further
significant drop of 53% and 60% between baseline and after treatment, in the
one- and two-tablet groups respectively (p < 0.001). A post-study analysis
revealed abdominal pain/discomfort score reduced significantly by 22% and 25% in
the one- and two-tablet group respectively, the difference tending toward
significance (p = 0.071). There were significant improvements in all bar one of
the IBSQOL scales of between 5% and 36% in both groups, approximately two thirds
of all subjects reported an improvement in symptoms after treatment, and there
was a favorable shift in self-reported bowel pattern. There were no significant
differences between groups. CONCLUSIONS: Turmeric may help reduce IBS
symptomology. Placebo controlled trials are now warranted to confirm these
findings.

Publication Types:
Clinical Trial
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

PMID: 15673996 [PubMed - indexed for MEDLINE]

105: Basic Clin Pharmacol Toxicol. 2005 Jan;96(1):80-7.

Screening of antioxidants from medicinal plants for cardioprotective effect
against doxorubicin toxicity.

Wattanapitayakul SK, Chularojmontri L, Herunsalee A, Charuchongkolwongse S,
Niumsakul S, Bauer JA.

Department of Pharmacology, Faculty of Medicine, Srinakharinwirot University,
Bangkok 10110, Thailand. [email protected]

Doxorubicin is an important and effective anticancer drug widely used for the
treatment of various types of cancer but its clinical use is limited by
dose-dependent cardiotoxicity. Elevated tissue levels of cellular superoxide
anion/oxidative stress are a mechanism by which doxorubicin-induced
cardiotoxicity. Selected medicinal plant extracts were tested for their
antioxidant capacity and cardioprotective effect against doxorubicin-induced
cardiotoxicity. The cardiac myoblasts H9c2 were incubated with the antioxidants
ascorbic acid, trolox, N-acetylcysteine or selected medicinal plant extracts
including; 1) ethanolic extracts from Curcuma longa L-EtOH Phyllanthus emblica
L-EtOH, and Piper rostratum Roxb-EtOH; and 2) water extracts from Curcuma longa
L-H2O and Morus alba L-H2O. The cardioprotective effects of these extracts were
evaluated by crystal violet cytotoxicity assay. IC50s of doxorubicin were
compared in the presence or absence of ascorbic acids, trolox, N-acetylcysteine
or plant extracts. Morus alba L-H2O showed the highest antioxidant properties
evaluated by ferric reducing/antioxidant power assay. Ascorbic acid and
N-acetylcysteine had modest effects on the protection of doxorubicin-induced
cytotoxicity while trolox showed insignificant protective effect. All plant
extracts protected cardiac toxicity at different degrees except that Curcuma
longa L-EtOH had no protective effect. Phyllanthus emblica-EtOH (100 microg/ml)
showed the highest cardioprotective effect (approximately 12-fold doxorubicin
IC50 increase). The data demonstrate that antioxidants from natural sources may
be useful in the protection of cardiotoxicity in patients who receive
doxorubicin.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15667600 [PubMed - indexed for MEDLINE]

106: Zhongguo Zhong Yao Za Zhi. 2004 Sep;29(9):857-60.

[Study on the SFE condition for curcumin in Curcuma longa]

[Article in Chinese]

Su SL, Wu QN, Ouyang Z, Wu DK, Chen J.

Department of Pharmaceutical Engineering of Jiangsu University, Zhenjian 212013
China. [email protected]

OBJECTIVE: To optimize the conditions of supercritical fluid extraction (SFE)
for curcumin in Curcuma longa. METHOD: Optimum extraction conditions were
studied by orthogonal tests. The extracts were analyzed by HPLC. RESULT: The
optimal extraction conditions were pressure 25 MPa, temperature 55 degrees C,
static time 4 h, dynamic time 5 h, flow rate of CO2 3.5 L x min(-1), co-solvent
ethanol 30% (mL x g(-1)). CONCLUSION: It is feasible to extract curcumin by SFE.

Publication Types:
English Abstract

PMID: 15575202 [PubMed - indexed for MEDLINE]

107: Phytother Res. 2004 Oct;18(10):798-804.

Antioxidant availability of turmeric in relation to its medicinal and culinary
uses.

Tilak JC, Banerjee M, Mohan H, Devasagayam TP.

Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre,
Mumbai 400 085, India.

Turmeric (Curcuma longa) has been used in Indian cooking, and in herbal
remedies. Its possible mechanism of action was examined in terms of antioxidant
availability during actual cooking conditions and in therapeutic applications
using standardized extracts. The assays involve different levels of antioxidant
action such as oxygen radical absorbance capacity (ORAC), radical scavenging
abilities using 1,1-diphenyl-2-picryl hydrazyl (DPPH),
2,2'-azobis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS), ferric reducing
antioxidant power (FRAP) and protection of membranes examined by inhibition of
lipid peroxidation besides the content of phenols and total flavonoids. The
aqueous and ethanol extracts of two major preparations of turmeric,
corresponding to its use in cooking and medicine, showed significant antioxidant
abilities. In conclusion, the studies reveal that the ability of turmeric to
scavenge radicals, reduce iron complex and inhibit peroxidation may explain the
possible mechanisms by which turmeric exhibits its beneficial effects in
relation to its use in cooking and medicine. Copyright 2004 John Wiley & Sons,
Ltd.

PMID: 15551376 [PubMed - indexed for MEDLINE]

108: J Pharm Pharmacol. 2004 Nov;56(11):1435-42.

Antihyperglycaemic and antioxidant effect of hyponidd, an ayurvedic herbomineral
formulation in streptozotocin-induced diabetic rats.

Babu PS, Stanely Mainzen Prince P.

Department of Biochemistry, Annamalai University, Annamalai Nagar-608 002, Tamil
Nadu, India.

Hyponidd is a herbomineral formulation composed of the extracts of ten medicinal
plants ( Momordica charantia, Melia azadirachta, Pterocarpus marsupium,
Tinospora cordifolia , Gymnema sylvestre, Enicostemma littorale, Emblica
officinalis, Eugenia jambolana, Cassia auriculata and Curcuma longa). We have
investigated hyponidd for its possible antihyperglycaemic and antioxidant effect
in diabetic rats. Rats were rendered diabetic by streptozotocin (STZ) (45 mg
kg(-1) body weight). Oral administration of hyponidd (100 mg kg(-1) and 200 mg
kg(-1)) for 45 days resulted in significant lowered levels of blood glucose and
significant increased levels of hepatic glycogen and total haemoglobin. An oral
glucose tolerance test was also performed in experimental diabetic rats in which
there was a significant improvement in blood glucose tolerance in the rats
treated with hyponidd. Hyponidd administration also decreased levels of
glycosylated haemoglobin, plasma thiobarbituric acid reactive substances,
hydroperoxides, ceruloplasmin and alpha-tocopherol in diabetic rats. Plasma
reduced glutathione and vitamin C were significantly elevated by oral
administration of hyponidd. The effect of hyponidd at a dose of 200 mg kg(-1)
was more effective than glibenclamide (600 microg kg(-1)) in restoring the
values to near normal. The results showed that hyponidd exhibits
antihyperglycaemic and antioxidant activity in STZ-induced diabetic rats.

PMID: 15525451 [PubMed - indexed for MEDLINE]

109: Mol Cancer Ther. 2004 Sep;3(9):1101-8.

Effect of curcumin on normal and tumor cells: role of glutathione and bcl-2.

Syng-Ai C, Kumari AL, Khar A.

Center for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.

Curcumin, a well-known dietary pigment derived from Curcuma longa, inhibited
growth of several types of malignant cells both in vivo and in vitro. However,
its mechanism of action still remains unclear. In this study, we have focused
primarily on the cytotoxic effects of curcumin on three human tumor cell lines
and rat primary hepatocytes. Curcumin induced apoptosis in MCF-7, MDAMB, and
HepG2 cells in a dose-dependent and time-dependent manner. Apoptosis was
mediated through the generation of reactive oxygen species. Attempts were made
to establish the role played by endogenous glutathione on the apoptotic activity
of curcumin. Depletion of glutathione by buthionine sulfoximine resulted in the
increased generation of reactive oxygen species, thereby further sensitizing the
cells to curcumin. Interestingly, curcumin had no effect on normal rat
hepatocytes, which showed no superoxide generation and therefore no cell death.
These observations suggest that curcumin, a molecule with varied actions, could
be developed into an effective chemopreventive and chemotherapeutic agent.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 15367704 [PubMed - indexed for MEDLINE]

110: Life Sci. 2004 Sep 24;75(19):2363-75.

A water extract of Curcuma longa L. (Zingiberaceae) rescues PC12 cell death
caused by pyrogallol or hypoxia/reoxygenation and attenuates hydrogen peroxide
induced injury in PC12 cells.

Koo BS, Lee WC, Chung KH, Ko JH, Kim CH.

Department of Biochemistry, Molecular Biology and Neurobiology, College of
Oriental Medicine, DongGuk University, Kyungju City, Kyungbuk 780-714, Republic
of Korea.

A number of studies indicate that free radicals are involved in the
neurodegeneration in Alzheimer's disease (AD). The role of superoxide anion
(O2*-) in neuronal cell injury induced by reactive oxygen species (ROS) was
examined in PC12 cells using pyrogallol (1,2,3-benzenetrior), a donor to release
O2*-. Pyrogallol induced PC12 cell death at concentrations, which evidently
increased intracellular O2*-, as assessed by O2*- sensitive fluorescent
precursor hydroethidine (HEt). A water extract of Curcuma longa L.
(Zingiberaceae) (CLE), having O2*- scavenging activity rescued PC12 cells from
pyrogallol-induced cell death. Hypoxia/reoxygenation injury of PC12 cells was
also blocked by CLE. The present study was also conducted to examine the effect
of CLE on H2O2 -induced toxicity in rat pheochromocytoma line PC12 by measuring
cell lesion, level of lipid peroxidation and antioxidant enzyme activities.
Following a 30 min exposure of the cells to H2O2 (150 microM), a marked decrease
in cell survival, activities of glutathione peroxidase and catalase as well as
increased production of malondialdehyde (MDA) were found. Pretreatment of the
cells with CLE (0.5-10 microg/ml) prior to H2O2 exposure significantly elevated
the cell survival, antioxidant enzyme activities and decreased the level of MDA.
The above-mentioned neuroprotective effects are also observed with tacrine (THA,
1 microM), suggesting that the neuroprotective effects of cholinesterase
inhibitor might partly contribute to the clinical efficacy in AD treatment.
Further understanding of the underlying mechanism of the protective effects of
these radical scavengers reducing intracellular O2*- on neuronal cell death may
lead to development of new therapeutic treatments for hypoxic/ischemic brain
injury.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15350833 [PubMed - indexed for MEDLINE]

111: Life Sci. 2004 Aug 20;75(14):1701-11.

Protective effects of Curcuma longa on ischemia-reperfusion induced myocardial
injuries and their mechanisms.

Mohanty I, Singh Arya D, Dinda A, Joshi S, Talwar KK, Gupta SK.

Department of Pharmacology, All India Institute of Medical Sciences, Ansari
Nagar, New Delhi-110029.

The present study was undertaken to evaluate the cardioprotective potential of
Curcuma longa (Turmeric) in the ischemia-reperfusion (I/R) model of myocardial
infarction (MI). Wistar rats were divided into three groups and received saline
orally (sham, control I/R group) and Curcuma longa 100 mg/kg (CL-100 treated
group) respectively for one month. On the 31st day, rats of the control I/R and
Cl treated groups were subjected to 45 min of occlusion of the LAD coronary
artery and were thereafter reperfused for 1 h. I/R resulted in significant
cardiac necrosis, depression in left ventricular function, decline in
antioxidant status and elevation in lipid perodixation in the control I/R group
as compared to sham control. Myocardial infarction produced after I/R was
significantly reduced in the Cl treated group. Cl treatment resulted in
restoration of the myocardial antioxidant status and altered hemodynamic
parameters as compared to control I/R. Furthermore, I/R-induced lipid
peroxidation was significantly inhibited by Cl treatment. The beneficial
cardioprotective effects also translated into the functional recovery of the
heart. Cardioprotective effect of Cl likely results from the suppression of
oxidative stress and correlates with the improved ventricular function.
Histopathological examination further confirmed the protective effects of Cl on
the heart.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 15268970 [PubMed - indexed for MEDLINE]

112: Bioinformatics. 2004 Aug 4;20 Suppl 1:I290-I296.

Mining MEDLINE for implicit links between dietary substances and diseases.

Srinivasan P, Libbus B.

School of Library and Information Science, University of Iowa, Iowa City, IA
52242, USA.

MOTIVATION: Text mining systems aim at knowledge discovery from text
collections. This work presents our text mining algorithm and demonstrates its
use to uncover information that could form the basis of new hypotheses. In
particular, we use it to discover novel uses for Curcuma longa, a dietary
substance, which is highly regarded for its therapeutic properties in Asia.
RESULTS: Several disease were identified that offer novel research contexts for
curcumin. We analyze select suggestions, such as retinal diseases, Crohn's
disease and disorders related to the spinal cord. Our analysis suggests that
there is strong evidence in favor of a beneficial role for curcumin in these
diseases. The evidence is based on curcumin's influence on several genes, such
as COX-2, TNF-alpha, JNK, p38 MAPK and TGF-beta. This research suggests that our
discovery algorithm may be used to suggest novel uses for dietary and
pharmacological substances. More generally, our text mining algorithm may be
used to uncover information that potentially sheds new light on a given topic of
interest. AVAILABILITY: Contact authors.

PMID: 15262811 [PubMed - in process]

113: J Assoc Physicians India. 2003 Nov;51:1055-60.

Early human safety study of turmeric oil (Curcuma longa oil) administered orally
in healthy volunteers.

Joshi J, Ghaisas S, Vaidya A, Vaidya R, Kamat DV, Bhagwat AN, Bhide S.

Bhavan's Swami Prakashananda Ayurveda Research Centre, 13th NS Road, Juhu,
Mumbai 400 049.

OBJECTIVE: Turmeric extract and turmeric oil have shown chemoprotective effect
against chemically-induced malignancies in experimental animals. They can
reverse precancerous changes in oral submucous fibrosis in humans. The use of
turmeric or Curcuma longa Linn as a spice and household remedy has been known to
be safe for centuries. In view of the long term administration required for
cancer prevention a Phase I clinical trial of turmeric oil (TO) was designed to
study the safety and tolerance of TO in volunteers for a period of 3 months.
MATERIAL AND METHODS: Nine healthy volunteers between 20 and 33 years of age
were tested for haemoglobin, blood counts, liver and kidney functions, bleeding
and clotting time and serum electrolytes initially and at 1 and 3 months of
treatment. They were administered 0.6 ml of TO three times a day for 1 month and
1 ml in 3 divided doses for 2 months. The acute tolerability study on Day 1 was
conducted in a Clinical Pharmacology daycare Unit. Blood pressure and pulse were
recorded frequently on Day 1 and at 24, 48, 72 and 96 hours and fortnightly till
12 weeks. Volunteers were daily supervised for TO intake as well as for any side
effects throughout the study period. RESULTS: Nine volunteers were enrolled for
the study. One discontinued on 3rd day for allergic skin rashes which, on
discontinuation of TO, gradually disappeared by two weeks. Another discontinued
on 7th day for intercurrent fever requiring antibiotic treatment. Seven
volunteers completed the study. There was no effect of TO, in two doses, on
pulse and blood pressure and no side effects in acute tolerability study on Day
1. There was no effect of TO intake on weight, blood pressure, symptoms and
signs upto 12 weeks. There was no clinical, haematological, renal or
hepatic-toxicity of TO at 1 month and 3 months. Serum lipids did not show
significant change except in one volunteer (reversible). CONCLUSIONS: In view of
the potential for reversing oral submucous fibrosis, a precancerous condition
for oral cancer, TO, can be recommended directly for a Phase II trial in
patients.

Publication Types:
Clinical Trial
Clinical Trial, Phase I

PMID: 15260388 [PubMed - indexed for MEDLINE]

114: Indian J Exp Biol. 2004 Jun;42(6):601-3.

Antioxidant effect of curcumin in selenium induced cataract of Wistar rats.

Padmaja S, Raju TN.

Physiology Division, Department of Zoology, University College of Science,
Osmania University, Hyderabad 500 007, India.

Wistar rat pups treated with curcumin, a natural constituent of Curcuma longa
before being administered with selenium showed no opacities in the lens. The
lipid peroxidation, xanthine oxidase enzyme levels in the lenses of curcumin and
selenium co-treated animals were significantly less when compared to selenium
treated animals. The superoxidase dismutase and catalase enzyme activities of
curcumin and selenium co-treated animal lenses showed an enhancement. Curcumin
co-treatment seems to prevent oxidative damage and found to delay the
development of cataract.

PMID: 15260112 [PubMed - indexed for MEDLINE]

115: Int J Mol Med. 2004 Aug;14(2):253-6.

Induction of apoptosis by ar-turmerone on various cell lines.

Ji M, Choi J, Lee J, Lee Y.

School of Life Science, Shandong University, Jinan 250100, China.

This study investigated the cytotoxic effect of ar-turmerone isolated from
turmeric (Curcuma longa L) on the K562, L1210, U937 and RBL-2H3 cell lines by
the MTT assay. Ar-turmerone exhibited potent cytotoxicity on these cancer cell
lines. The IC50 values of ar-turmerone on these cell lines were 20-50 microg/ml.
They showed an increased inhibition ratio on cell viability according to the
drug concentration < or = 80 microg/ml in the cell lines tested. The DNA
fragmentation that is a characteristic of apoptosis due to ar-turmerone occurred
in a concentration- and time-dependent manner in the K562, L1210, U937 and
RBL-2H3 cancer cell lines. These results suggest that ar-turmerone can induce
the apoptotic activity in the K562, L1210, U937 and RBL-2H3 cells.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15254774 [PubMed - indexed for MEDLINE]

116: Int J Cancer. 2004 Sep 1;111(3):381-7.

In vitro and in vivo anti-tumoral effect of curcumin against melanoma cells.

Odot J, Albert P, Carlier A, Tarpin M, Devy J, Madoulet C.

Laboratoire de Biologie Cellulaire et Moleculaire, EA 3306 U.F.R Sciences,
Reims, France.

Curcumin, the active ingredient from the spice turmeric (Curcuma longa Linn), is
known to be an anti-oxidant and an anti-inflammatory agent. It has been
demonstrated recently to possess anti-angiogenic effects and pro-apoptotic
activities against Ehrlich ascites tumor cells. In the current study, curcumin
was found to be cytotoxic in vitro for B16-R melanoma cells resistant to
doxorubicin either cultivated as monolayers or grown in three-dimensional (3-D)
cultures (spheroids). We have demonstrated that the cytotoxic effect observed in
the 2 culture types can be related to the induction of programmed cell death. In
our in vivo studies, we examined the effectiveness of a prophylactic immune
preparation of soluble proteins from B16-R cells, or a treatment with curcumin
as soon as tumoral appearance, alone or in combination, on the murine melanoma
B16-R. The combination treatment resulted in substantial inhibition of growth of
B16-R melanoma, whereas each treatment by itself showed little effect. Moreover,
animals receiving the combination therapy exhibited an enhancement of their
humoral anti-soluble B16-R protein immune response and a significant increase in
their median survival time (> 82.8% vs. 48.6% and 45.7% respectively for the
immunized group and the curcumin-treated group). Our study shows that curcumin
may provide a valuable tool for the development of a therapeutic combination
against the melanoma. Copyright 2004 Wiley-Liss, Inc.

PMID: 15221965 [PubMed - indexed for MEDLINE]

117: Nat Prod Res. 2004 Aug;18(4):295-9.

Inhibitory activity of diarylheptanoids on farnesyl protein transferase.

Kang HM, Son KH, Yang DC, Han DC, Kim JH, Baek NI, Kwon BM.

Korea Research Institute of Bioscience and Biotechnology, 52 Uendong, Yusung,
Taejon 305-600, Republic of Korea.

Diarylheptanoids [curcumin (1), demethoxycurcumin (2), bisdemethoxycurcumin (3),
bisdimethoxymethylcurcumin (4), and 1,2-dihydrobis(de-O-methyl)curcumin (5)]
were isolated from the methanolic extract of Curcuma longa L. and a new cyclic
diarylheptanoid (6) and a known Compound 7 were isolated from fruits of Alnus
japonica Steud. Diarylheptanoids (1-3) inhibited farnesyl protein transferase
(FPTase) with an IC50 of 29-50 microM. The other compounds very mildly inhibited
FPTase, therefore, the inhibitory activity on FPTase very much depends on the
structure of diarylheptanoids.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15214479 [PubMed - indexed for MEDLINE]

118: Carcinogenesis. 2004 Oct;25(10):1867-77. Epub 2004 Jun 17.

Ectopic expression of Bcl-XL or Ku70 protects human colon cancer cells (SW480)
against curcumin-induced apoptosis while their down-regulation potentiates it.

Rashmi R, Kumar S, Karunagaran D.

Division of Cancer Biology, Rajiv Gandhi Center for Biotechnology,
Thiruvananthapuram, Kerala 695014, India.

Curcumin, the yellow pigment derived from Curcuma longa, is known to induce
apoptosis of several cancer cells. However, many cancer cells protect themselves
by over-expressing antiapoptotic proteins such as Bcl-XL or Ku70. To study their
role in curcumin-induced apoptosis, human colon cancer cells (SW480) were made
to over-express or under-express Bcl-XL (by stable transfection) and Ku70 (by
transient transfection) using plasmid constructs that express their genes in
sense or antisense orientation, respectively. Stable cells that express Bax
[Bax-GFP (green fluorescent protein)], a proapoptotic member of the Bcl-2
family, were also established. Curcumin-induced cell death and nuclear
condensation was more in AsBcl-XL and AsKu70 cells that under-express Bcl-XL and
Ku70, respectively, compared with the vector-transfected cells. Bcl-XL and Ku70
protected the cells by inhibiting the release of cytochrome c, Smac (second
mitochondria derived activator of caspase) and apoptosis inducing factor (AIF),
and the activation of caspases 9, 8 and 3 triggered by curcumin. AsBcl-XL and
AsKu70 cells were more sensitive to curcumin through enhanced activation of
caspases 9 and 3 and release of cytochrome c, Smac and AIF. Curcumin-induced
activation of caspase 8 was blocked by Ku70 but not by Bcl-XL. However, caspase
8 activation by curcumin was accelerated in both AsBcl-XL and AsKu70 cells
suggesting a possible feedback activation of caspase 8 by caspase 3. Bax-GFP
cells were highly sensitized when Ku70 was down-regulated supporting the
reported role of Ku70 in the retention of Bax within the cytosol. The study
reveals the potential of antisense inhibition of antiapoptotic proteins as an
effective strategy to tackle chemoresistant cancers with curcumin.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15205359 [PubMed - indexed for MEDLINE]

119: Phytochem Anal. 2004 May-Jun;15(3):152-8.

Quantitative determination of curcuminoids in Curcuma rhizomes and rapid
differentiation of Curcuma domestica Val. and Curcuma xanthorrhiza Roxb. by
capillary electrophoresis.

Lechtenberg M, Quandt B, Nahrstedt A.

Institute of Pharmaceutical Biology and Phytochemistry, Hittorfstrasse 56,
D-48149 Munster, Germany.

The three major curcuminoids, curcumin, demethoxycurcumin and
bis-demethoxycurcumin, from Curcuma domestica Val. (Curcuma longa L.) and
Curcuma xanthorrhiza Roxb. (Zingiberaceae) were fully separated and quantified
in less than 5 min using a capillary zone electrophoresis method with standard
fused-silica capillaries and photodiode array detection. An electrolyte solution
of 20 mM phosphate, 50 mM sodium hydroxide and 14 mM beta-cyclodextrin was found
to be appropriate. Quantification was performed with
3,4-dimethoxy-trans-cinnamic acid as internal standard, and the limit of
detection was 0.01 mg/mL. Extraction, stabilisation during sample storage and
quantification procedures were optimised and carried out with drugs and
commercial curry powder from different provenances. The results were compared
with the photometric method of the monograph Curcumae xanthorrhizae rhizoma of
the European Pharmacopoeia.

Publication Types:
Comparative Study

PMID: 15202598 [PubMed - indexed for MEDLINE]

120: Kidney Int. 2004 Jul;66(1):112-20.

Curcumin blocks multiple sites of the TGF-beta signaling cascade in renal cells.

Gaedeke J, Noble NA, Border WA.

Fibrosis Research Laboratory, Division of Nephrology, University of Utah, Salt
Lake City, Utah, USA.

BACKGROUND: Over-expression of transforming growth factor-beta (TGF-beta)
contributes greatly to fibrotic kidney disease. The activator protein-1 (AP-1)
inhibitor curcumin, a polyphenolic compound derived from Curcuma longa, has been
shown to reduce collagen accumulation in experimental pulmonary fibrosis. Here,
we investigate curcumin's ability to modulate TGF-beta's profibrotic actions in
vitro. METHODS: NRK49F rat renal fibroblasts were stimulated with TGF-beta (5
ng/mL), and the effects of curcumin on TGF-beta-regulated genes, TGF-beta
receptors, and phosphorylated SMAD isoforms were analyzed by Northern blotting,
enzyme-linked immunosorbent assay (ELISA), and Western blotting. The effects of
c-jun depletion on TGF-beta-regulated gene and protein expression were analyzed
with RNAi. RESULTS: When applied 30 minutes before TGF-beta, curcumin dose
dependently and dramatically reduced TGF-beta-induced increases in plasminogen
activator inhibitor-1 (PAI-1), TGF-beta1, fibronectin (FN) and collagen I (Col
I) mRNA, and in PAI-1 and fibronectin protein. Prolonged curcumin treatment (>6
h) significantly reduced TGF-beta receptor type II levels and SMAD2/3
phosphorylation in response to added TGF-beta. Depletion of cellular c-jun
levels with a RNAi method mimicked the effects of curcumin on expression of
TGF-beta1, FN, and Col I, but not PAI-1. CONCLUSION: Curcumin blocks TGF-beta's
profibrotic actions on renal fibroblasts through down-regulation of TbetaRII,
and through partial inhibition of c-jun activity. These in vitro data suggest
that curcumin might be an effective antifibrotic drug in the treatment of
chronic kidney disease.

PMID: 15200418 [PubMed - indexed for MEDLINE]

121: J Exp Clin Cancer Res. 2004 Mar;23(1):61-8.

Antimutagenicity of herbal detoxification formula Smoke Shield against
environmental mutagens.

Kuttan R, Kuttan G, Joseph S, Ajith TA, Mohan M, Srimal RC.

Amala Cancer Research Centre, Amala Nagar, Kerala, India.

Smoke Shield is a formulation designed to reduce smoke related mutagenicity and
toxicity in the population. Smoke Shield contains a dual extract of turmeric
(Curcuma longa) obtained by supercritical CO2 gas extraction and
post-supercritical hydroethanolic extraction together with extracts of green tea
and other spices, whose presence synergistically increases the activity of
turmeric. In the present study we have shown its antimutagenic activity to
various environmental mutagens in vitro and in vivo. Smoke Shield was found to
produce significant inhibition of mutagenicity to Salmonella typhimurium induced
by sodium azide and 4-nitro-0-phenylenediamine (NPD) at a concentration of 2
mg/plate while inhibition to N-methyl-N-nitro N'nitrosoguanidine was less
significant. Inhibition was also found to depend upon the strain which was used.
Smoke Shield was found to be more effective against mutagens needing metabolic
activation such as 2-Acetamidofluorene (2-AAF) and benzo[a]pyrene. Smoke Shield
was also found to significantly inhibit the mutagenicity induced by tobacco
extract to Salmonella typhimurium TA102. Smoke Shield was also found to inhibit
the urinary mutagenicity of rats treated with the benzo[a]pyrene and tobacco
extract. Moreover, Smoke Shield administration was found to inhibit the urinary
mutagenicity in smokers. These results indicate that Smoke Shield could inhibit
mutagenic response in vitro and in vivo produced by several kinds of mutagens
present in our atmosphere.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15149152 [PubMed - indexed for MEDLINE]

122: Cancer Lett. 2004 May 28;208(2):163-70.

Induction of apoptosis in human lung cancer cells by curcumin.

Radhakrishna Pillai G, Srivastava AS, Hassanein TI, Chauhan DP, Carrier E.

Department of Medicine, Pediatrics and Family and Preventive Medicine, School of
Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA
92093-0062, USA.

Curcumin, a phenolic compound from the rhizome of the plant Curcuma longa has
anti-inflammatory, antioxidant and anti-cancer activities. Although the precise
mode of action of this compound is not yet elucidated, studies have shown that
chemo-preventive action of curcumin might be due to its ability to induce
apoptosis and to arrest cell cycle. This study investigated the cellular and
molecular changes induced by curcumin leading to the induction of apoptosis in
human lung cancer cell lines-A549 and H1299. A549 is p53 proficient and H1299 is
p53 null mutant. The lung cancer cells were treated with curcumin (0-160 microM)
for 12-72 h. Curcumin inhibited the growth of both the cell lines in a
concentration dependent manner. Growth inhibition of H1299 cell lines was both
time and concentration dependent. Curcumin induced apoptosis in both the lung
cancer cell lines. A decrease in expression of p53, bcl-2, and bcl-X(L) was
observed after 12 h exposure of 40 microM curcumin. Bak and Caspase genes
remained unchanged up to 60 microM curcumin but showed decrease in expression
levels at 80-160 microM. The data also suggest a p53 independent induction of
apoptosis in lung cancer cells.

PMID: 15142674 [PubMed - indexed for MEDLINE]

123: Crit Rev Food Sci Nutr. 2004;44(2):97-111.

Biological properties of curcumin-cellular and molecular mechanisms of action.

Joe B, Vijaykumar M, Lokesh BR.

Department of Physiology and Molecular Medicine, Medical College of Ohio, Block
Health Science Building, 3035 Arlington Avenue, Toledo, OH 43614-5804, USA.
[email protected]

Curcuminoids, a group of phenolic compounds isolated from the roots of Curcuma
longa (Zingiberaceae), exhibit a variety of beneficial effects on health and on
events that help in preventing certain diseases. A vast majority of these
studies were carried out with curcumin (diferuloyl methane), which is a major
curcuminoid. The most detailed studies using curcumin include anti-inflammatory,
antioxidant, anticarcinogenic, antiviral, and antiinfectious activities. In
addition, the wound healing and detoxifying properties of curcumin have also
received considerable attention. As a result of extensive research on the
therapeutic properties of curcumin, some understanding on the cellular,
molecular, and biochemical mechanism of action of curcumin is emerging. These
findings are summarized in this review.

Publication Types:
Review

PMID: 15116757 [PubMed - indexed for MEDLINE]

124: J Cell Biochem. 2004 May 1;92(1):200-12.

Anti-apoptotic effects of curcumin on photosensitized human epidermal carcinoma
A431 cells.

Chan WH, Wu HJ.

Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan
Christian University, Chung Li, Taiwan, Republic of China. [email protected]

Photodynamic treatment (PDT) can elicit a diverse range of cellular responses,
including apoptotic cell death. Previously, we showed that PDT stimulates
caspase-3 activation and subsequent cleavage and activation of p21-activated
kinase 2 (PAK2) in human epidermal carcinoma A431 cells. Curcumin, the yellow
pigment of Curcuma longa, is known to have anti-oxidant and anti-inflammatory
properties. In the present study, using Rose Bengal (RB) as the photosensitizer,
we investigated the effect of curcumin on PDT-induced apoptotic events in human
epidermal carcinoma A431 cells. We report that curcumin prevented PDT-induced
JNK activation, mitochondrial release of cytochrome c, caspase-3 activation, and
cleavage of PAK2. Using the cell permeable dye DCF-DA as an indicator of
reactive oxygen species (ROS) generation, we found that both curcumin and ROS
scavengers (i.e., l-histidine, a-tocopherol, mannitol) abolished PDT-stimulated
intracellular oxidative stress. Moreover, all these PDT-induced apoptotic
changes in cells could be blocked by singlet oxygen scavengers (i.e.,
l-histidine, a-tocopherol), but were not affected by the hydroxyl radical
scavenger mannitol. In addition, we found that SP600125, a JNK-specific
inhibitor, reduced PDT-induced JNK activation as well as caspase-3 activation,
indicating that JNK activity is required for PDT-induced caspase activation.
Collectively, these results demonstrate that singlet oxygen triggers JNK
activation, cytochrome c release, caspase activation and subsequent apoptotic
biochemical changes during PDT and show that curcumin is a potent inhibitor for
this process. Copyright 2004 Wiley-Liss, Inc.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15095415 [PubMed - indexed for MEDLINE]

125: BMC Cancer. 2004 Apr 17;4:13.

Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids.

Limtrakul P, Anuchapreeda S, Buddhasukh D.

Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang
Mai, Thailand. [email protected]

BACKGROUND: Multidrug resistance (MDR) is a phenomenon that is often associated
with decreased intracellular drug accumulation in patient's tumor cells
resulting from enhanced drug efflux. It is related to the overexpression of a
membrane protein, P-glycoprotein (Pgp-170), thereby reducing drug cytotoxicity.
A variety of studies have tried to find MDR modulators which increase drug
accumulation in cancer cells. METHODS: In this study, natural curcuminoids, pure
curcumin, demethoxycurcumin and bisdemethoxycurcumin, isolated from turmeric
(Curcuma longa Linn), were compared for their potential ability to modulate the
human MDR-1 gene expression in multidrug resistant human cervical carcinoma cell
line, KB-V1 by Western blot analysis and RT-PCR. RESULTS: Western blot analysis
and RT-PCR showed that all the three curcuminoids inhibited MDR-1 gene
expression, and bisdemethoxycurcumin produced maximum effect. In additional
studies we found that commercial grade curcuminoid (approximately 77% curcumin,
17% demethoxycurcumin and 3% bisdemthoxycurcumin) decreased MDR-1 gene
expression in a dose dependent manner and had about the same potent inhibitory
effect on MDR-1 gene expression as our natural curcuminoid mixtures. CONCLUSION:
These results indicate that bisdemethoxycurcumin is the most active of the
curcuminoids present in turmeric for modulation of MDR-1 gene. Treatment of drug
resistant KB-V1 cells with curcumin increased their sensitivity to vinblastine,
which was consistent with a decreased MDR-1 gene product, a P-glycoprotein, on
the cell plasma membrane. Although many drugs that prevent the P-glycoprotein
function have been reported, this report describes the inhibition of MDR-1
expression by a phytochemical. The modulation of MDR-1 expression may be an
attractive target for new chemosensitizing agents.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15090070 [PubMed - indexed for MEDLINE]

126: Asian J Androl. 2004 Mar;6(1):71-4.

Contraceptive effect of Curcuma longa (L.) in male albino rat.

Ashok P, Meenakshi B.

Department of Zoology, JNV University, Jodhpur (Raj.) 342 005, India.
[email protected]

AIM: To study the contraceptive effect of the crude extracts of Curcuma longa in
male albino rats. METHODS: Rats were fed orally with Curcuma longa aqueous and
70% alcoholic extract for 60 days (500 mg x kg(-1) x day(-1)). RESULTS: A
reduction in sperm motility and density was observed in both the treated groups.
CONCLUSION: Curcuma longa may have affected the androgen synthesis either by
inhibiting the Leydig cell function or the hypothalamus pituitary axis and as a
result, spermatogenesis is arrested.

PMID: 15064838 [PubMed - indexed for MEDLINE]

127: Biochem Biophys Res Commun. 2004 Apr 16;316(4):1065-72.

Curcumin blocks NF-kappaB and the motogenic response in Helicobacter
pylori-infected epithelial cells.

Foryst-Ludwig A, Neumann M, Schneider-Brachert W, Naumann M.

Institute of Experimental Internal Medicine, Otto-von-Guericke-University,
Leipziger Str. 44, Magdeburg 39120, Germany.

Infection of epithelial cells by the microbial pathogen Helicobacter pylori
leads to activation of the transcription factor nuclear factor kappaB
(NF-kappaB), the induction of pro-inflammatory cytokine/chemokine genes, and the
motogenic response (cell scattering). Here we report that H. pylori-induced
NF-kappaB activation and the subsequent release of interleukin 8 (IL-8) are
inhibited by curcumin (diferuloylmethane), a yellow pigment in turmeric (Curcuma
longa L.). Our results demonstrate that curcumin inhibits IkappaBalpha
degradation, the activity of IkappaB kinases alpha and beta (IKKalpha and beta),
and NF-kappaB DNA-binding. The mitogen-activated protein kinases (MAPK),
extracellular signal-regulated kinases 1/2 (ERK1/2) and p38, which are also
activated by H. pylori infection, were not inhibited by curcumin. Further, the
H. pylori-induced motogenic response was blocked by curcumin. We conclude that
curcumin, due to inhibition of NF-kappaB activation and cell scattering, should
be considered as a potential therapeutic agent effective against pathogenic
processes initiated by H. pylori infection.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15044093 [PubMed - indexed for MEDLINE]

128: Oncogene. 2004 Feb 26;23(8):1599-607.

Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3.

Chendil D, Ranga RS, Meigooni D, Sathishkumar S, Ahmed MM.

Department of Clinical Science, University of Kentucky, Lexington, KY 40536,
USA. [email protected]

Curcumin (Diferuloylmethane) is a major chemical component of turmeric (curcuma
longa) and is used as a spice to give a specific flavor and yellow color in
Asian food. Curcumin exhibits growth inhibitory effects in a broad range of
tumors as well as in TPA-induced skin tumors in mice. This study was undertaken
to investigate the radiosensitizing effects of curcumin in p53 mutant prostate
cancer cell line PC-3. Compared to cells that were irradiated alone
(SF(2)=0.635; D(0)=231 cGy), curcumin at 2 and 4 microM concentrations in
combination with radiation showed significant enhancement to radiation-induced
clonogenic inhibition (SF(2)=0.224: D(0)=97 cGy and SF(2)=0.080: D(0)=38 cGy)
and apoptosis. It has been reported that curcumin inhibits TNF-alpha-induced
NFkappaB activity that is essential for Bcl-2 protein induction. In PC-3 cells,
radiation upregulated TNF-alpha protein leading to an increase in NFkappaB
activity resulting in the induction of Bcl-2 protein. However, curcumin in
combination with radiation treated showed inhibition of TNF-alpha-mediated
NFkappaB activity resulting in bcl-2 protein downregulation. Bax protein levels
remained constant in these cells after radiation or curcumin plus radiation
treatments. However, the downregulation of Bcl-2 and no changes in Bax protein
levels in curcumin plus radiation-treated PC-3 cells, together, altered the Bcl2
: Bax ratio and this caused the enhanced radiosensitization effect. In addition,
significant activation of cytochrome c and caspase-9 and -3 were observed in
curcumin plus radiation treatments. Together, these mechanisms strongly suggest
that the natural compound curcumin is a potent radiosesitizer, and it acts by
overcoming the effects of radiation-induced prosurvival gene expression in
prostate cancer.

Publication Types:
Comparative Study
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 14985701 [PubMed - indexed for MEDLINE]

129: J Med Assoc Thai. 2004 Jan;87(1):87-91.

LacCur stain for detection of mucin in adenocarcinoma.

Wattanasirmkit V, Tanboon J, Shuangshoti S, Shuangshoti S.

Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok
10330, Thailand.

Identification of cytoplasmic mucin, usually by Mayer's mucicarmine stain, is
one of the criteria to diagnose adenocarcinoma. The inexpensive LacCur stain,
made up of Curcuma longa (khamin-shan) and secreta of Laccifer lacca (krang) has
been introduced. The aim of this study was to compare the Mayer's mucicarmine
and LacCur stains in the detection of mucin material. The specimens included 17
adenocarcinomas of the stomach, 16 of the colon, 18 of the lung, 16 of the
breast, and 12 of the bile duct. Squamous cell carcinoma and hepatocellular
carcinoma (altogether 20 cases) were set as negative control. Like Mayer's
mucicarmine, LacCur was capable of detecting of intracytoplasmic mucin in all
adenocarcinomas of the stomach, colon and bile duct, and revealed mucin
substance in 15/18 and 11/16 cases of specimens from the lung and breast,
respectively. The negative control group showed a negative result. Although a
little more time required in preparation, the LacCur stain is simple and very
economical.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 14971540 [PubMed - indexed for MEDLINE]

130: Arch Gerontol Geriatr. 2002 Feb;34(1):37-46.

The curcuma antioxidants: pharmacological effects and prospects for future
clinical use. A review.

Miquel J, Bernd A, Sempere JM, Diaz-Alperi J, Ramirez A.

Department of Biotechnology, University of Alicante, San Vicente, E-03080,
Alicante, Spain. [email protected]

In agreement with the predictions of the oxygen-stress theory of aging and
age-related degenerative diseases, diet supplementation with a number of
phenolic or thiolic antioxidants has been able to increase the life span of
laboratory animals, protect against senescent immune decline and preserve the
respiratory function of aged mitochondria. In addition to the above, more recent
data reviewed here suggest that the polyphenolic compound curcumin and related
non-toxic antioxidants from the rhizome of the spice plant Curcuma longa have a
favorable effect on experimental mouse tumorigenesis as well as on inflammatory
processes such as psoriasis and ethanol-caused hepatic injury. Our own research
has focused on the effects of diet supplementation with an antioxidant-rich
hydroalcoholic extract of the curcuma rhizome on key risk factors of
atherogenesis and related cardiovascular disease. Our reviewed data show that,
in human healthy subjects, the daily intake of 200 mg of the above extract
results in a decrease in total blood lipid peroxides as well as in HDL and
LDL-lipid peroxidation. This anti-atherogenic effect was accompanied by a
curcuma antioxidant-induced normalization of the plasma levels of fibrinogen and
of the apo B/apo A ratio, that may also decrease the cardiovascular risk. The
reviewed literature indicates that curcumin and related plant co-antioxidants
are powerful anti-inflammatory agents. Further, since they potentiate the
anti-atherogenic effect of alpha-tocopherol, more extensive clinical testing of
their probable usefulness in cardiovascular risk reduction seems justified.

PMID: 14764309 [PubMed]

131: Int J Oncol. 2004 Feb;24(2):321-9.

Effect of curcuma on radiation-induced apoptosis in human cancer cells.

Baatout S, Derradji H, Jacquet P, Ooms D, Michaux A, Mergeay M.

Laboratory of Radiobiology, Belgian Nuclear Research Center, SCK-CEN, B-2400
Mol, Belgium. [email protected]

There have been considerable efforts to search for naturally occurring
substances for the intervention of carcinogenesis. Many components from dietary
or medicinal plants have been identified that possess substantial
chemopreventive properties. Curcuma, a yellow pigment from Curcuma longa,
exhibits anti-inflammatory, antitumor, and antioxidative properties. Although
its precise mode of action has not been elucidated so far, studies have shown
that chemopreventive action of curcuma might be due to its ability to induce
apoptosis (programmed cell death) in cancer cells. This original study was
conducted in order to estimate whether curcuma enhances the radiation
sensitivity of cancer cells. For this purpose, curcuma (concentrations ranging
from 0 to 200 microM) was applied to human cancer cell cultures (HeLa, K-562 and
IM-9) with or without X-irradiation (doses comprised between 0 and 8 Gy). Cell
proliferation was monitored by trypan blue exclusion. For the estimation of
apoptosis, changes in cell morphology and flow cytometry analysis (DNA content
and presence of the sub-G1 peak) were performed. Microscopic examination of the
curcuma-treated cells (with concentrations above 100 microM) showed a
characteristic morphology of apoptosis. Furthermore, cells treated with curcuma
exhibited a sub-G1 peak from which the magnitude was proportional to the
concentration of curcuma. X-irradiation alone induced polyploidisation and
apoptosis of the three cell lines, proportional to the doses of irradiation with
a marked difference in radiation sensitivity between the cell lines (IM-9 <
K-562 < HELA). However, when radiation and curcuma were applied together, our
results showed that in HELA, K-562 and IM-9, curcuma showed a radiation
sensitising effect only at the dose of 200 micro M. This result may open a
perspective of synergical therapy at the condition to also address the intrinsic
toxicity of curcuma on normal cells.

PMID: 14719108 [PubMed - indexed for MEDLINE]

132: Biol Pharm Bull. 2004 Jan;27(1):144-6.

Application of single-nucleotide polymorphism analysis of the trnK gene to the
identification of Curcuma plants.

Sasaki Y, Fushimi H, Komatsu K.

Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama
Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.

We previously found that Curcuma plants and drugs derived from Curcuma longa, C.
phaeocaulis, C. zedoaria, and C. aromatica could be identified by the nucleotide
differences at two sites and the existence of a 4-base indel on trnK gene. In
this paper, based on species-specific nucleotide sequences, the application of a
new method, single-nucleotide polymorphism (SNP) analysis was investigated to
identify Curcuma plants more conveniently. First, three types of reverse primer
were synthesized in different lengths, 34 mer, 26 mer, and 30 mer, to anneal the
template DNAs from each species at sites immediately upstream from substitution
positions 177 and 645, and at the site including the 4-base insertion from 728
to 731, respectively. After single-base extension reaction of these primers
using fluorescent-labeled ddNTPs and PCR products of the trnK gene region as
template, the resulting products were detected using an ABI PRISM 310 Genetic
Analyzer. The electrophoretogram showed three or two peaks at different
positions depending on the 27 mer, 31 mer, and 35 mer product lengths. Each peak
was derived from the incorporated fluorescent-labeled ddNMPs complementary to
template nucleotides at positions 645, 724, and 177, respectively. C.
phaeocaulis showed three peaks of ddCMP, ddAMP, and ddAMP. The other three
species showed two peaks derived from 27 mer and 35 mer products: peaks of ddCMP
and ddAMP in C. longa, those of ddCMP and ddTMP in C. zedoaria, and those of
ddTMP and ddAMP in C. aromatica. Thus SNP analysis to identify four Curcuma
plants was newly developed.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 14709921 [PubMed - indexed for MEDLINE]

133: J Biosci. 2003 Dec;28(6):715-21.

Curcumin-induced inhibition of cellular reactive oxygen species generation:
novel therapeutic implications.

Balasubramanyam M, Koteswari AA, Kumar RS, Monickaraj SF, Maheswari JU, Mohan V.

Division of Cell and Molecular Biology, Madras Diabetes Research Foundation, 4
Conran Smith Road, Gopalapuram, Chennai 600 086, India. [email protected]

There is evidence for increased levels of circulating reactive oxygen species
(ROS) in diabetics, as indirectly inferred by the findings of increased lipid
peroxidation and decreased antioxidant status. Direct measurements of
intracellular generation of ROS using fluorescent dyes also demonstrate an
association of oxidative stress with diabetes. Although phenolic compounds
attenuate oxidative stress-related tissue damage, there are concerns over
toxicity of synthetic phenolic antioxidants and this has considerably stimulated
interest in investigating the role of natural phenolics in medicinal
applications. Curcumin (the primary active principle in turmeric, Curcuma longa
Linn.) has been claimed to represent a potential antioxidant and
antiinflammatory agent with phytonutrient and bioprotective properties. However
there are lack of molecular studies to demonstrate its cellular action and
potential molecular targets. In this study the antioxidant effect of curcumin as
a function of changes in cellular ROS generation was tested. Our results clearly
demonstrate that curcumin abolished both phorbol-12 myristate-13 acetate (PMA)
and thapsigargin-induced ROS generation in cells from control and diabetic
subjects. The pattern of these ROS inhibitory effects as a function of
dose-dependency suggests that curcumin mechanistically interferes with protein
kinase C (PKC) and calcium regulation. Simultaneous measurements of ROS and Ca2+
influx suggest that a rise in cytosolic Ca2+ may be a trigger for increased ROS
generation. We suggest that the antioxidant and antiangeogenic actions of
curcumin, as a mechanism of inhibition of Ca2+ entry and PKC activity, should be
further exploited to develop suitable and novel drugs for the treatment of
diabetic retinopathy and other diabetic complications.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 14660871 [PubMed - indexed for MEDLINE]

134: Clin Chim Acta. 2003 Dec;338(1-2):135-41.

Curcumin inhibits protease-activated receptor-2 and -4-mediated mast cell
activation.

Baek OS, Kang OH, Choi YA, Choi SC, Kim TH, Nah YH, Kwon DY, Kim YK, Kim YH, Bae
KH, Lim JP, Lee YM.

Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University,
Iksan, Jeonbuk 570-749, South Korea.

BACKGROUND: Curcumin, a major yellow pigment and active component of turmeric
powder extracted from Curcuma longa L. (Gingiberaceae), has been shown to
possess anti-inflammatory and anti-cancer activities. Protease-activated
receptors (PARs) play a role in inflammation, and human leukemic mast cells
(HMC-1) co-express PAR2 and PAR4. In the present study, the effect of curcumin
on PAR2- and PAR4-mediated HMC-1 activation was examined. METHODS: HMC-1 cells
were stimulated with trypsin (100 nmol/l, PAR2 and PAR4 agonist), SLIGKV-NH(2)
(100 microM, PAR2-activating peptide) or GYPGQV-NH(2) (100 micromol/l
PAR4-activating peptide) in the presence or absence of curcumin (1, 10, and 100
micromol/l). TNF-alpha secretion was measured by enzyme-linked immunosorbent
assay (ELISA). TNF-alpha and tryptase mRNA were measured by
reverse-transcription PCR (RT-PCR). Mitogen-activated protein kinase (MAPK)
activation was assessed by Western blot analysis. Trypsin activity was measured
using the substrate Bz-DL-Arg-p-nitroanilide (BAPNA). RESULTS: Curcumin (10 and
100 micromol/l) inhibited TNF-alpha secretion from trypsin or activating
peptide-stimulated HMC-1. Curcumin (10 and 100 micromol/l) also inhibited
TNF-alpha and tryptase mRNA expression in trypsin-stimulated HMC-1. Furthermore,
curcumin inhibited trypsin-induced extracellular signal-regulated kinase (ERK)
phosphorylation. However, curcumin did not affect the trypsin activity even at
100 micromol/l. CONCLUSION: Curcumin inhibits PAR2- and PAR4-mediated human mast
cell activation, not by inhibition of trypsin activity but by block of ERK
pathway.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 14637278 [PubMed - indexed for MEDLINE]

135: J Agric Food Chem. 2003 Nov 5;51(23):6802-7.

Extraction of essential oil and pigments from Curcuma longa [L] by steam
distillation and extraction with volatile solvents.

Manzan AC, Toniolo FS, Bredow E, Povh NP.

DEQ-CTC-UEM, Avenida Colombo, no. 5790-CEP: 87020-900, Maringa, Parana, Brazil.

Curcuma longa [Linn] (turmeric), of the Zingiberaceae family, has a great
importance in the food, textile, and pharmaceutical industries. The aim of this
work was to identify the best processing conditions to maximize the yields of
essential oil and pigments, as well as their content of ar-turmerone, (alpha and
beta)-turmerone, and the curcuminoids, respectively. Autoclave pressure and
distillation time were the variables studied for the steam distillation process.
The highest yields of essential oil (0.46 wt %) and pigment (0.16 wt
%)-expressed as curcumin, demethoxycurcumin, and bisdemethoxycurcumin-were
obtained at a pressure of 1.0 x 10(5) Pa and a time of 2 h. On the other hand,
with extraction by volatile solvents, the best yield of essential oil (5.49 wt
%) was obtained when using 0.175, 0.124, 0.088 mm particles (Foust, A. S.;
Wenzel, L. A.; Clump, C. W.; Maus, L.; Andersen, L. B. Principios das Operacoes
Unitarias; Editora Guanabara Dois S.A.: Rio de Janeiro, Brazil, 1982), at 40
degrees C, and 6 h of extraction. However, the best yield of pigment (7.98 wt %)
was obtained under the same conditions, except for the temperature (30 degrees
C).

PMID: 14582978 [PubMed - indexed for MEDLINE]

136: J Agric Food Chem. 2003 Oct 22;51(22):6604-11.

Comparison of yield, composition, and antioxidant activity of turmeric (Curcuma
longa L.) extracts obtained using various techniques.

Braga ME, Leal PF, Carvalho JE, Meireles MA.

LASEFI, DEA/FEA (College of Food Engineering), UNICAMP (State University of
Campinas), Caixa Postal 6121, 13083-970 Campinas, SP, Brazil.

Turmeric extracts were obtained from two lots of raw material (M and S) using
various techniques: hydrodistillation, low pressure solvent extraction, Soxhlet,
and supercritical extraction using carbon dioxide and cosolvents. The solvents
and cosolvents tested were ethanol, isopropyl alcohol, and their mixture in
equal proportions. The composition of the extracts was determined by gas
chromatography-flame ionization detection (GC-FID) and UV. The largest yield
(27%, weight) was obtained in the Soxhlet extraction (turmeric (S), ethanol =
1:100); the lowest yield was detected in the hydrodistillation process (2.1%).
For the supercritical extraction, the best cosolvent was a mixture of ethanol
and isopropyl alcohol. Sixty percent of the light fraction of the extracts
consisted of ar-turmerone, (Z)-gamma-atlantone, and (E)-gamma-atlantone, except
for the Soxhlet extracts (1:100, ethanol), for which only ar-turmeronol and
(Z)-alpha-atlantone were detected. The maximum amount of curcuminoids (8.43%)
was obtained using Soxhlet extraction (ethanol/isopropyl alcohol). The Soxhlet
and low pressure extract exhibited the strongest antioxidant activities.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 14558784 [PubMed - indexed for MEDLINE]

137: Biochem Pharmacol. 2003 Oct 15;66(8):1475-83.

Induction of apoptosis by curcumin: mediation by glutathione S-transferase P1-1
inhibition.

Duvoix A, Morceau F, Delhalle S, Schmitz M, Schnekenburger M, Galteau MM, Dicato
M, Diederich M.

Laboratoire de Recherche sur le Cancer et les Maladies du Sang, Centre
Universitaire de Luxembourg, 162A Avenue de la Faiencerie, L-1511 Luxembourg,
Luxembourg.

Expression of glutathione S-transferase P1-1 (GSTP1-1) is correlated to
carcinogenesis and resistance of cancer cells against chemotherapeutic agents.
Curcumin, a natural compound extracted from Curcuma longa, has shown strong
antioxidant and anticancer properties and also the ability to regulate a wide
variety of genes that require activating protein 1 and nuclear factor kappaB
(NF-kappaB) activation. In the present study, we examined the inhibitory effect
of curcumin on the expression of GSTP1-1 mRNA as well as protein, and we
correlated this inhibition with the apoptotic effect of curcumin on K562
leukemia cells. Curcumin efficiently inhibited the tumour necrosis factor alpha-
and phorbol ester-induced binding of AP-1 and NF-kappaB transcription factors to
sites located on the GSTP1-1 gene promoter. TNFalpha-induced GSTP1-1 promoter
activity was also inhibited by curcumin as shown by reporter gene assay. In
parallel, curcumin induced pro-caspases 8 and 9 as well as poly ADP ribose
polymerase cleavage and thus leading to apoptosis in K562 cells. Our results
overall add a novel role for curcumin as this chemoprotective compound could
contribute to induce apoptosis by its ability to inhibit the GSTP1-1 expression
at the level of transcription.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 14555224 [PubMed - indexed for MEDLINE]

138: J Cell Biochem. 2003 Oct 1;90(2):327-38.

Curcumin inhibits UV irradiation-induced oxidative stress and apoptotic
biochemical changes in human epidermoid carcinoma A431 cells.

Chan WH, Wu CC, Yu JS.

Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan
Christian University, Chung Li, Taiwan, Republic of China. [email protected]

Ultraviolet (UV) light is a strong apoptotic trigger that induces
caspase-dependent biochemical changes in cells. Previously we showed that UV
irradiation can activate caspase-3, and the subsequent cleavage and activation
of p21(Cdc42/Rac)-activated kinase 2 (PAK2) in human epidermoid carcinoma A431
cells. In this study we demonstrate that curcumin (Cur), the yellow pigment of
Curcuma longa with known anti-oxidant and anti-inflammatory properties, can
prevent UV irradiation-induced apoptotic changes, including c-Jun N-terminal
kinase (JNK) activation, loss of mitochondrial membrane potential (MMP),
mitochondrial release of cytochrome C, caspase-3 activation, and
cleavage/activation of PAK2 in A431 cells. Flow cytometric analysis using the
cell permeable dye 2',7'-dichlorofluorescin diacetate (DCF-DA) as an indicator
of reactive oxygen species (ROS) generation revealed that the increase in
intracellular oxidative stress caused by UV irradiation could be abolished by
Cur. In addition, we found that SP600125, a JNK-specific inhibitor, reduced UV
irradiation-induced JNK activation as well as caspase-3 activation, indicating
that JNK activity is required for UV irradiation-induced caspase activation.
Collectively, our results demonstrate that Cur significantly attenuates UV
irradiation-induced ROS formation, and suggest that ROS triggers JNK activation,
which in turn causes MMP change, cytochrome C release, caspase activation, and
subsequent apoptotic biochemical changes. Copyright 2003 Wiley-Liss, Inc.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 14505349 [PubMed - indexed for MEDLINE]

139: Nahrung. 2003 Aug;47(4):261-4.

Evaluation of nitric oxide scavenging activity of certain spices in vitro: a
preliminary study.

Baliga MS, Jagetia GC, Rao SK, Babu K.

Department of Radiobiology Kasturba Medical College, Manipal-576 119, Karnataka,
India.

The plant extracts of some commonly used spices were examined for their possible
regulatory effect on nitric oxide (NO) levels using sodium nitroprusside as a NO
donor in vitro. Most of the extracts tested demonstrated direct scavenging of NO
and exhibited significant activity and the potency of scavenging activity was in
the following order: Foeniculum vulgare (aqueous) > Citrus limettiodes > Murraya
koenigii (seed, aqueous) > Murraya koenigii (leaf, aqueous) > Curcuma aromatica
(aqueous) > Murraya koenigii (leaf, dichloromethane:methanol) > Mentha arvensis
(chloroform) > Mentha arvensis (aqueous) > Curcuma longa > Gingko biloba >
Foeniculum vulgare (dichloromethane:methanol) > Zingiber officinale (aqueous) >
Curcuma aromatica (ethanolic) > Murraya koenigii (seed,
dichloromethane:methanol). All the evaluated extracts exhibited a dose-dependent
NO scavenging activity. The aqueous extract of Foeniculum vulgare showed a
greatest NO scavenging effect of 79.75% at 62.5 microg/mL as compared to the
positive control, Gingko biloba where 36.22% scavenging was observed at similar
concentration. The present results suggest that these spices might be potent and
novel therapeutic agents for scavenging of NO and the regulation of pathological
conditions caused by excessive generation of NO and its oxidation product,
peroxynitrite.

Publication Types:
Evaluation Studies
Research Support, Non-U.S. Gov't

PMID: 13678266 [PubMed - indexed for MEDLINE]

140: J Med Assoc Thai. 2003 Jun;86 Suppl 2:S299-309.

Antispasmodic effects of curcuminoids on isolated guinea-pig ileum and rat
uterus.

Itthipanichpong C, Ruangrungsi N, Kemsri W, Sawasdipanich A.

Department of Pharmacology, Faculty of Medicine, Chulalongkorn University,
Bangkok 10330, Thailand.

Curcuminoids, a yellow constituent isolated from Curcuma longa Linn. rhizomes
was studied for its antispasmodic activity in isolated guinea-pig ileum and rat
uterus. Curcuminoids at the concentration of 12 microg/ml significantly
inhibited the ileum pre-contracted with acetylcholine (ACh) 5 x 10(-7) M and
histamine 5 x 10(-7) M. (Force of contraction was 62.84 +/- 4.66% and 75.60 +/-
4.66% respectively) and the effects were prominently observed when the
concentration of curcuminoids was increased to 36 microg/ml. (Force of
contraction was 44.93 +/- 4.33% and 42.79 +/- 1.98%). In potassium depolarizing
Tyrode solution, curcuminoids 4 microg/ml and 20 microg/ml reduced the
contraction induced by calcium chloride (CaCl2) 1.8 mM. (The contraction was
63.31 +/- 1.80% and 36.87 +/- 3.25%). In rat uterus smooth muscle preparation,
curcuminoids 8 microg/ml and 16 microg/ml significantly reduced force and
frequency of contraction induced by oxytocin 1 x 10(-2) IU/ml. Curcuminoids 8
microg/ml produced 54.68 +/- 3.34 per cent force of contraction and 79.09 +/-
2.29 per cent frequency of contraction. Curcuminoids 16 microg/ml caused more
relaxation of rat uterus smooth muscle. (Force of contraction was 43.38 +/-
3.56%, frequency of contraction was 49.96 +/- 5.20%). Curcuminoids 8 and 16
microg/ml significantly reduced force of contraction induced by KCl 50 mM.
(Force of contraction was 54.10 +/- 4.92% and 36.60 +/- 2.99%). The results
obtained from this study concluded that curcuminoids produced a smooth muscle,
relaxation effect on isolated guinea-pig ileum and rat uterus by
receptor-dependent and independent mechanism.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't

PMID: 12930003 [PubMed - indexed for MEDLINE]

141: Nutrition. 2003 Sep;19(9):800-4.

Oral administration of a turmeric extract inhibits erythrocyte and liver
microsome membrane oxidation in rabbits fed with an atherogenic diet.

Mesa MD, Aguilera CM, Ramirez-Tortosa CL, Ramirez-Tortosa MC, Quiles JL, Baro L,
Martinez de Victoria E, Gil A.

Department of Biochemistry and Molecular Biology, Granada, Spain.

OBJECTIVES: The aim of this study was to evaluate the effects of an oral
supplementation with a Curcuma longa ethanol and aqueous extract on the
susceptibility to oxidation of cellular and subcellular membranes affected in
the atherosclerotic process, such as erythrocyte membranes and liver microsomes,
in rabbits fed with a high-fat diet. METHODS: Twenty-four male rabbits were
randomly assigned to one of two groups: group T was treated with a turmeric
hydroalcoholic extract (1.66 mg/kg of body weight) dissolved in a hydroalcoholic
mixture vehicle (7:2), and group C (control): received a curcuma-free
hydroalcoholic solution (7:2). All rabbits had access ad libitum to 150 g/d of
an experimental diet rich in cholesterol and lard to provoke an atherosclerotic
process. Erythrocyte membranes and liver microsomes were isolated, and the
levels of hydroperoxides and thiobarbituric acid-reactive substances were
measured after oxidation induction. RESULTS: The oxidation of erythrocyte
membranes in group T was significantly lower than that in group C, mainly by 30
d (P < 0.05). Levels of hydroperoxides and thiobarbituric acid-reactive
substances in liver microsomes also were significantly lower in group T than in
group C (P < 0.05). CONCLUSIONS: The results of this study indicated that oral
administration of a nutritional dose of C. longa extracts reduces the
susceptibility to oxidation of erythrocyte and liver microsome membranes in
vitro and may contribute to the prevention of effects caused by a diet high in
fat and cholesterol in blood and liver during the development of
atherosclerosis.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12921893 [PubMed - indexed for MEDLINE]

142: Biol Pharm Bull. 2003 Aug;26(8):1135-43.

Effects of curcuma drugs on vasomotion in isolated rat aorta.

Sasaki Y, Goto H, Tohda C, Hatanaka F, Shibahara N, Shimada Y, Terasawa K,
Komatsu K.

Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama
Medical and Pharmaceutical University.

The effectiveness of Curcuma drugs against "Oketsu" and the differences in their
efficacy were evaluated by examining their vasomotional effects as one index.
Since nitric oxide (NO) is the relaxation factor of vascular smooth muscle and
also an inhibitor of platelet aggregation in blood vessels, substances showing
NO-dependent relaxation are thought to be effective in improving Oketsu. In this
study, five Curcuma drugs derived from Curcuma longa, C. kwangsiensis, C.
phaeocaulis, C. wenyujin, and C. zedoaria were used. Methanol extracts exhibited
intense effects on relaxation in rings precontracted by prostaglandin F(2alpha)
(PGF(2alpha)) despite pretreatment with and without N(G)-nitro-l-arginine methyl
ester (L-NAME) as an inhibitor of NO synthesis. The maximal activities were
approximately 80% at 10(-3) g/ml. From these methanol extracts, curcumin and
eight sesquiterpenes were isolated. Since all these compounds showed
NO-independent relaxation effects with almost the same intensities, the
relaxation effects of Curcuma drugs can be estimated by the total amounts of
curcumin and sesquiterpenes. Polysaccharides, the main constituents of
methanol-insoluble compounds of water extracts, in contrast, showed contraction
effects; only polysaccharides in C. zedoaria showed NO-dependent relaxation as
well as contraction. All water extracts showed relaxation effects as sum of the
methanol-soluble compounds-induced relaxation and polysaccharides-induced
contraction. Therefore, all Curcuma drugs tested in the present study can be
effective for vasodilation. Moreover, the drug derived from C. zedoaria has
potential to cure Oketsu with its various acting points.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't

PMID: 12913265 [PubMed - indexed for MEDLINE]

143: Nutr Cancer. 2003;45(2):218-25.

Antitumor activity of extract of Zingiber aromaticum and its bioactive
sesquiterpenoid zerumbone.

Kirana C, McIntosh GH, Record IR, Jones GP.

CSIRO Health Sciences and Nutrition, PO Box 10041, Kintore Avenue, Adelaide DC,
South Australia 5000. [email protected]

The anticancer properties of zerumbone (2,6,9 humulatriene-8-one, a
sesquiterpenoid) from Zingiber aromaticum were compared with those of curcumin
from Curcuma longa in an in vitro MTT tetrazolium salt assay using HT-29,
CaCo-2, and MCF-7 cancer cells and in an azoxymethane (AOM)-induced animal model
of colon cancer using aberrant crypt foci (ACFs) as a preneoplastic marker. The
IC50 of zerumbone was approximately 10 mM and that of curcumin was 25 mM. Cell
cycle arrest in HT-29 cells was observed at G0/G1 for 10 and 12.5 mM and G2/M
for 25 mM after 24 h at concentrations of 10-25 mM of zerumbone, and a
concentration-dependent increase in apoptosis (2-6% of viable cells) was
observed after 48 h using the same concentration range. Male Sprague-Dawley rats
were fed extracts in an AIN diet prepared from the equivalent of 4% by weight of
dried rhizomes of Z. aromaticum and C. longa. ACFs were induced by two doses (15
mg/kg body weight) subcutaneously of AOM 1 wk apart, the rats were killed 10 wk
later, and the ACFs were assessed in the colon. Total ACFs were significantly
reduced by Z. aromaticum extract (down 21%, P < 0.05) relative to control, the
effect being most evident with large ACFs (>3 aberrant crypts per focus).
Similar reductions were observed with 4% C. longa extract in the diet (down 24%,
P < 0.01) and with 2,000 ppm curcumin, the effect being particularly evident
with large ACFs. The concentration of zerumbone in the Z. aromaticum extract
diet was assayed at 300 ppm and of curcumin in the C. longa extract diet was
also 300 ppm, i.e., the extract of C. longa was as effective at one-seventh the
concentration of curcumin as the positive control. Zerumbone is effective as an
anticancer agent, possibly by its apoptosis-inducing and antiproliferative
influences. This latter possibility is currently being investigated.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12881017 [PubMed - indexed for MEDLINE]

144: Planta Med. 2003 Jun;69(6):584-6.

Authentication of Panax notoginseng by 5S-rRNA spacer domain and random
amplified polymorphic DNA (RAPD) analysis.

Cui XM, Lo CK, Yip KL, Dong TT, Tsim KW.

Department of Biology and Biotechnology Research Institute, The Hong Kong
University of Science and Technology, Hong Kong, P. R. China.

The great majority of Panax species are well-known herbal medicines in the
Orient, and many of them share a close resemblance in appearance and chemical
composition. Among these Panax species, the root of P. notoginseng (Sanqi) is a
unique herb that has distinct clinical usage. Here, the 5S-rRNA spacer domains
were isolated from P. notoginseng, P. japonicus var. major, P. stipuleanatus, P.
quinquefolius, P. ginseng, P. zingiberensis, and P. wangianus, and four common
adulterants of P. notoginseng including Curcuma wenyujin, Curcuma longa,
Bletilla striata and Gynura segetum. The spacer domains were sequenced and
compared, which showed over 75 % DNA identity among all Panax species, but not
for the adulterants. In addition, random amplification of polymorphic DNA (RAPD)
analysis was used to distinguish different members of Panax genus as well as the
morphological variants of P. notoginseng. These molecular methods could be used
in the authentic identification of P. notoginseng from other Panax species.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12865989 [PubMed - indexed for MEDLINE]

145: Planta Med. 2003 Jun;69(6):523-6.

Effects of baicalein, berberine, curcumin and hesperidin on mucin release from
airway goblet cells.

Lee CJ, Lee JH, Seok JH, Hur GM, Park YC, Seol IC, Kim YH.

Department of Pharmacology, College of Medicine, Chungnam National University,
Daejeon, Korea. [email protected]

Baicalein, berberine, curcumin and hesperidin are the major components derived
from Scutellaria baicalensis, Coptis japonica, Curcuma longa and Poncirus
trifoliata, respectively. These plants have been used for the treatment of
diverse chronic inflammatory diseases including respiratory disease in oriental
medicine and their respective major components were reported to have various
biological effects including anti-inflammatory activity. In the present study,
we investigated whether these four natural products affect mucin release from
airway goblet cells and compared the possible activities of these agents with
the inhibitory action on mucin release by PLL and the stimulatory action by ATP.
Confluent primary hamster tracheal surface epithelial (HTSE) cells were
metabolically radiolabeled using 3H-glucosamine for 24 h and chased for 30 min
in the presence of varying concentrations of each agent to assess the effects on
3H-mucin release. The results were as follows: (i) baicalein did not affect
mucin release significantly; (ii) berberine, curcumin and hesperidin increased
mucin release at the highest concentration (10 - 4 M); (iii) PLL inhibited and
ATP increased mucin release. We conclude that berberine, curcumin and hesperidin
can increase mucin release by directly acting on airway mucin-secreting cells
and suggest that these agents be further studied for possible use as mild
expectorants during the treatment of chronic airway diseases. Abbreviations.
PLL:poly- L-lysine ATP:adenosine triphosphate HTSE:hamster tracheal surface
epithelial DMSO:dimethylsulfoxide IL-12:interleukin-12 PBS:phosphate-buffered
saline

PMID: 12865970 [PubMed - indexed for MEDLINE]

146: J Ethnopharmacol. 2003 Aug;87(2-3):241-6.

Screening of antimutagenicity via antioxidant activity in Cuban medicinal
plants.

Ramos A, Visozo A, Piloto J, Garcia A, Rodriguez CA, Rivero R.

Centro de Investigacion y Desarrollo de Medicamentos, Avenue 26, No. 1605,
Ciudad de La Habana, Nuevo Vedado, CP 10600, Cuba. [email protected]

The reducing activity on the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical,
z.rad;OH radical scavenging potential, in vitro inhibition of lipid peroxidation
and modulation of mutagenicity induced by ter-butyl hydroperoxide (TBH) in
Escherichia coli were sequentially screened in 45 species of plants used with
medicinal purposes in Cuba, in a search for antioxidant agents which protect DNA
against oxidative stress.Five species, e.g. Tamarindus indica L., Lippia alba
L., Pimenta dioica (L.) Merr, Rheedia aristata Griseb. and Curcuma longa L.
displayed IC(50)<30 micro g/ml in the DPPH radical reduction assay and IC(50)<32
micro g/ml in lipid peroxidation inhibition testing. Pimenta dioica and Curcuma
longa L. showed also a 20% inhibition of the in vitro induced z.rad;OH attack to
deoxyglucose. Further antimutagenesis assay in Escherichia coli IC 188 evidenced
that only Pimenta dioica prevents DNA damage by TBH to the test bacteria. A role
of antioxidant enzymes is presumed in this case, as judged by a different
response in the isogenic Escherichia coli IC 203 deficient in catalase and alkyl
hydroperoxide reductase and the discrete inhibition of oxidative mutagenesis
also observed when pre-treatment of the extract was assayed. Eugenol, the main
constituent of the essential oil of Pimenta dioica, also inhibited oxidative
mutagenesis by TBH in Escherichia coli, at concentrations ranging from 150 to
400 micro g/plate.

PMID: 12860316 [PubMed - indexed for MEDLINE]

147: Carcinogenesis. 2003 Sep;24(9):1515-24. Epub 2003 Jul 4.

Curcumin inhibits phorbol ester-induced expression of cyclooxygenase-2 in mouse
skin through suppression of extracellular signal-regulated kinase activity and
NF-kappaB activation.

Chun KS, Keum YS, Han SS, Song YS, Kim SH, Surh YJ.

College of Pharmacy, College of Medicine, Seoul National University, Seoul
151-741, South Korea.

Recently, there have been considerable efforts to search for naturally occurring
substances for the intervention of carcinogenesis. Many components derived from
dietary or medicinal plants have been found to possess substantial
chemopreventive properties. Curcumin, a yellow coloring ingredient of turmeric
(Curcuma longa L., Zingiberaceae), has been shown to inhibit experimental
carcinogenesis and mutagenesis, but molecular mechanisms underlying its
chemopreventive activities remain unclear. In the present work, we assessed the
effects of curcumin on 12-O- tetradecanoylphorbol-13-acetate (TPA)-induced
expression of cyclooxygenase-2 (COX-2) in female ICR mouse skin. Topical
application of the dorsal skin of female ICR mice with 10 nmol TPA led to
maximal induction of cox-2 mRNA and protein expression at approximately 1 and 4
h, respectively. When applied topically onto shaven backs of mice 30 min prior
to TPA, curcumin inhibited the expression of COX-2 protein in a dose-related
manner. Immunohistochemical analysis of TPA-treated mouse skin revealed enhanced
expression of COX-2 localized primarily in epidermal layer, which was markedly
suppressed by curcumin pre-treatment. Curcumin treatment attenuated TPA-
stimulated NF-kappaB activation in mouse skin, which was associated with its
blockade of degradation of the inhibitory protein IkappaBalpha and also of
subsequent translocation of the p65 subunit to nucleus. TPA treatment resulted
in rapid activation via phosphorylation of extracellular signal-regulated kinase
(ERK)1/2 and p38 mitogen-activated protein (MAP) kinases, which are upstream of
NF-kappaB. The MEK1/2 inhibitor U0126 strongly inhibited NF-kappaB activation,
while p38 inhibitor SB203580 failed to block TPA-induced NF-kappaB activation in
mouse skin. Furthermore, U0126 blocked the IkappaBalpha phosphorylation by TPA,
thereby blocking the nuclear translocation of NF-kappaB. Curcumin inhibited the
catalytic activity of ERK1/2 in mouse skin. Taken together, suppression of COX-2
expression by inhibiting ERK activity and NF-kappaB activation may represent
molecular mechanisms underlying previously reported antitumor promoting effects
of this phytochemical in mouse skin tumorigenesis.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12844482 [PubMed - indexed for MEDLINE]

148: Biol Pharm Bull. 2003 Jul;26(7):1021-4.

Curcumin attenuates allergen-induced airway hyperresponsiveness in sensitized
guinea pigs.

Ram A, Das M, Ghosh B.

Molecular Immunology and Immunogenetics Laboratory, Institute of Genomics and
Integrative Biology, Delhi University Campus, India.

Anti-asthmatic property of curcumin (diferuloylmethane), a natural product from
the rhizomes of Curcuma longa, has been tested in a guinea pig model of airway
hyperresponsiveness. We sensitized guinea pigs with ovalbumin (OVA) to develop
certain characteristic features of asthma: allergen induced airway constriction
and airway hyperreactivity to histamine. Guinea pigs were treated with curcumin
during sensitization (to examine its preventive effect) or after developing
impaired airways features (to examine its therapeutic effect). Status of airway
constriction and airway hyperreactivity were determined by measuring specific
airway conductance (SGaw) using a non-invasive technique, constant-volume body
plethysmography. Curcumin (20 mg/kg body weight) treatment significantly
inhibits OVA-induced airway constriction (p<0.0399) and airway hyperreactivity
(p<0.0043). The results demonstrate that curcumin is effective in improving the
impaired airways features in the OVA-sensitized guinea pigs.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 12843631 [PubMed - indexed for MEDLINE]

149: J Pharm Pharmacol. 2003 Jun;55(6):847-53.

Antioxidant activity of Smoke Shield in-vitro and in-vivo.

Sreekanth KS, Sabu MC, Varghese L, Manesh C, Kuttan G, Kuttan R.

Amala Cancer Research Centre, Amala Nagar, Thrissur 680 553, Kerala, India.

Smoke Shield is a proprietory formulation containing extract of turmeric
(Curcuma longa), obtained by supercritical carbon dioxide gas extraction and
post-supercritical hydroethanolic extraction, together with extracts of green
tea and other spices whose presence synergistically increases the activity of
turmeric. This study evaluates the antioxidant potentials of Smoke Shield
in-vitro and in experimental animals, as well as in human models. Smoke Shield
was found to scavenge superoxide radicals generated by photoreduction of
riboflavin (50% inhibitory concentration = 91 microg mL(-1)) and hydroxyl
radicals generated by Fenton reaction (50% inhibitory concentration = 95 microg
mL(-1)) and reduced lipid peroxidation. Administration of Smoke Shield to mice
was found to elevate antioxidant enzymes such as catalase and superoxide
dismutase in blood as well as in liver and kidney. Glutathione-S-transferase
activity was found to be significantly elevated in liver and kidney of animals
treated with Smoke Shield. Glutathione levels were also significantly elevated
in blood. Glutathione reductase was significantly elevated in kidney.
Administration of Smoke Shield decreased the lipid peroxidation in serum, liver
and kidney, as well as reduced the levels of conjugated dienes and
hydroperoxides. Administration of Smoke Shield to smokers was found to increase
the superoxide dismutase and glutathione in blood and decrease glutathione
peroxidase. Smoke Shield inhibited phase I enzymes as represented by
aniline-hydroxylase and aminopyrenedemethylase in-vitro. These results indicate
that Smoke Shield has potent antioxidant activity, could inhibit phase I enzymes
and increase detoxifying enzymes, which makes it an effective chemoprotective
herbal formulation.

PMID: 12841947 [PubMed - indexed for MEDLINE]

150: Plant Cell Rep. 2003 Jul;21(11):1054-9. Epub 2003 Apr 26.

High-frequency shoot multiplication in Curcuma longa L using thidiazuron.

Prathanturarug S, Soonthornchareonnon N, Chuakul W, Phaidee Y, Saralamp P.

Department of Pharmaceutical Botany, Faculty of Pharmacy, Mahidol University,
447 Sri-ayudthaya Road, 10400, Bangkok, Thailand. [email protected]

The effects of plant growth regulators, explant types, and culture regimens were
investigated on in vitro shoot proliferation from terminal bud explants of
Curcuma longa. Each bud was longitudinally divided into four equal pieces, each
1 cm in length, and used as explants. These were then cultured on MS medium
supplemented with 18.17 microM thidiazuron for 4 weeks prior to transfer to MS
medium without growth regulator for 8 weeks. Under these conditions, a shoot
induction rate of 18.22+/-0.62 shoots/explant was obtained after 12 weeks of
cultures. Spontaneous rooting was achieved. The regenerated plants were
transferred to soil under greenhouse conditions and subsequently grown
successfully in the field.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12835998 [PubMed - indexed for MEDLINE]

151: J Pharm Pharmacol. 2003 May;55(5):593-601.

Erratum in:
J Pharm Pharmacol. 2003 Aug;55(8):1175.

Efficacy and irritancy of enhancers on the in-vitro and in-vivo percutaneous
absorption of curcumin.

Fang JY, Hung CF, Chiu HC, Wang JJ, Chan TF.

Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung
University, Tao-Yuan, Taiwan. [email protected]

Curcumin is a predominant compound derived from the rhizomes of Curcuma longa
L., and shows antibacterial, anti-inflammatory and antineoplastic activity. The
in-vitro and in-vivo skin absorption of curcumin was investigated after
application of enhancers using Wistar rat as an animal model. The enhancers
selected in this study included terpenes, flavonoids and cholestanol. The
irritant profiles of these enhancers were also established by transepidermal
water loss (TEWL) and histological observations. Cyclic monoterpenes generally
showed stronger enhancement of curcumin permeation than the other enhancers.
Modulation of concentration and pretreatment duration of enhancers possibly
indicated that the enhancers have varied ability and mechanisms to enhance
curcumin permeation. Terpineol produced the highest TEWL values among the
enhancers tested, whereas ketocholestanol produced no, or only a negligible,
increase in TEWL as compared with control. The results showed that skin
disruption and inflammation did not necessarily correspond to the enhancing
efficiency of the enhancers.

Publication Types:
In Vitro

PMID: 12831501 [PubMed - indexed for MEDLINE]

152: Nutr Cancer. 2003;45(1):53-9.

Suppression of altered hepatic foci development by curcumin in wistar rats.

Shukla Y, Arora A.

Environmental Carcinogenesis Division, Industrial Toxicology Research Centre,
Lucknow - 226 001, India. [email protected]

Curcumin, a yellow pigment of turmeric (Curcuma longa), is a commonly used spice
and a coloring agent in foods, drugs, and cosmetics. Curcumin is known to
possess chemopreventive properties in various animal tumor models. In the
present study the effect of curcumin on the development of altered hepatic foci
(AHF), by using a medium term liver bioassay, has been evaluated. AHF were
analyzed by quantitative stereology using the Leica Qwin Image Analysis system
from frozen liver sections stained for g-glutamyl transferase, adenosine
triphosphatase, glucose-6-phosphatase, alkaline phosphatase, and placental
isozyme of glutathione S-transferase. A significant protection on
diethylnitrosamine (DEN) initiated and 2-acetylaminofluorene (AAF) promoted AHF
by curcumin was observed on these biological markers. The curcumin
administration was found to restore the normal levels of the enzymes glutathione
S-transferase and g-glutamyl transferase in rat liver following DEN-AAF
exposure. Similarly, a significant protection was provided by curcumin in the
enzyme-deficient foci for the adenosine triphosphatase-, alkaline phosphatase-,
and glucose-6-phosphatase-treated groups in comparison to the DEN-AAF-treated
group. These results show that curcumin can effectively suppress the DEN-induced
development of AHF in rat liver.

PMID: 12791505 [PubMed - indexed for MEDLINE]

153: Phytother Res. 2003 May;17(5):481-4.

In vitro peroxynitrite scavenging activity of diarylheptanoids from Curcuma
longa.

Kim JE, Kim AR, Chung HY, Han SY, Kim BS, Choi JS.

Faculty of Food Science and Biotechnology, Pukyong National University, Korea.

Peroxynitrite is a cytotoxic intermediate produced by the reaction between the
superoxide anion (O(2)) and nitric oxide (NO). The aim of this study was to
investigate the scavenging effects of Curcuma longa L. on authentic
peroxynitrite, and further studies are planned that will attempt to identify the
active principles from the active fractions. The methanolic extract of C. longa
showed 50% scavenging activity (IC(50)) at concentration of 1.7 +/- 0.08 micro
g/ml, and was thus fractionated with several solvents. The peroxynitrite
scavenging activity potential of the individual fraction was in the order of
ethyl acetate > dichloromethane > water fraction. The ethyl acetate soluble
fraction exhibiting strong scavenging activity was further purified by repeated
silica gel column chromatography. Peroxynitrite scavenging diarylheptanoids,
curcumin I (1), curcumin II (2), and curcumin III (3) were isolated as active
principles. Compounds 1-3 showed the peroxynitrite scavenging activities with
IC(50) values of 4.0 +/- 0.04, 6.4 +/- 0.30, and 29.7 +/- 1.29 micro M,
respectively. Penicillamine as positive control exhibited IC(50) value of 2.38
+/- 0.34 micro M. The structure-activity relationship of diarylheptanoids on
peroxynitrite was also discussed. Copyright 2003 John Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12748983 [PubMed - indexed for MEDLINE]

154: Biol Pharm Bull. 2003 May;26(5):725-8.

Cytoprotective and cytotoxic effects of curcumin: dual action on H2O2-induced
oxidative cell damage in NG108-15 cells.

Mahakunakorn P, Tohda M, Murakami Y, Matsumoto K, Watanabe H, Vajaragupta O.

Department of Pharmacology, Institute of Natural Medicine, Toyama Medical and
Pharmaceutical University, Sugitani, Japan.

The ability of curcumin, a natural antioxidant isolated from Curcuma longa, to
inhibit hydrogen peroxide (H(2)O(2))-induced cell damage in NG108-15 cells was
examined. When added simultaneously with 500 microM H(2)O(2), curcumin (25-100
microM) effectively protected cells from oxidative damage. However, when the
cells were pretreated with curcumin (25-100 microM) for 1.5 h before H(2)O(2)
exposure, curcumin was unable to inhibit H(2)O(2)-induced cell damage. Instead,
it caused a significant concentration-dependent decrease in cell viability after
H(2)O(2) exposure. This dual action of curcumin suggests that pretreatment with
curcumin by itself did not have any significant effect on the viability of the
NG108-15 cells, but it sensitized them to oxidative damage induced by H(2)O(2)
under our experimental conditions. It appears that these events may not relate
to the antioxidant and free radical scavenging activities of curcumin.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12736521 [PubMed - indexed for MEDLINE]

155: Pharmacol Toxicol. 2003 Jan;92(1):33-8.

Dietary supplementation of curcumin enhances antioxidant and phase II
metabolizing enzymes in ddY male mice: possible role in protection against
chemical carcinogenesis and toxicity.

Iqbal M, Sharma SD, Okazaki Y, Fujisawa M, Okada S.

Department of Pathological Research, Faculty of Medicine, Okayama University
Graduate School of Medicine and Dentistry, 2-5-1 Shikata-Cho, Okayama 700-8558,
Japan. [email protected]

Dietary antioxidants protect laboratory animals against the induction of tumours
by a variety of chemical carcinogens. Among possible mechanism of protection
against chemical carcinogenesis could be mediated via-antioxidant-dependent
induction of detoxifying enzymes. Curcumin, a yellow pigment from Curcuma longa,
is a major component of turmeric and is commonly used as a spice and food
colouring material and exhibits antiinflammatory antitumour, and antioxidant
properties. In this study we therefore investigated the effect of dietary
supplementation of curcumin on the activities of antioxidant and phase
II-metabolizing enzymes involved in detoxification, and production of reactive
oxygen species were quantified in ddY male mice. Dietary supplementation of
curcumin (2%, w/v) to male ddY mice for 30 days significantly increased the
activities of glutathione peroxidase, glutathione reductase, glucose-6-phosphate
dehydrogenase and catalase to 189%, 179%, 189%, and 181% in liver and 143%,
134%, 167% and 115% in kidney respectively as compared with corresponding normal
diet fed control (P<0.05-0.001). Parallel to these changes, curcumin feeding to
mice also resulted in a considerable enhancement in the activity of phase
II-metabolizing enzymes viz. glutathione S-transferase and quinone reductase to
1.7 and 1.8 times in liver and 1.1 and 1.3 times in kidney respectively as
compared with corresponding normal diet fed control (P<0.05-0.01). In general,
the increase in activities of antioxidant and phase II-metabolizing enzymes was
more pronounced in liver as compared to kidney. The induction of such
detoxifying enzymes by curcumin suggest the potential value of this compound as
protective agent against chemical carcinogenesis and other forms of
electrophilic toxicity. The significance of these results can be implicated in
relation to cancer chemopreventive effects of curcumin against the induction of
tumours in various target organs.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12710595 [PubMed - indexed for MEDLINE]

156: J Agric Food Chem. 2003 Apr 23;51(9):2520-5.

Functional properties of spice extracts obtained via supercritical fluid
extraction.

Leal PF, Braga ME, Sato DN, Carvalho JE, Marques MO, Meireles MA.

LASEFI-DEA/FEA-UNICAMP (State University of Campinas), Caixa Postal 6121,
13083-970 Campinas, Sao Paulo, Brazil.

In the present study the antioxidant, anticancer, and antimycobacterial
activities of extracts from ginger (Zingiber officinale Roscoe), rosemary
(Rosmarinus officinalis L.), and turmeric (Curcuma longa L.) were evaluated. The
extracts were obtained using supercritical CO(2) with and without ethanol and/or
isopropyl alcohol as cosolvent. The extracts' antioxidant power was assessed
using the reaction between beta-carotene and linolenic acid, the
antimycobacterial activity against M. tuberculosis was measured by the MABA
test, and their anticancer action was tested against nine human cancer
ancestries: lung, breast, breast resistant, melanoma, colon, prostate, leukemia,
and kidney. The rosemary extracts exhibited the strongest antioxidant and the
lowest antimycobacterial activities. Turmeric extracts showed the greatest
antimycobacterial activity. Ginger and turmeric extracts showed selective
anticancer activities.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12696930 [PubMed - indexed for MEDLINE]

157: Anticancer Res. 2003 Jan-Feb;23(1A):363-98.

Anticancer potential of curcumin: preclinical and clinical studies.

Aggarwal BB, Kumar A, Bharti AC.

Cytokine Research Section, Department of Bioimmunotherapy, University of Texas
M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 143, Houston, TX,
USA. [email protected]

Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma
longa, commonly called turmeric. Extensive research over the last 50 years has
indicated this polyphenol can both prevent and treat cancer. The anticancer
potential of curcumin stems from its ability to suppress proliferation of a wide
variety of tumor cells, down-regulate transcription factors NF-kappa B, AP-1 and
Egr-1; down-regulate the expression of COX2, LOX, NOS, MMP-9, uPA, TNF,
chemokines, cell surface adhesion molecules and cyclin D1; down-regulate growth
factor receptors (such as EGFR and HER2); and inhibit the activity of c-Jun
N-terminal kinase, protein tyrosine kinases and protein serine/threonine
kinases. In several systems, curcumin has been described as a potent antioxidant
and anti-inflammatory agent. Evidence has also been presented to suggest that
curcumin can suppress tumor initiation, promotion and metastasis.
Pharmacologically, curcumin has been found to be safe. Human clinical trials
indicated no dose-limiting toxicity when administered at doses up to 10 g/day.
All of these studies suggest that curcumin has enormous potential in the
prevention and therapy of cancer. The current review describes in detail the
data supporting these studies.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 12680238 [PubMed - indexed for MEDLINE]

158: J Ethnopharmacol. 2003 May;86(1):113-6.

Lens aldose reductase inhibiting potential of some indigenous plants.

Halder N, Joshi S, Gupta SK.

Department of Pharmacology, All India Institute of Medical Sciences, Ansari
Nagar, New Delhi 110029, India.

Cataract is the leading cause of blindness worldover. Diabetes is one of the
major risk factors for cataractogenesis and aldose reductase (AR) has been
reported to play an important role in sugar-induced cataract. In the present
study, the AR inhibitory activity of Ocimum sanctum (OS), Withania somnifera
(WS), Curcuma longa (CL), Azadirachta indica (AI) were studied together with
their effect on sugar-induced cataractogenic changes in rat lenses in vitro.
Aqueous extracts of the plants, procured from Dabur, India, were reconstituted
with double distilled water to make various dilutions. AR inhibitory activity of
these extracts and their anticataract potentials were evaluated in vitro in rat
lenses. AR inhibitory activity of the aqueous extract of different plants was
calculated considering the AR activity of normal rat lenses as 100%. The
concentration of the plant extract that showed maximum AR inhibitory activity
was selected to further study its effect on galactose-induced lens swelling and
polyol accumulation in vitro. All the four plants were found to inhibit lens AR
activity but to different extent. From dose-response curve, OS was found to be
the most effective AR inhibitor followed by CL, AI and WS. The IC(50) values of
OS, CL, AI and WS were calculated to be 20, 55, 57 and 89 microg/ml,
respectively. OS showed a significant inhibition (38.05%) in polyol accumulation
followed by CL and AI (28.4 and 25.04%, respectively). WS did not show any
effect on polyol level in rat lenses. None of the plant extracts showed any
significant effect on lens water content.OS possesses a significant anticataract
activity in vitro and its anticataract potential could be related with its AR
inhibitory effect.

PMID: 12686449 [PubMed - indexed for MEDLINE]

159: J Environ Pathol Toxicol Oncol. 2003;22(1):49-58.

Curcumin exhibits antimetastatic properties by modulating integrin receptors,
collagenase activity, and expression of Nm23 and E-cadherin.

Ray S, Chattopadhyay N, Mitra A, Siddiqi M, Chatterjee A.

Department of Receptor Biology and Tumor Metastasis, Chittaranjan National
Cancer Institute, Calcutta, India.

Curcumin (diferuloyl methane), the major pigment from the rhizome of Curcuma
longa L., has been widely studied for its tumor-inhibiting properties. Recent
studies indicate that curcumin can modify cell receptor binding, it also affects
intracellular signalling reactions. Curcumin-treated B16F10 melanoma cells
formed eight-fold fewer lung metastases in C57BL6 mice. In the cell adhesion
assays, curcumin-treated cells showed a dose-dependent reduction in their
binding to four extracellular matrix (ECM) proteins. The binding to fibronectin,
vitronectin, and collagen IV decreased by over 50% in 24 hours, and by 100%
after 48 hours of curcumin treatment, it persisted at this level even after 15
days of cultivating cells in curcumin-free medium. Curcumin-treated cells showed
a marked reduction in the expression of alpha5beta1 and alpha(v)beta3 integrin
receptors. In addition, curcumin treatment inhibited pp125 focal adhesion kinase
(FAK), tyrosine phosphorylation of a 120 kD protein, and collagenase activity.
Curcumin enhances the expression of antimetastatic proteins, tissue inhibitor
metalloproteinase (TIMP)-2, nonmetastatic gene 23 (Nm23), and E-cadherin. In
this article we report on the effect of curcumin on the expression of integrin,
TIMP-2, Nm23, E-cadherin, adhesion, and metalloproteinase activity.

PMID: 12678405 [PubMed - indexed for MEDLINE]

160: J Altern Complement Med. 2003 Feb;9(1):161-8.

Safety and anti-inflammatory activity of curcumin: a component of tumeric
(Curcuma longa).

Chainani-Wu N.

Department of Stomatology, University of California, San Francisco, CA
94143-0658, USA. [email protected]

INTRODUCTION: Tumeric is a spice that comes from the root Curcuma longa, a
member of the ginger family, Zingaberaceae. In Ayurveda (Indian traditional
medicine), tumeric has been used for its medicinal properties for various
indications and through different routes of administration, including topically,
orally, and by inhalation. Curcuminoids are components of tumeric, which include
mainly curcumin (diferuloyl methane), demethoxycurcumin, and
bisdemethoxycurcmin. OBJECTIVES: The goal of this systematic review of the
literature was to summarize the literature on the safety and anti-inflammatory
activity of curcumin. METHODS: A search of the computerized database MEDLINE
(1966 to January 2002), a manual search of bibliographies of papers identified
through MEDLINE, and an Internet search using multiple search engines for
references on this topic was conducted. The PDR for Herbal Medicines, and four
textbooks on herbal medicine and their bibliographies were also searched.
RESULTS: A large number of studies on curcumin were identified. These included
studies on the antioxidant, anti-inflammatory, antiviral, and antifungal
properties of curcuminoids. Studies on the toxicity and anti-inflammatory
properties of curcumin have included in vitro, animal, and human studies. A
phase 1 human trial with 25 subjects using up to 8000 mg of curcumin per day for
3 months found no toxicity from curcumin. Five other human trials using
1125-2500 mg of curcumin per day have also found it to be safe. These human
studies have found some evidence of anti-inflammatory activity of curcumin. The
laboratory studies have identified a number of different molecules involved in
inflammation that are inhibited by curcumin including phospholipase,
lipooxygenase, cyclooxygenase 2, leukotrienes, thromboxane, prostaglandins,
nitric oxide, collagenase, elastase, hyaluronidase, monocyte chemoattractant
protein-1 (MCP-1), interferon-inducible protein, tumor necrosis factor (TNF),
and interleukin-12 (IL-12). CONCLUSIONS: Curcumin has been demonstrated to be
safe in six human trials and has demonstrated anti-inflammatory activity. It may
exert its anti-inflammatory activity by inhibition of a number of different
molecules that play a role in inflammation.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 12676044 [PubMed - indexed for MEDLINE]

161: Phytomedicine. 2003 Jan;10(1):34-8.

Inhibition of Propionibacterium acnes-induced mediators of inflammation by
Indian herbs.

Jain A, Basal E.

Department of Microbiology, King George's Medical College, Lucknow, India.
[email protected]

Propionibacterium acnes, an anaerobic pathogen, plays an important role in the
pathogenesis of acne by inducing certain inflammatory mediators. These mediators
include reactive oxygen species (ROS) and pro-inflammatory cytokines. In the
present study, ROS, interleukin-8 (IL-8) and tumor necrosis factor-alpha
(TNF-alpha) were used as the major criteria for the evaluation of
anti-inflammatory activity. To prove the anti-inflammatory effects of herbs,
polymorphonuclear leukocytes (PMNL) and monocytes were treated with culture
supernatant of P. acnes in the presence or absence of herbs. It was found that
Rubia cordifolia, Curcuma longa, Hemidesmus indicus, and Azadirachta indica
caused a statistically significant suppression of ROS from PMNL. Sphaeranthus
indicus caused a smaller, still significant suppression of ROS. Aloe vera had no
effect on ROS production. In the case of proinflammatory cytokine-induced
monocytes, maximum suppression was shown by Azadirachta indica and Sphaeranthus
indicus, followed by Hemidesmus indicus, Rubia cordifolia, and Curcuma longa.
Aloe vera showed insignificant inhibitory activity. Thus, these herbs shows
anti-inflammatory activity by suppressing the capacity of P. acnes-induced ROS
and pro-inflammatory cytokines, the two important inflammatory mediators in acne
pathogenesis.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12622461 [PubMed - indexed for MEDLINE]

162: J Agric Food Chem. 2003 Mar 12;51(6):1578-81.

Fungicidal property of Curcuma longa L. rhizome-derived curcumin against
phytopathogenic fungi in a greenhouse.

Kim MK, Choi GJ, Lee HS.

Faculty of Biotechnology and Institute of Agricultural Science & Technology,
College of Agriculture, Chonbuk National University, Chonju 561-756, South
Korea.

Fungicidal activity of Curcuma longa rhizome-derived materials against Botrytis
cineria, Erysiphe graminis, Phytophthora infestans, Puccinia recondita,
Pyricularia oryzae, and Rhizoctonia solani was tested using a whole plant method
in vivo. It was compared with synthetic fungicides and four commercially
available compounds derived from C. longa. The response varied with the tested
plant pathogen. At 1000 mg/L, the hexane extract of C. longa showed fungicidal
activities against E.graminis, P. infestans, and R. solani, and the ethyl
acetate extract of C. longa showed fungicidal activities against B. cineria, P.
infestans, Pu. recondita, and R. solani. Curcumin was isolated from the ethyl
acetate fraction using chromatographic techniques and showed fungicidal
activities against P. infestans, Pu. recondita, and R. solani with 100, 100, and
63% control values at 500 mg/L and 85, 76, and 45% control values at 250 mg/L,
respectively. In the test with components derived from C. longa, turmerone
exhibited weak activity against E. graminis, but no activity was observed from
treatments with borneol, 1,8-cineole, sabinene, and turmerone. In comparison,
potent fungicidal activity with chlorothalonil against P. infestans at 50 mg/L
and dichlofluanid against B. cinerea at 50 mg/L was exhibited. These results may
be an indication of at least one of the fungicidal actions of curcumin derived
from C. longa.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12617587 [PubMed - indexed for MEDLINE]

163: Teratog Carcinog Mutagen. 2003;Suppl 1:151-60.

In vitro curcumin modulates ferric nitrilotriacetate (Fe-NTA) and hydrogen
peroxide (H2O2)-induced peroxidation of microsomal membrane lipids and DNA
damage.

Iqbal M, Okazaki Y, Okada S.

Department of Pathological Research, Faculty of Medicine, Okayama University
Graduate School of Medicine and Dentistry, Okayama, Japan. [email protected]

A number of investigations have implicated the involvement of free radicals in
various pathogenic process including initiation/promotion stages of
carcinogenesis and antioxidants have been considered to be a protective agent
for this reason. An iron chelate, ferric nitrilotriacetate (Fe-NTA), is a potent
nephrotoxic agent and induces acute and subacute renal proximal tubular necrosis
by catalyzing the decomposition of hydrogen peroxide-derived production of
hydroxyl radicals, which are known to cause lipid peroxidation and DNA damage.
The latter is associated with a high incidence of renal adenocarcinoma in
rodents. Lipid peroxidation and DNA damage are the principal manifestation of
Fe-NTA-induced toxicity, which could be mitigated by antioxidants. In this
study, we therefore investigated the effect of curcumin, a polyphenolic compound
from Curcuma longa for a possible protection against lipid peroxidation and DNA
damage induced by Fe-NTA and hydrogen peroxide in vitro. Incubation of renal
microsomal membrane/and or calf thymus DNA with hydrogen peroxide (40 mM) in the
presence of Fe-NTA (0.1 mM) induces renal microsomal lipid peroxidation and DNA
damage to about 2.2-and 5.6-fold, respectively, as compared to saline treated
control (P<0.001). Induction of renal microsomal lipid peroxidation and DNA
damage was modulated by curcumin dose dependently. In lipid peroxidation
protection studies, curcumin treatment showed a dose-dependent strong inhibition
(18-80% inhibition, P<0.05-0.001) of Fe-NTA and hydrogen peroxide-induced lipid
peroxidation as measured by MDA formation in renal microsomes. Similarly, in
DNA-sugar damage protection studies, curcumin treatment also showed a dose
dependent inhibition (22-57% inhibition, P<0.05-0.001) of DNA-sugar damage. From
these studies, it was concluded that curcumin modulates Fe-NTA and hydrogen
peroxide-induced peroxidation of microsomal membrane lipids and DNA damage.
Curcumin might, therefore, be a suitable candidate for the chemoprevention of
Fe-NTA-associated cancer. Copyright 2003 Wiley-Liss, Inc.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12616605 [PubMed - indexed for MEDLINE]

164: Bioorg Med Chem. 2003 Mar 20;11(6):1057-63.

Curcumin differentially modulates mRNA profiles in Jurkat T and human peripheral
blood mononuclear cells.

Gertsch J, Guttinger M, Heilmann J, Sticher O.

Swiss Federal Institute of Technology Zurich, Institute of Pharmaceutical
Sciences, Winterthurerstrasse 190, 8057 Zurich, Switzerland.

Curcumin, the yellow pigment of the rhizome of Curcuma longa is known to inhibit
the transcription factors AP-1, Egr-1, NF-kappaB, c-myc and several important
signaling kinases. We therefore investigated the differential effects of
curcumin in concentation between 1.5 and 13.6 microM on gene expression in T
Jurkat CD4(+) and human peripheral blood mononuclear cells (PBMCs). Relative
quantification with reverse transcription real-time PCR (RT-rt-PCR) showed that
low concentrations of curcumin significantly down-regulated mitogen-induced
granulocyte macrophage colony stimulating factor (GM-CSF) mRNA (3- to 5-fold at
3 microM) in a dose- and time-dependent manner in both cell types. In
comparison, the down-regulation of inducible nitric oxide (iNOS) mRNA levels was
less pronounced, but interferon gamma (IFN-gamma) mRNA was dose-dependently
up-regulated with curcumin concentrations up to 8.2 microM. Cyclin D1 mRNA
expression was specifically inhibited in Jurkat T cells and stimulated PBMCs.
The transcription factors NF-kappaB and NF-ATc were not affected in PBMCs.
Interleukin-2 (IL-2), and-6 (IL-6) mRNAs levels were not influenced markedly by
curcumin in stimulated PBMCs, but significantly reduced in stimulated Jurkat T
cells. In addition, cytotoxic effects and down-regulation of mRNAs, including
p65 and the house-keeping genes could only be measured in Jurkat T cells. These
findings confirm previous reports on the anti-neoplastic potential of curcumin
and show that this compound differentially modulates the expression profile of
Th1 cells and PBMCs.

Publication Types:
In Vitro

PMID: 12614893 [PubMed - indexed for MEDLINE]

165: Zhong Yao Cai. 2002 Mar;25(3):184-5.

[Study on the effect of Rhizoma Curcuma Longa on gastrin receptor]

[Article in Chinese]

Xiao X, Zhao Y, Yuan H, Xia W, Zhao J, Wang X.

Department of Pharmacy, 302 Hospital of PLA, Beijing 100039.

By the method of receptor combination, effects of the active constituents in
Rhizoma Curcuma Longa and Radix Curcumae were studied. The results showed that
Rhizoma Curcuma Longa probably include the excitant or antagonist of gastrin
receptor. And the inhibitory intensity was shown as followed: parts of ethyl
acetate > parts of methanol > parts of ether > parts of volatile oil, root tuber
> rhizome.

Publication Types:
Comparative Study
English Abstract

PMID: 12583161 [PubMed - indexed for MEDLINE]

166: Anticancer Res. 2002 Nov-Dec;22(6C):4179-81.

Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori,
a group 1 carcinogen.

Mahady GB, Pendland SL, Yun G, Lu ZZ.

Department of Pharmacy Practice, College of Pharmacy, WHO Collaborating Centre
for Traditional Medicine, University of Illinois at Chicago, Chicago, IL 60612,
USA. [email protected]

BACKGROUND: Curcumin, a polyphenolic chemical constituent derived from turmeric
(Curcuma longa), has been shown to prevent gastric and colon cancers in rodents.
Many mechanisms have been proposed for the chemopreventative effects, although
the effect of curcumin on the growth of Helicobacter pylori has not been
reported. H. pylori is a Group 1 carcinogen and is associated with the
development of gastric and colon cancer. MATERIALS AND METHODS: A methanol
extract of the dried powdered turmeric rhizome and curcumin were tested against
19 strains of H. pylori, including 5 cagA+ strains. RESULTS: Both the methanol
extract and curcumin inhibited the growth of all strains of H. pylori in vitro
with a minimum inhibitory concentration range of 6.25-50 micrograms/ml.
CONCLUSION: These data demonstrate that curcumin inhibits the growth of H.
pylori cagA+ strains in vitro, and this may be one of the mechanisms by which
curcumin exerts its chemopreventative effects.

Publication Types:
Research Support, U.S. Gov't, P.H.S.

PMID: 12553052 [PubMed - indexed for MEDLINE]

167: Mol Cancer Ther. 2003 Jan;2(1):95-103.

Curcumin (diferuloyl-methane) enhances tumor necrosis factor-related
apoptosis-inducing ligand-induced apoptosis in LNCaP prostate cancer cells.

Deeb D, Xu YX, Jiang H, Gao X, Janakiraman N, Chapman RA, Gautam SC.

Division of Hematology/Medical Oncology, Department of Neurology, Henry Ford
Health System, Detroit, Michigan 48202, USA.

The role of natural food products in prevention of prostate cancer has been
confirmed in recent epidemiological studies; however, the mechanism of
chemoprevention by the dietary constituents largely remains unknown. Curcumin,
the yellow pigment and active component of turmeric (Curcuma longa), exhibits
chemopreventive and growth inhibitory activity against several tumor cell lines.
The androgen-sensitive human prostate cancer cell line LNCaP is only slightly
susceptible to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL),
a member of the tumor necrosis factor family of cell death-inducing ligands. In
this study, we investigated whether curcumin and TRAIL cooperatively interact to
promote death of LNCaP cells. At low concentrations (10 micro M curcumin and 20
ng/ml TRAIL), neither of the two agents alone produced significant cytotoxicity
(curcumin, <10%; TRAIL, approximately 15%) in LNCaP cells, as measured by the
3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfonyl)-2H-tetra
zolium dye reduction assay. On the other hand, cell death was markedly enhanced
(2-3-fold) if tumor cells were treated with curcumin and TRAIL together. The
combined curcumin and TRAIL treatment increased the number of hypodiploid cells
and induced DNA fragmentation in LNCaP cells. The combined treatment induced
cleavage of procaspase-3, procaspase-8, and procaspase-9, truncation of Bid, and
release of cytochrome c from the mitochondria, indicating that both the
extrinsic (receptor-mediated) and intrinsic (chemical-induced) pathways of
apoptosis are triggered in prostate cancer cells treated with a combination of
curcumin and TRAIL. These results define a potential use of curcumin to
sensitize prostate cancer cells for TRAIL-mediated immunotherapy.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

PMID: 12533677 [PubMed - indexed for MEDLINE]

168: Biofactors. 2002;16(1-2):29-43.

Curcumin differentially regulates TGF-beta1, its receptors and nitric oxide
synthase during impaired wound healing.

Mani H, Sidhu GS, Kumari R, Gaddipati JP, Seth P, Maheshwari RK.

Department of Pathology, Uniformed Services University of the Health Sciences,
Bethesda, MD 20814, USA.

Wound healing is a highly ordered process, requiring complex and coordinated
interactions involving peptide growth factors of which transforming growth
factor-beta (TGF-beta) is one of the most important. Nitric oxide is also an
important factor in healing and its production is regulated by inducible nitric
oxide synthase (iNOS). We have earlier shown that curcumin (diferuloylmethane),
a natural product obtained from the plant Curcuma longa, enhances cutaneous
wound healing in normal and diabetic rats. In this study, we have investigated
the effect of curcumin treatment by topical application in
dexamethasone-impaired cutaneous healing in a full thickness punch wound model
in rats. We assessed healing in terms of histology, morphometry, and
collagenization on the fourth and seventh days post-wounding and analyzed the
regulation of TGF-beta1, its receptors type I (tIrc) and type II (tIIrc) and
iNOS. Curcumin significantly accelerated healing of wounds with or without
dexamethasone treatment as revealed by a reduction in the wound width and gap
length compared to controls. Curcumin treatment resulted in the enhanced
expression of TGF-beta1 and TGF-beta tIIrc in both normal and impaired healing
wounds as revealed by immunohistochemistry. Macrophages in the wound bed showed
an enhanced expression of TGF-beta1 mRNA in curcumin treated wounds as evidenced
by in situ hybridization. However, enhanced expression of TGF-beta tIrc by
curcumin treatment observed only in dexamethasone-impaired wounds at the 7th day
post-wounding. iNOS levels were increased following curcumin treatment in
unimpaired wounds, but not so in the dexamethasone-impaired wounds. The study
indicates an enhancement in dexamethasone impaired wound repair by topical
curcumin and its differential regulatory effect on TGF-beta1, it's receptors and
iNOS in this cutaneous wound-healing model.

Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 12515914 [PubMed - indexed for MEDLINE]

169: Indian J Physiol Pharmacol. 2002 Apr;46(2):209-17.

Biodegradable microspheres of curcumin for treatment of inflammation.

Kumar V, Lewis SA, Mutalik S, Shenoy DB, Venkatesh, Udupa N.

Department of Pharmaceutics, College of Pharmaceutical Sciences, Manipal-576
119.

Curcumin, a natural constituent of Curcuma longa (turmeric, CAS 458-37-7) was
formulated as prolonged release biodegradable microspheres for treatment of
inflammation. Natural biodegradable polymers, namely, bovine serum albumin and
chitosan were used to encapsulate curcumin to form a depot forming drug delivery
system. Microspheres were prepared by emulsion-solvent evaporation method
coupled with chemical cross-linking of the natural polymers. Curcumin could be
encapsulated into the biodegradable carriers upto an extent of 79.49 and 39.66%
respectively with albumin and chitosan. Different drug:polymer ratios did not
affect the mean particle size or particle size distribution significantly.
However, the concentration of the crosslinking agent had remarkable influence on
the drug release. In-vitro release studies indicated a biphasic drug release
pattern, characterized by a typical burst-effect followed by a slow release
which continued for several days. Evaluation of antinflammatory activity using
Freund's adjuvant induced arthritic model in Wistar rats revealed significant
difference between both the formulations, albumin microspheres and chitosan
micropheres as well as against control. It was evident from the present study
that the curcumin biodegradable microspheres could be successfully employed as
prolonged release drug delivery system for better therapeutic management of
inflammation as compared to oral or subcutaneous route.

Publication Types:
Comparative Study

PMID: 12500496 [PubMed - indexed for MEDLINE]

170: Biol Pharm Bull. 2002 Dec;25(12):1593-9.

Sequence analysis of Chinese and Japanese Curcuma drugs on the 18S rRNA gene and
trnK gene and the application of amplification-refractory mutation system
analysis for their authentication.

Sasaki Y, Fushimi H, Cao H, Cai SQ, Komatsu K.

Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama
Medical and Pharmaceutical University, Sugitani, Japan.

The botanical origins of Chinese and Japanese Curcuma drugs were determined to
be Curcuma longa, C. phaeocaulis, the Japanese population of C. zedoaria, C.
kwangsiensis, C. wenyujin, and C. aromatica based on a comparison of their 18S
rRNA gene and trnK gene sequences with those of six Curcuma species reported
previously. Moreover, to develop a more convenient identification method,
amplification-refractory mutation system (ARMS) analysis of both gene regions
was performed on plants. The ARMS method for the 18S rRNA gene was established
using two types of forward primers designed based on the nucleotide difference
at position 234. When DNAs of four Curcuma species were used as templates, PCR
amplification with either of the two primers only generated a fragment of 912
base pairs (bp). However, when DNAs of the purple-cloud type of C. kwangsiensis
and C. wenyujin were used, PCR amplifications with both primers unexpectedly
generated the fragment, suggesting that these two were heterozygotes. The ARMS
method for the trnK gene was also established using a mixture of four types of
specific reverse primers designed on the basis of base substitutions and indels
among six species, and common reverse and forward primers. C. phaeocaulis or the
Chinese population of C. zedoaria, the Japanese population of C. zedoaria or the
purple-cloud type of C. kwangsiensis, the pubescent type of C. kwangsiensis or
C. wenyujin, and C. aromatica were found to show specific fragments of 730, 185,
527 or 528, and 641 or 642 bp, respectively. All species including C. longa also
showed a common fragment of 897-904 bp. Using both ARMS methods, together with
information on producing areas, the identification of Curcuma plants was
achieved. Moreover, the ARMS method for the trnK gene was also useful for
authentication of Curcuma drugs.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 12499646 [PubMed - indexed for MEDLINE]

171: Vet Hum Toxicol. 2002 Dec;44(6):334-8.

Kinetics of venom and antivenom serum and clinical parameters and treatment
efficacy in Bothrops alternatus envenomed dogs.

Jacome D, Melo MM, Santos MM, Heneine LG.

Federal University of Minas Gerais, School of Veterinary Medicine, Department of
Clinics, POB 567, CEP:30 1 23-970, Belo Horizonte, MG, Brazil.

Dogs envenomed with non-lethal doses of Bothrops alternatus venom received
standard antivenom therapy, im injections of flunixin meglumine, or topical
treatmentwith aqueous Curcuma longa plant extract. Biodistribution of the venom
and antivenom were determined by ELISA. There was no significant difference in
the efficacy of antivenom and plant extract on local effects; flunixin treatment
had lower efficacy. Distribution of the venom was similar with all 3 treatments.
Serum levels of the antivenom reached maximum 2-4 h after administration and
were not detected after the 5th d.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12458635 [PubMed - indexed for MEDLINE]

172: J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jan 5;783(1):287-95.

Curcumin in plasma and urine: quantitation by high-performance liquid
chromatography.

Heath DD, Pruitt MA, Brenner DE, Rock CL.

UCSD Cancer Prevention and Control Program, Comprehensive Cancer Center,
University of California, 9500 Gilman Drive, Dept. 0901, San Diego, 92093-0901,
La Jolla, CA, USA. [email protected]

Curcumin, a derivative of the plant Curcuma longa, is used extensively in the
food industry. It is a major component of curry powder, and research has shown
that curcumin may prevent cancer and other chronic diseases. We have developed a
robust automated analytical method for the determination of curcumin in plasma
and urine. The method involves extracting the curcumin from 0.2 ml sample volume
with ethyl acetate/methanol organic solvents, and use of an internal standard,
beta-17-estradiol acetate. Analysis utilizes a reversed-phase C(18) column and
UV detection at 262 nm. Performance characteristics have been assessed. The
assay is linear from 0.2 to 7.0 microgram/ml. The coefficient of variation for
intra- and inter-day assays is <7.5%. The average recovery of curcumin from
plasma and urine is greater than 96%. The data presented in this report
demonstrate that the method provides rapid, sensitive, precise and accurate
measurements of curcumin concentrations in plasma and urine.

PMID: 12450549 [PubMed - indexed for MEDLINE]

173: J Ethnopharmacol. 2002 Nov;83(1-2):161-5.

Antidepressant activity of aqueous extracts of Curcuma longa in mice.

Yu ZF, Kong LD, Chen Y.

Institute of Functional Biomolecule, School of Life Sciences, Nanjing
University, Nanjing 210093, China.

Curcuma longa (turmeric) is a well-known indigenous herbal medicine. The aqueous
extracts, when administered orally to the mice from 140 to 560 mg/kg for 14
days, were able to elicit dose-dependent relation of immobility reduction in the
tail suspension test and the forced swimming test in mice. The effects of the
extracts at the dose of 560 mg/kg were more potent than that of reference
antidepressant fluoxetine. The extracts, at the dose of 140 mg/kg or above for
14 days, significantly inhibited the monoamine oxidize A (MAO) activity in mouse
whole brain at a dose-dependent manner, however, oral administration of the
extract only at a dose of 560 mg/kg produced observable MAO B inhibitory
activity in animal brain. Fluoxetine showed only a tendency to inhibit MAO A and
B activity in animal brain in the study. Neither the extracts of C. longa nor
fluoxetine, at the doses tested, produced significant effects on locomotor
activity. These results demonstrated that C. longa had specifically
antidepressant effects in vivo. The activity of C. longa in antidepression may
mediated in part through MAO A inhibition in mouse brain.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12413724 [PubMed - indexed for MEDLINE]

174: J Ethnopharmacol. 2002 Nov;83(1-2):153-9.

Evaluation of natural products on inhibition of inducible cyclooxygenase (COX-2)
and nitric oxide synthase (iNOS) in cultured mouse macrophage cells.

Hong CH, Hur SK, Oh OJ, Kim SS, Nam KA, Lee SK.

Department of Pharmacy, College of Pharmacy, Ewha Womans University, 11-1
Daehyun-dong, Seodaemun-ku, 120-750, Seoul, South Korea.

The inhibitors of prostaglandin biosynthesis and nitric oxide production have
been considered as potential anti-inflammatory and cancer chemopreventive
agents. In this study, we evaluated approximately 170 methanol extracts of
natural products including Korean herbal medicines for the inhibition of
prostaglandin E(2) production (for COX-2 inhibitors) and nitric oxide formation
(for iNOS inhibitors) in lipopolysaccharide (LPS)-induced mouse macrophages
RAW264.7 cells. As a result, several extracts such as Aristolochia debilis,
Cinnamomum cassia, Cinnamomum loureirii, Curcuma zedoaria, Eugenia
caryophyllata, Pterocarpus santalius, Rehmania glutinosa and Tribulus terrestris
showed potent inhibition of COX-2 activity (>80% inhibition at the test
concentration of 10 micro g/ml). In addition, the extracts of A. debilis,
Caesalpinia sappan, Curcuma longa, C. zedoaria, Daphne genkwa and Morus alba
were also considered as potential inhibitors of iNOS activity (>70% inhibition
at the test concentration of 10 micro g/ml). These active extracts mediating
COX-2 and iNOS inhibitory activities are warranted for further elucidation of
active principles for development of new cancer chemopreventive and/or
anti-inflammatory agents.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12413723 [PubMed - indexed for MEDLINE]

175: Altern Med Rev. 2002 Oct;7(5):404-9.

Nutritional support for chronic myelogenous and other leukemias: a review of the
scientific literature.

Steriti R.

Chronic myelogenous leukemia (CML) is a slowly progressive disease characterized
by the overproduction of granulocytes (neutrophils, eosinophils, and basophils).
A blood smear shows moderate elevations in white blood cell counts that may
persist for years and be benign. Platelets are increased in number, although
their function is impaired, resulting in symptoms of easy bleeding (purpura,
swollen gums). Conventional medical treatment is a marrow transplant and
alkylating agents, which are usually prescribed only during crisis. Several
nutrients and botanicals have been studied for use in CML, including vitamin A
and all-trans retinoic acid (Retin-A), vitamin D3, vitamin E, vitamin B12,
indirubin (found in herbs including Indigofera tinctoria and Isatis tinctoria),
and Curcuma longa. This article briefly reviews the scientific literature on the
therapeutic use of these nutrients for CML.

Publication Types:
Review

PMID: 12410624 [PubMed - indexed for MEDLINE]

176: Arzneimittelforschung. 2002;52(9):695-8.

Total synthesis and anti-leishmanial activity of some curcumin analogues.

Gomes Dde C, Alegrio LV, Leon LL, de Lima ME.

Universidade Federal Rural do Rio de Janeiro, Departamento de Quimica-Instituto
de Ciencias Exatas, Seropedica, RJ, Brazil.

Curcumin (1) an important yellow dye isolated from Curcuma longa rhizomes,
exhibits a variety of pharmacological effects such as anti-inflammatory,
antioxidant and antiviral activity. Ten curcuminoids (2-11) were synthesized by
the condensation of 2,4-pentanedione with differently substituted benzaldehydes,
using the boron complex approach, which avoided Knoevenagel condensation at C-3
of the diketone. The curcuminoids were assayed in vitro against Leishmania
amazonensis promastigotes using pentamidine isethionate (CAS 140-64-7) as the
reference drug. Compound (5)
1,7-bis-(2-hydroxy-4-methoxyphenyl)-1,6-heptadiene-3,5-dione) was the most
effective.

PMID: 12404885 [PubMed - indexed for MEDLINE]

177: J Nat Prod. 2002 Sep;65(9):1227-31.

Discovery of natural products from Curcuma longa that protect cells from
beta-amyloid insult: a drug discovery effort against Alzheimer's disease.

Park SY, Kim DS.

Program for Collaborative Research in Pharmaceutical Sciences and Department of
Medicinal Chemistry and Pharmacognosy (m/c 877), College of Pharmacy, University
of Illinois at Chicago, 60612, USA.

From Curcuma longa, two novel compounds, 4' '-(3' "-methoxy-4'
"-hydroxyphenyl)-2' '-oxo-3' '-enebutanyl
3-(3'-methoxy-4'hydroxyphenyl)propenoate (calebin-A, 1) and
1,7-bis(4-hydroxy-3-methoxyphenyl)-1,4,6-heptatrien-3-one (2), and seven known
compounds, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione
(curcumin, 3),
1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione
(demethoxycurcumin, 4), 1,7-bis(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione
(bisdemethoxycurcumin, 5),
1-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-6-heptene-3,5-dione (6),
1,7-bis(4-hydroxyphenyl)-1-heptene-3,5-dione (7),
1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (8), and
1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one (9), were isolated
following a bioassay-guided fractionation scheme utilizing an assay to detect
protection of PC12 cells from beta-amyloid insult. Compounds 1, 3-5, and 7 were
found to more effectively protect PC12 cells from betaA insult (ED(50) = 0.5-10
microg/mL) than Congo red (10) (ED(50) = 37-39 microg/mL).

PMID: 12350137 [PubMed - indexed for MEDLINE]

178: J Biochem Mol Biol. 2002 May 31;35(3):337-42.

Curcumin suppresses activation of NF-kappaB and AP-1 induced by phorbol ester in
cultured human promyelocytic leukemia cells.

Han SS, Keum YS, Seo HJ, Surh YJ.

Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul
National University, Seoul 151-742, South Korea.

Many components that are derived from medicinal or dietary plants possess
potential chemopreventive properties. Curcumin, a yellow coloring agent from
turmeric (Curcuma longa Linn, Zingiberaceae), possesses strong antimutagenic and
anticarcinogenic activities. In this study, we have found that curcumin inhibits
the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced nuclear factor kB
(NF-kappaB) activation by preventing the degradation of the inhibitory protein
IkBalpa; and the subsequent translocation of the p65 subunit in cultured human
promyelocytic leukemia (HL-60) cells. Alternatively, curcumin repressed the
TPA-induced activation of NF-kappaB through direct interruption of the binding
of NF-kappaB to its consensus DNA sequences. Likewise, the TPA-induced DNA
binding of the activator protein-1 (AP-1) was inhibited by curcumin
pretreatment.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12297018 [PubMed - indexed for MEDLINE]

179: Zhongguo Zhong Yao Za Zhi. 1999 Dec;24(12):718-21, 763.

[A study on soil suitability for growth of rhizome of Curcuma longa L.]

[Article in Chinese]

Li L, Zhang Y, Song H.

Chongqing Academy of Chinese Materia Medica, Chongqing 400065.

OBJECTIVE: To seek for the type of soil that influences favorably the yield and
quality of Curcuma longa. METHOD: Field contrast control experiment, correlation
analysis, path analysis and cluster analysis were used. RESULT: The rhizome
yield and quality of Curcuma longa. varied greatly with the types of soil
texture. There are clear correlations among the soil factors, as well as between
the soil factors and the rhizome yield and quality of the plant. A regression
equation of the rhizome yield and soil factors has been built up. CONCLUSION:
The soil suitable for growing Curcuma longa. can be classified into three types
according to the results of correlation analysis and cluster analysis.

Publication Types:
English Abstract

PMID: 12205979 [PubMed - indexed for MEDLINE]

180: Zhongguo Zhong Yao Za Zhi. 1999 Oct;24(10):589-90, 637.

[Effect of growth period, storage time and varieties on the contents of main
active constituents of Curcuma longa L. in rhizome]

[Article in Chinese]

Li L, Fu S, Qing S.

Chongqing Academy of Chinese Materia Medica, Chongqing 400065.

OBJECTIVE: To provide criteria for selection, storage and cultivation of the
rhizome of Curcuma longa. METHOD: Field observation and sample analysis on the
rhizome. RESULT: The contents of curcuminoids and essential oils in mother and
daughter rhizome went up with the progress of plant development. The contents of
curcuminoids reached the maximum in early September and early October. The
contents of essential oils in mother rhizome reached the maximum in early
September. The contents of curcuminoids and essential oils in the rhizome varied
with the species and went down with the increase of storage years. CONCLUSION:
The rhizome should be collected when leaves of the plant have just withered. The
suitable storage time is three years.

Publication Types:
English Abstract

PMID: 12205954 [PubMed - indexed for MEDLINE]

181: Zhongguo Zhong Yao Za Zhi. 1999 Sep;24(9):531-3, 574.

[Effects of cultivating measures on rhizome yield and some main active
constituents of Curcuma longa L.]

[Article in Chinese]

Li L, Zhang Y.

Chongqing Academy of Chinese Materia Medica, Chongqing 400065.

OBJECTIVE: To substantiate the effects of cultivating measures on the rhizome
yield and main active constituents of Curcuma longa. METHOD: Randomized block
design was applied to the study of the sowing time and plant density, and
orthogonal experiment L9 (3(4)) was conducted to determine the quantity of
fertilizer. RESULT: The effects of cultivating measures on the rhizome yield and
some main active constituents of Curcuma longa were noticeable. The rhizome
yield went up, and the contents of curcuminoids and essential oils went down
with the increase of fertilizer application. CONCLUSION: The main cultivating
measures for high-yield and good-quality of rhizome: rational sowing time-late
March, plant population-12 checkrows per m2, 1 mother rhizome per checkrow. The
suitable fertilizer requirements have also been formulated.

Publication Types:
English Abstract

PMID: 12205897 [PubMed - indexed for MEDLINE]

182: Zhongguo Zhong Yao Za Zhi. 1999 Nov;24(11):654-7, 701.

[A study on fresh rhizome simulation model and its application to comprehensive
agronomic measures for good quality and high yield of Curcuma longa L.]

[Article in Chinese]

Li L, Song H, Zhang Y, Fu S.

Chongqing Academy of Chinese Materia, Chongqing 400065.

OBJECTIVE: To work out standardized cultivating measures for Curcuma longa
according to the analysis of fresh rhizome simulation model. METHOD: Second
order orthogonal rotative regression design. RESULT: The fresh rhizome
simulation model was built up, and 5 main measures that affect fresh rhizome
yield were analyzed by the mathematical model of five unknowns second order
orthogonal rotative regression. Sowing time, plant population and potassium play
an important role in raising the fresh rhizome yield. Sowing time is clearly
interrelated with plant population, and plant population is clearly interrelated
with the fertilizer used Sufficient N and K are necessary for raising the yield.
There is a clear interrelation among the fertilizer factors. CONCLUSION: Optimal
farming measures: sowing time March 1-17, and plant population-110,000 to
115,000 mother rhizomes per hm2. The optimal fertilizer requirements have also
been formulated.

Publication Types:
English Abstract

PMID: 12212083 [PubMed - indexed for MEDLINE]

183: Arterioscler Thromb Vasc Biol. 2002 Jul 1;22(7):1225-31.

Curcuma longa extract supplementation reduces oxidative stress and attenuates
aortic fatty streak development in rabbits.

Quiles JL, Mesa MD, Ramirez-Tortosa CL, Aguilera CM, Battino M, Gil A,
Ramirez-Tortosa MC.

Department of Physiology, Granada University, Granada, Spain.

OBJECTIVE: This study evaluates the effect of a Curcuma longa extract on the
development of experimental atherosclerosis (fatty streak) in rabbits and its
interaction with other plasmatic antioxidants. METHODS AND RESULTS: Two
experimental groups of male New Zealand White rabbits, a control group and a
curcuma-extract (CU) group, were fed an atherogenic diet. Additionally, the CU
group received an oral curcuma hydroalcoholic extract. Six animals from each
experimental group were killed after 10, 20, and 30 days. Compared with the CU
group, the control group showed significantly higher plasma lipid peroxide at
all experimental times (10, 20, and 30 days) and significantly lower
alpha-tocopherol and coenzyme Q levels at 20 and 30 days. Histological results
for the fatty streak lesions revealed damage in the thoracic and abdominal aorta
that was significantly lower in the CU group than in the control group at 30
days. CONCLUSIONS: Supplementation with Curcuma longa reduces oxidative stress
and attenuates the development of fatty streaks in rabbits fed a high
cholesterol diet.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12117742 [PubMed - indexed for MEDLINE]

184: Biochem Biophys Res Commun. 2002 Jul 5;295(1):62-6.

Curcumin (diferuloylmethane), a singlet oxygen ((1)O(2)) quencher.

Das KC, Das CK.

Department of Molecular Biology, University of Texas Health Center at Tyler,
11937 US Hwy 271, Tyler, TX 75708, USA. [email protected]

Curcumin (diferuloylmethane) is a major component of food flavoring turmeric
(Curcuma longa), and has been reported to be anticarcinogenic and
anti-inflammatory. Although curcumin was shown to have antioxidant properties,
its exact antioxidant nature has not been fully investigated. In this report we
have investigated the possible antioxidant properties of curcumin using EPR
spectroscopic techniques. Curcumin was found to inhibit the (1)O(2)-dependent
2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) formation in a dose-dependent
manner. (1)O(2) was produced in a photosensitizing system using rose bengal as
sensitizer, and was detected as TEMP-(1)O(2) adducts by electron paramagnetic
resonance (EPR) spectroscopic techniques using TEMP as a spin-trap. Curcumin at
2.75 microM caused 50% inhibition of TEMP-(1)O(2) adduct formation. However,
curcumin only marginally inhibited (24% maximum at 80 microM) reduction of
ferricytochrome c in a xanthine-xanthine oxidase system demonstrating that it is
not an effective superoxide radical scavenger. Additionally, there was minor
inhibition of DMPO-OH adduct formation by curcumin (solubilized in ethanol) when
an ethanol control was included in the EPR spin-trapping study, suggesting that
curcumin may not be an effective hydroxyl radical scavenger. Together these data
demonstrate that curcumin is able only to effectively quench singlet oxygen at
very low concentration in aqueous systems. (c) 2002 Elsevier Science (USA).

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12083767 [PubMed - indexed for MEDLINE]

185: Food Chem Toxicol. 2002 Aug;40(8):1091-7.

Anti-tumor promoting potential of selected spice ingredients with antioxidative
and anti-inflammatory activities: a short review.

Surh YJ.

Laboratory of Biochemistry and Molecular Toxicology, College of Pharmacy, Seoul
National University, 151-742, Seoul, South Korea. [email protected]

A wide variety of phenolic substances derived from spice possess potent
antimutagenic and anticarcinogenic activities. Examples are curcumin, a yellow
colouring agent, contained in turmeric (Curcuma longa L., Zingiberaceae),
[6]-gingerol, a pungent ingredient present in ginger (Zingiber officinale
Roscoe, Zingiberaceae) and capsaicin, a principal pungent principle of hot chili
pepper (Capsicum annuum L, Solanaceae). The chemopreventive effects exerted by
these phytochemicals are often associated with their antioxidative and
anti-inflammatory activities. Cyclo-oxygenase-2 (COX-2) has been recognized as a
molecular target of many chemopreventive as well as anti-inflammatory agents.
Recent studies have shown that COX-2 is regulated by the eukaryotic
transcription factor NF-kappaB. This short review summarizes the molecular
mechanisms underlying chemopreventive effects of the aforementioned spice
ingredients in terms of their effects on intracellular signaling cascades,
particularly those involving NF-kappaB and mitogen-activated protein kinases.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 12067569 [PubMed - indexed for MEDLINE]

186: Int J Radiat Oncol Biol Phys. 2002 Jul 1;53(3):735-43.

Radioprotective action of curcumin extracted from Curcuma longa LINN: inhibitory
effect on formation of urinary 8-hydroxy-2'-deoxyguanosine, tumorigenesis, but
not mortality, induced by gamma-ray irradiation.

Inano H, Onoda M.

Redox Regulation Research Group, Research Center for Radiation Safety, National
Institute of Radiological Sciences, 9-1 Anagawa-4-chome, Inage-ku, Chiba-shi
263-8555, Japan. [email protected]

PURPOSE: We evaluated the radioprotective action of curcumin
[1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] extracted from
Curcuma longa LINN against the acute and chronic effects and the mortality
induced by exposure to radiation using female rats. METHODS AND MATERIALS: For
the assay of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine, a marker for acute
effects, Wistar-MS virgin rats were fed the basal diet with exposure at 0 or 3
Gy to gamma-rays from a 60Co source as the control. Rats in the experimental
groups received whole-body irradiation with 3 Gy and were fed a diet containing
1% (wt/wt) curcumin for 3 days before and/or 2 days after irradiation. The urine
was collected for a 24-h period between 1 and 2 days after irradiation. Urine
samples were used to determine the 8-OHdG level using an enzyme-linked
immunosorbent assay and the creatinine level by a modified Jaffe reaction. For
long-term effects, rats at Day 17 of pregnancy were fed a diet containing
curcumin for 3 days before and/or 3 days after irradiation with 1.5 Gy, and
received a pellet of diethylstilbestrol as the promoter. The rats were examined
for mammary and pituitary tumors for 1 year. To determine survival, virgin rats
received whole-body irradiation with 9.6 Gy and were fed a diet containing
curcumin for 3 days before and/or 3 days after irradiation. After irradiation,
all rats were assessed daily for survival for 30 days. RESULTS: Acutely in
virgin rats irradiated with 3 Gy, the creatinine-corrected concentration and
total amount of 8-OHdG in the 24-h urine samples were higher (approximately
1.3-fold) than the corresponding values in the nonirradiated controls. Adding
curcumin to the diet for 3 days before and/or 2 days after irradiation reduced
the elevated 8-OHdG levels by 50-70%. The evaluation of the protective action of
curcumin against the long-term effects revealed that curcumin significantly
decreased the incidence of mammary and pituitary tumors. However, the
experiments on survival revealed that curcumin was not effective when
administered for 3 days before and/or 3 days after irradiation (9.6 Gy).
CONCLUSION: These findings demonstrate that curcumin can be used as an effective
radioprotective agent to inhibit acute and chronic effects, but not mortality,
after irradiation.

PMID: 12062620 [PubMed - indexed for MEDLINE]

187: J Immunol. 2002 Jun 15;168(12):6506-13.

Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12
signaling through Janus kinase-STAT pathway in T lymphocytes.

Natarajan C, Bright JJ.

Division of Neuroimmunology, Department of Neurology, Vanderbilt University
Medical Center, Nashville, TN 37212, USA.

Experimental allergic encephalomyelitis (EAE) is a CD4(+) Th1 cell-mediated
inflammatory demyelinating autoimmune disease of the CNS that serves as an
animal model for multiple sclerosis (MS). IL-12 is a proinflammatory cytokine
that plays a crucial role in the induction of neural Ag-specific Th1
differentiation and pathogenesis of CNS demyelination in EAE and MS. Curcumin
(1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a naturally
occurring polyphenolic phytochemical isolated from the rhizome of the medicinal
plant Curcuma longa. It has profound anti-inflammatory activity and been
traditionally used to treat inflammatory disorders. In this study we have
examined the effect and mechanism of action of curcumin on the pathogenesis of
CNS demyelination in EAE. In vivo treatment of SJL/J mice with curcumin
significantly reduced the duration and clinical severity of active immunization
and adoptive transfer EAE. Curcumin inhibited EAE in association with a decrease
in IL-12 production from macrophage/microglial cells and differentiation of
neural Ag-specific Th1 cells. In vitro treatment of activated T cells with
curcumin inhibited IL-12-induced tyrosine phosphorylation of Janus kinase 2,
tyrosine kinase 2, and STAT3 and STAT4 transcription factors. The inhibition of
Janus kinase-STAT pathway by curcumin resulted in a decrease in IL-12-induced T
cell proliferation and Th1 differentiation. These findings highlight the fact
that curcumin inhibits EAE by blocking IL-12 signaling in T cells and suggest
its use in the treatment of MS and other Th1 cell-mediated inflammatory
diseases.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12055272 [PubMed - indexed for MEDLINE]

188: Int J Mol Med. 2002 May;9(5):481-4.

Selective induction of apoptosis by ar-turmerone isolated from turmeric (Curcuma
longa L) in two human leukemia cell lines, but not in human stomach cancer cell
line.

Aratanechemuge Y, Komiya T, Moteki H, Katsuzaki H, Imai K, Hibasami H.

Faculty of Bioresources, Mie University, Tsu-city, Mie 514-0001, Japan.

We have investigated the effects of ar-turmerone isolated from turmeric (Curcuma
longa L) on DNA of human leukemia cell lines, Molt 4B, HL-60 and stomach cancer
KATO III cells. It was found that selective induction of apoptosis by
ar-turmerone was observed in human leukemia Molt 4B and HL-60 cells, but not in
human stomach cancer KATO III cells. Morphological changes showing apoptotic
bodies were observed in the human HL-60 and Molt 4B cells treated with
ar-turmerone. The fragmentation of DNA by ar-turmerone to oligonucleosomal-sized
fragments that is a characteristic of apoptosis was observed to be
concentration- and time-dependent in Molt 4B and HL-60 cells, but not in KATO
III cells. The data of the present study show that the suppression by
ar-turmerone of growth of these leukemia cell lines results from the induction
of apoptosis by this compound.

PMID: 11956652 [PubMed - indexed for MEDLINE]

189: J Econ Entomol. 2002 Feb;95(1):183-9.

Bioactivities of the leaf essential oil of Curcuma longa (var. ch-66) on three
species of stored-product beetles (Coleoptera).

Tripathi AK, Prajapati V, Verma N, Bahl JR, Bansal RP, Khanuja SP, Kumar S.

Central Institute of Medicinal and Aromatic Plants, Lucknow, India.

Essential oil extracted from the leaves of turmeric, Curcuma longa L., was
investigated for contact and fumigant toxicity and its effect on progeny
production in three stored-product beetles, Rhyzopertha dominica F. (lesser
grain borer), Sitophilus oryzae L. (rice weevil), and Tribolium castaneum Herbst
(red flour beetle). Oviposition-deterrent and ovicidal actions of C. longa leaf
oil were also evaluated against T. castaneum. The oil was insecticidal in both
contact and fumigant toxicity assays. The adults of R. dominica were highly
susceptible to contact action of C. longa leaf oil, with LD50 value of 36.71
microg/mg weight of insect, whereas in the fumigant assay, adults of S. oryzae
were highly susceptible with LC50 value of 11.36 mg/liter air. Further, in T.
castaneum, the C. longa oil reduced oviposition and egg hatching by 72 and 80%,
respectively at the concentration of 5.2 mg/cm2. At the concentration of 40.5
mg/g food, the oil totally suppressed progeny production of all the three test
insects. Nutritional indices indicate >81% antifeedant action of the oil against
R. dominica, S. oryzae and T castaneum at the highest concentration tested.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11942755 [PubMed - indexed for MEDLINE]

190: Se Pu. 1998 Nov;16(6):528-9.

[Determination of chemical constituents of the volatile oil from Curcuma longa
by gas chromatography-mass spectrometry]

[Article in Chinese]

Hu Y, Du Q, Tang Q.

175th Hospital PLA, Zhangzhou, 363000.

The study of chemical constituents of the volatile oil from Curcuma longa is
reported. The volatile oil was extracted by steam distillation. Fifteen
components in the oil were separated and identified by gas chromatography-mass
spectrometry(GC/MS). The results were elucidated based on the NBS standard mass
spectral data. The total ion current chromatogram showed their mass fraction by
normalization method. alpha-curcumene, alpha-zingiberene, 1,8-cineole and
zerumbone, which had been reported before were found in Curcuma longa volatile
oil, but 1-(3-cyclopentylpropyl)-2,4-dimethylbenzene, beta-sesquiphellandrene,
germacrene etc identified simultaneously in the oil had never been reported. The
major chemical constituent of the volatile oil from Curcuma longa is
alpha-curcumene.

Publication Types:
English Abstract

PMID: 11938917 [PubMed - indexed for MEDLINE]

191: Phytother Res. 2002 Mar;16(2):171-3.

Effect of curcumin on ethanol-induced stress on mononuclear cells.

Rajakrishnan V, Shiney SJ, Sudhakaran PR, Menon VP.

Department of Biochemistry, Annamalai University, Annamalainagar--608 002, Tamil
Nadu, India.

Blood cells in circulation are exposed to a wide variety of stress-causing
agents, causing a number of changes including interactions with other cells and
the extracellular matrix of the endothelial wall. In order to understand the
role of curcumin, an antioxidant principle from Curcuma longa Linn., on blood
mononuclear cells from rabbits given ethanol for 30 days and ethanol with
curcumin, cells were isolated and an attachment assay was carried out. The
monocytes from ethanol-treated rabbits showed a lesser attachment to collagen,
the major component of the vessel wall subendothelium, and those from curcumin
treated animals along with ethanol showed a higher affinity to collagen, causing
an alteration in the attachment of monocyte to collagen due to ethanol-induced
stress. Copyright 2002 John Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11933122 [PubMed - indexed for MEDLINE]

192: Public Health Nutr. 2001 Dec;4(6A):1385-8.

Nutrition and ageing.

Miquel J.

Department of Biotechnology, University of Alicante, Denia, Spain.
[email protected]

The reviewed literature indicates that, even in industrialised countries, the
nutrition of mature and aged subjects is often inadequate (because of deficiency
or excess), which may lead to premature or pathological senescence. Recent
nutritional research on ageing laboratory animals shows that dietary restriction
may be the most effective procedure to achieve a long and disease-free life
span, probably owing to a better protection against mitochondria-linked oxygen
stress. Likewise, the experimental and clinical work from many laboratories,
including our own, indicates that age-dependent changes in the cardiovascular
and immune systems are linked to oxygen stress and that an adequate intake of
dietary antioxidants may protect those systems against chronic degenerative
syndromes in the physiopathology of which reactive oxygen species (ROS) play a
key role. The extant data indicate that the antioxidant vitamins C and E are
centrally involved in defending the above two systems against ROS attack.
Moreover, recent research suggests that the glutathione-related thiolic
antioxidants, thiazolidine carboxylic acid (thioproline) and N-acetylcysteine,
as well as the phenolic liposoluble 'co-antioxidants' of Curcuma longa, may have
a significant protective effect against age-related atherogenesis and immune
dysfunction. Key messages from this paper are the following. (1) It is generally
accepted that oxygen free radicals released in metabolic reactions play a key
role in the physiopathology of 'normal ageing' and of many age-related
degenerative diseases. (2) Consumption of adequate levels of antioxidants in the
diet is essential in order to preserve health in old age. (3) A certain degree
of protection against atherogenesis and immune dysfunction may be achieved by
preventing vitamin E deficiency and an excessive oxidation of the
glutathione-supported thiol pool.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 11918486 [PubMed - indexed for MEDLINE]

193: Biol Pharm Bull. 2002 Mar;25(3):386-9.

Latent activity of curcumin against leishmaniasis in vitro.

Saleheen D, Ali SA, Ashfaq K, Siddiqui AA, Agha A, Yasinzai MM.

Department of Biochemistry, The Aga Khan University, Karachi, Pakistan.

In this study the anti-proliferative effect of curcumin (curcuma longa) that is
the active ingredient of ground dried rhizome has been studied against three
local and three reference leishmanial strains, Leishmania major, Leishmania
tropica and Leishmania infantum (Pakistani isolate). Curcumin has shown an
average IC50 of 5.3 microM against promastigotes of various leishmanial strains
which is much lower as compared with pentamidine that is one of the basic
treatments against leishmaniasis. The main draw back attributed to these assays
performed on promastigotes is the heterogeneity of results compared with those
obtained with intracellular amastigotes or with in vivo effect. We also tested
activity of curcumin against axenic amastigote like cells (AALC) of L. major
strain (MHOM/PK/88/DESTO). Curcumin proves to be far more potent then
pentamidine against AALC which further strengthens the fact about its
leishmaniacidal activity.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11913540 [PubMed - indexed for MEDLINE]

194: Mutat Res. 2002 Mar 25;515(1-2):197-202.

Antimutagenic potential of curcumin on chromosomal aberrations in Wistar rats.

Shukla Y, Arora A, Taneja P.

Environmental Carcinogenesis Division, Industrial Toxicology research Centre,
P.O. Box 80, M.G. Marg, UP 226001, Lucknow, India. [email protected]

Curcumin, a yellow pigment commonly used as a spice and food coloring agent is
obtained from rhizomes of Curcuma longa and is a major chemopreventive component
of turmeric. In the present set of investigations the antimutagenic potential of
curcumin has been evaluated using in vivo chromosomal aberration assay in Wistar
rats. Cyclophosphamide (CP), a well-known mutagen was given by intraperitoneal
(i.p.) injection at the dose of 40 mg/kg body weight (b.w.). Curcumin was given
at the dose of 100 and 200 mg/kg b.w. through gastric intubation for seven
consecutive days prior to CP treatment. The animals were sacrificed at the
sampling time of 24 h after treatment and their bone marrow tissue was analyzed
for chromosomal damage and mitotic index. In CP treated animals a significant
induction of chromosomal aberration was recorded with decrease in mitotic index.
However, in curcumin-supplemented animals, no significant induction in
chromosomal damage or change in mitotic index was recorded. In different
curcumin-supplemented groups, a dose dependent significant decrease in CP
induced clastogenicity was recorded. The incidence of aberrant cells was found
to be reduced by both the doses of curcumin when compared to CP treated group.
The anticytotoxic potential of curcumin towards CP was also evident as the
status of mitotic index was found to show increment. The study revealed the
antigenotoxic potential of curcumin against CP induced chromosomal mutations.

PMID: 11909768 [PubMed - indexed for MEDLINE]

195: Plant Foods Hum Nutr. 2002 Winter;57(1):41-52.

Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats.

Arun N, Nalini N.

Department of Biochemistry, Annamalai University, Annamalainagar, Tamil Nadu,
India.

In the traditional system of medicine, Ayurveda, several spices and herbs are
thought to possess medicinal properties. Among the spices, turmeric rhizomes
(Curcuma longa. Linn.) are used as flavoring and coloring agents in the Indian
diet everyday. In this research, we studied the effect of turmeric and its
active principle, curcumin, on diabetes mellitus in a rat model. Alloxan was
used to induce diabetes. Administration of turmeric or curcumin to diabetic rats
reduced the blood sugar, Hb and glycosylated hemoglobin levels significantly.
Turmeric and curcumin supplementation also reduced the oxidative stress
encountered by the diabetic rats. This was demonstrated by the lower levels of
TBARS (thiobarbituric acid reactive substances), which may have been due to the
decreased influx of glucose into the polyol pathway leading to an increased
NADPH/NADP ratio and elevated activity of the potent antioxdiant enzyme GPx.
Moreover, the activity of SDH (sorbitol dehydrogenase), which catalyzes the
conversion of sorbitol to fructose, was lowered significantly on treatment with
turmeric or curcumin. These results also appeared to reveal that curcumin was
more effective in attenuating diabetes mellitus related changes than turmeric.

PMID: 11855620 [PubMed - indexed for MEDLINE]

196: Cell Stress Chaperones. 2001 Oct;6(4):368-76.

Induction of stress response renders human tumor cell lines resistant to
curcumin-mediated apoptosis: role of reactive oxygen intermediates.

Khar A, Ali AM, Pardhasaradhi BV, Varalakshmi CH, Anjum R, Kumari AL.

Centre for Cellular and Molecular Biology, Hyderabad, India. [email protected]

Curcumin, a well-known dietary pigment derived from Curcuma longa, has been
shown to be a potent antiinflammatory, antioxidant, and anticarcinogenic
compound. The present study was designed to investigate the cytotoxic potential
of curcumin against a range of human tumor cell lines in an attempt to
understand its mechanism of action, which may lead to its possible therapeutic
applications. We have shown that different cancer cell lines differ in their
sensitivity to curcumin. Cell lines established from malignancies like leukemia,
breast, colon, hepatocellular, and ovarian carcinomas underwent apoptosis in the
presence of curcumin, whereas cell lines from lung, kidney, prostate, cervix,
CNS malignancies, and melanomas showed resistance to the cytotoxic effects of
curcumin. Sensitivity of the cancer cell lines to curcumin correlated with the
generation of superoxide radicals as determined by the reduction of
ferricytochrome C. Curcumin-resistant tumor cell lines showed significantly
higher production of Hsp70, thus mounting a stress response and protecting the
cells from the apoptotic cell death. These observations yield clues toward
understanding the regulation of the cell death machinery by the stress proteins.
Interestingly, curcumin had no effect on nontransformed cell lines, which showed
neither superoxide generation nor the induction of a stress response. These
observations demonstrate that curcumin is an interesting molecule with varied
actions, depending on the cell type.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 11795474 [PubMed - indexed for MEDLINE]

197: Fresenius J Anal Chem. 2001 Dec;371(7):1009-17.

Non-destructive NIR-FT-Raman analyses in practice. Part I. Analyses of plants
and historic textiles.

Andreev GN, Schrader B, Schulz H, Fuchs R, Popov S, Handjieva N.

Department of Chemistry, University of Plovdiv, Bulgaria.

Non-destructive analysis of natural substances in plants as well as of old dyed
textiles by Raman spectroscopy has not been possible using conventional
techniques. Exciting lines from the visible part of the spectrum produced
photochemical and thermal decomposition of the objects as well as strong
fluorescence. Using Nd:YAG laser excitation at 1,064 nm together with a special
sample arrangement and interferometric recording, various polyacetylenes in
Aethusa cynapium and in chamomile (Chamomilla recutita) and the main valuable
substances in gentian species (Gentiana lutea and G. punctata), curcuma roots
(Curcuma longa), cinnamon (Cinnamomum zeylanicum), fennel (Foeniculum vulgare),
clove (Caryophyllus aromaticus), and ginger (Zingiber officinale) were analyzed
non-destructively and discussed in comparison with the corresponding pure
standard compounds. We further analyzed non-destructively the FT Raman spectra
of collections of historical textiles and lakes used for dyeing. It is possible
to distinguish the main dye component non-destructively by using Raman bands.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11769790 [PubMed - indexed for MEDLINE]

198: Carcinogenesis. 2002 Jan;23(1):143-50.

Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8,
BID cleavage and cytochrome c release: its suppression by ectopic expression of
Bcl-2 and Bcl-xl.

Anto RJ, Mukhopadhyay A, Denning K, Aggarwal BB.

Cytokine Research Section, Department of Bioimmunotherapy, Box 143, The
University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston,
TX 77030, USA.

Pharmacologically safe compounds that can inhibit the proliferation of tumor
cells have potential as anticancer agents. Curcumin, a diferuloylmethane, is a
major active component of the food flavor turmeric (Curcuma longa) that has been
shown to inhibit the proliferation of a wide variety of tumor cells. The
apoptotic intermediates through which curcumin exhibits its cytotoxic effects
against tumor cells are not known, and the participation of antiapoptotic
proteins Bcl-2 or Bcl-xl in the curcumin-induced apoptosis pathway is not
established. In the present report we investigated the effect of curcumin on the
activation of the apoptotic pathway in human acute myelogenous leukemia HL-60
cells and in established stable cell lines expressing Bcl-2 and Bcl-xl. Curcumin
inhibited the growth of HL-60 cells (neo) in a dose- and time-dependent manner,
whereas Bcl-2 and Bcl-xl-transfected cells were relatively resistant. Curcumin
activated caspase-8 and caspase-3 in HL-60 neo cells but not in Bcl-2 and
Bcl-xl-transfected cells. Similarly, time-dependent poly(ADP)ribose polymerase
(PARP) cleavage by curcumin was observed in neo cells but not in Bcl-2 and
Bcl-xl-transfected cells. Curcumin treatment also induced BID cleavage and
mitochondrial cytochrome c release in neo cells but not in Bcl-2 and
Bcl-xl-transfected cells. In neo HL-60 cells, curcumin also downregulated the
expression of cyclooxygenase-2. Because DN-FLICE blocked curcumin-induced
apoptosis, caspase-8 must play a critical role. Overall, our results indicate
that curcumin induces apoptosis through mitochondrial pathway involving
caspase-8, BID cleavage, cytochrome c release, and caspase-3 activation. Our
results also suggest that Bcl-2 and Bcl-xl are critical negative regulators of
curcumin-induced apoptosis.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11756235 [PubMed - indexed for MEDLINE]

199: Phytother Res. 2001 Nov;15(7):618-20.

Evaluation of Ophthacare eye drops--a herbal formulation in the management of
various ophthalmic disorders.

Biswas NR, Gupta SK, Das GK, Kumar N, Mongre PK, Haldar D, Beri S.

All India Institute of Medical Sciences, New Delhi 110029, India.

An open prospective multicentre clinical trial was conducted in patients
suffering from various ophthalmic disorders namely, conjunctivitis, conjunctival
xerosis (dry eye), acute dacryocystitis, degenerative conditions (pterygium or
pinguecula) and postoperative cataract patients with a herbal eye drop
preparation (Ophthacare) containing basic principles of different herbs which
have been conventionally used in the Ayurvedic system of medicine since time
immemorial. These include Carum copticum, Terminalia belirica, Emblica
officinalis, Curcuma longa, Ocimum sanctum, Cinnamomum camphora, Rosa damascena
and meldespumapum. These herbs reportedly possess antiinfective and
antiinflammatory properties. The present study was undertaken to elucidate the
role of this herbal product in a variety of eye ailments. Side effects, if any,
were noted during the study. An improvement was observed with the treatment of
the herbal eye drop treatment in most cases. There were no side effects observed
during the course of the study and the eye drop was well tolerated by the
patients. The herbal eye drop Ophthacare has a useful role in a variety of
infective, inflammatory and degenerative ophthalmic disorders. Copyright 2001
John Wiley & Sons, Ltd.

Publication Types:
Clinical Trial
Multicenter Study

PMID: 11746845 [PubMed - indexed for MEDLINE]

200: Planta Med. 2001 Dec;67(9):876-7.

Diarylheptanoids with free radical scavenging and hepatoprotective activity in
vitro from Curcuma longa.

Song EK, Cho H, Kim JS, Kim NY, An NH, Kim JA, Lee SH, Kim YC.

Assay-guided fractionation of the EtOAc soluble fraction of the rhizomes of
Curcuma longa furnished three DPPH free radical scavenging diarylheptanoids,
curcumin (1), demethoxycurcumin (2), and bisdemethoxycurcumin (3). Compounds 1-3
showed the DPPH radical scavenging effects with IC(50) values of 2.8, 39.2,
308.7 microM, respectively. L-Ascorbic acid and resveratrol as positive controls
exhibited IC(50) values of 22.5 and 25.0 microM, respectively. Compounds 1-3
showed significant hepatoprotective effects on tacrine-induced cytotoxicity in
human liver-derived Hep G2 cells. The EC(50) values of 1-3 are 86.9, 70.7, and
50.2 microM, respectively. Silybin (EC(50) = 69.0 microM) and silychristin
(EC(50) = 82.7 microM) were used as positive controls.

Publication Types:
Letter
Research Support, Non-U.S. Gov't

PMID: 11745031 [PubMed - indexed for MEDLINE]

201: Anticancer Res. 2001 Jul-Aug;21(4B):2895-900.

Phase I clinical trial of curcumin, a chemopreventive agent, in patients with
high-risk or pre-malignant lesions.

Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR,
Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH,
Wang YJ, Tsai CC, Hsieh CY.

Department of Internal Medicine, National Taiwan University College of Medicine,
Taipei. [email protected]

Curcumin (diferuloylmethane), a yellow substance from the root of the plant
Curcuma longa Linn., has been demonstrated to inhibit carcinogenesis of murine
skin, stomach, intestine and liver. However, the toxicology, pharmacokinetics
and biologically effective dose of curcumin in humans have not been reported.
This prospective phase-I study evaluated these issues of curcumin in patients
with one of the following five high-risk conditions: 1) recently resected
urinary bladder cancer; 2) arsenic Bowen's disease of the skin; 3) uterine
cervical intraepithelial neoplasm (CIN); 4) oral leucoplakia; and 5) intestinal
metaplasia of the stomach. Curcumin was taken orally for 3 months. Biopsy of the
lesion sites was done immediately before and 3 months after starting curcumin
treament. The starting dose was 500 mg/day. If no toxicity > or = grade II was
noted in at least 3 successive patients, the dose was then escalated to another
level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. The
concentration of curcumin in serum and urine was determined by high pressure
liquid chromatography (HPLC). A total of 25 patients were enrolled in this
study. There was no treatment-related toxicity up to 8,000 mg/day. Beyond 8,000
mg/day, the bulky volume of the drug was unacceptable to the patients. The serum
concentration of curcumin usually peaked at 1 to 2 hours after oral intake of
crucumin and gradually declined within 12 hours. The average peak serum
concentrations after taking 4,000 mg, 6,000 mg and 8,000 mg of curcumin were
0.51 +/- 0.11 microM, 0.63 +/- 0.06 microM and 1.77 +/- 1.87 microM,
respectively. Urinary excretion of curcumin was undetectable. One of 4 patients
with CIN and 1 of 7 patients with oral leucoplakia proceeded to develop frank
malignancies in spite of curcumin treatment. In contrast, histologic improvement
of precancerous lesions was seen in 1 out of 2 patients with recently resected
bladder cancer, 2 out of 7 patients of oral leucoplakia, 1 out of 6 patients of
intestinal metaplasia of the stomach, I out of 4 patients with CIN and 2 out of
6 patients with Bowen's disease. In conclusion, this study demonstrated that
curcumin is not toxic to humans up to 8,000 mg/day when taken by mouth for 3
months. Our results also suggest a biologic effect of curcumin in the
chemoprevention of cancer.

Publication Types:
Clinical Trial
Clinical Trial, Phase I
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 11712783 [PubMed - indexed for MEDLINE]

202: Crit Care Med. 2001 Nov;29(11):2199-204.

Comment in:
Crit Care Med. 2001 Nov;29(11):2231-2.

Curcumin, a medicinal herbal compound capable of inducing the heat shock
response.

Dunsmore KE, Chen PG, Wong HR.

Division of Critical Care Medicine, Children's Hospital Medical Center and
Children's Hospital Research Foundation. Cincinnati, OH 45229, USA.

OBJECTIVE: There is interest in developing pharmacologic inducers of the heat
shock response as a means to confer cytoprotection in the clinical setting. We
propose that a potential strategy for screening novel pharmacologic inducers of
the heat shock response is to examine known inhibitors of the transcription
factor nuclear factor-kappaB. Curcumin, derived from the tropical herb Curcuma
longa, is a recently described inhibitor of nuclear factor-kappaB and is widely
used in Eastern medicinal practices. We tested the hypothesis that curcumin can
induce expression of heat shock protein 70. DESIGN: Experimental. SETTING:
University laboratory. SUBJECTS: HeLa cells. INTERVENTIONS: HeLa cells were
exposed to varying concentrations of curcumin and analyzed for expression of
heat shock protein 70 by Western blot. MEASUREMENTS AND MAIN RESULTS: Activation
of the transcription factor, heat shock factor-1, was analyzed by
electromobility shift assays. Curcumin-mediated inhibition of nuclear
factor-kappaB activation was measured by transiently transfecting cells with a
nuclear factor-kappaB luciferase reporter plasmid. The role of heat shock
factor-1 in curcumin-mediated expression of heat shock protein 70 was tested in
embryonic fibroblasts derived from heat shock factor-1 knockout mice. Induction
of the heat shock response was quantified by transiently transfecting cells with
a heat shock protein 70 promoter-luciferase reporter plasmid. Cell viability was
measured by using the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
tetrazolium bromide assay. Curcumin induced expression of heat shock protein 70,
the major inducible heat shock protein in cells undergoing the heat shock
response, in a dose-dependent and time-dependent manner. Curcumin induced
specific nuclear translocation and activation of heat shock factor-1.
Curcumin-mediated expression of heat shock protein 70 was reduced substantially
in fibroblasts having genetic ablation of heat shock factor-1. The extent of
induction of the heat shock response correlated, in part, with cellular
toxicity. CONCLUSIONS: Curcumin, a widely used medicinal compound, induces the
heat shock response in vitro as measured by expression of heat shock protein 70.
The mechanism of heat shock protein 70 induction depends on activation of heat
shock factor-1. Examining known inhibitors of nuclear factor-kappaB for their
ability to induce heat shock protein 70 may be a valid screening method to
discover novel pharmacologic inducers of the heat shock response.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

PMID: 11700423 [PubMed - indexed for MEDLINE]

203: Differentiation. 2001 Sep;68(2-3):133-40.

Curcumin-induced differentiation of mouse embryonal carcinoma PCC4 cells.

Batth BK, Tripathi R, Srinivas UK.

Centre for Cellular and Molecular Biology, Hyderabad, India.

Curcumin, a natural component of turmeric extracted from the rhizomes of Curcuma
longa, is known to exhibit a number of biological properties. In the present
study, curcumin, at low concentration, was shown to induce differentiation in
embryonal carcinoma cell line PCC4. In response to curcumin, PCC4 cells ceased
to proliferate and showed cell cycle arrest at G1 phase after 4 hours of
treatment, followed by their differentiation which is characterized by increase
of nuclear/cytoplasmic ratio. The expression of hsp 70 was also seen upon 8 h of
curcumin treatment, and it remained constant up to 48 h. Differentiated cells
also expressed a series of differentiation markers such as lamin A,
well-established actin, and keratin cytoskeleton. We used mRNA differential
display analysis to identify the genes that are regulated during
curcumin-induced differentiation of PCC4 cells. We cloned and sequenced three
partial cDNAs that were differentially expressed in normal and differentiated
cells. Sequence comparison of one downregulated cDNA (Al) has shown homology to
a gene present on mouse chromosome five, while the two upregulated cDNA (C1 and
C7) are homologous to several mouse ESTs clones from organs of mesodermal
origin. We have identified the full-length coding sequence of the Cl fragment
with a putative amino acid sequence. Tissue-specific Northern with RNA from
adult mouse organs with the C1 fragment alone showed hybridization with mRNA
from several tissues, whereas the same Northern with only the coding sequence
showed expression of C1 gene mainly in the adult kidney. Homology search
revealed that C1 sequence is part of the 3' UTR and may be common to several
genes expressed in many tissues. Thus, curcumin appears to differentiate
embryonal carcinoma cell PCC4, and one of the upregulated genes seems to be
expressed mainly in the adult kidney.

PMID: 11686235 [PubMed - indexed for MEDLINE]

204: Biochem Biophys Res Commun. 2001 Nov 2;288(3):658-65.

Mechanisms of curcumin-induced apoptosis of Ehrlich's ascites carcinoma cells.

Pal S, Choudhuri T, Chattopadhyay S, Bhattacharya A, Datta GK, Das T, Sa G.

Animal Physiology Section, Bose Institute, Kolkata, 700 054, India.

Curcumin, the active ingredient from the spice turmeric (Curcuma longa Linn), is
a potent antioxidant and anti-inflammatory agent. It has been recently
demonstrated to possess discrete chemopreventive activities. However, the
molecular mechanisms underlying such anticancer properties of curcumin still
remain unrealized, although it has been postulated that induction of apoptosis
in cancer cells might be a probable explanation. In the current study, curcumin
was found to decrease the Ehrlich's ascites carcinoma (EAC) cell number by the
induction of apoptosis in the tumor cells as evident from flow-cytometric
analysis of cell cycle phase distribution of nuclear DNA and oligonucleosomal
fragmentation. Probing further into the molecular signals leading to apoptosis
of EAC cells, we observed that curcumin is causing tumor cell death by the
up-regulation of the proto-oncoprotein Bax, release of cytochrome c from the
mitochondria, and activation of caspase-3. The status of Bcl-2 remains unchanged
in EAC, which would signify that curcumin is bypassing the Bcl-2 checkpoint and
overriding its protective effect on apoptosis. Copyright 2001 Academic Press.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11676493 [PubMed - indexed for MEDLINE]

205: Chin Med J (Engl). 1999 Apr;112(4):308-11.

Effects of Curcuma Longa on proliferation of cultured bovine smooth muscle cells
and on expression of low density lipoprotein receptor in cells.

Zhang W, Liu D, Wo X, Zhang Y, Jin M, Ding Z.

Department of Biochemistry, Shanxi Medical University, Taiyuan 030001, China.

OBJECTIVE: To investigate the inhibitory effects of aqueous turmeric extract
(AqT) and serum of rats orally treated with ethanol extract of turmeric (SeT) on
proliferation of vascular smooth muscle cells (VSMC) and its effects on the
expression of low density lipoprotein receptor (LDL-R) antigen on the surface of
smooth muscle cells. METHODS: Enzyme-linked immunosorbent assay (ELISA) for the
expression of LDL-R protein and thiazolyl blue (MTT) assay for the proliferation
of VSMC were used in this study. RESULTS: Both aqueous turmeric extract (AqT)
and serum of rats orally treated with ethanol extract of turmeric (SeT) could
inhibit 10% serum activated proliferation of VSMC. The inhibition shown in both
experiments was dose-dependent with an inhibitory rate of 18.9% at 20 mg/ml AqT
and rate of 20.1% at 10% SeT respectively. AqT up-regulated the expression of
LDL-R protein with a highest rate at 5 mg/ml AqT in 3% lipoprotein deficient
serum (LPDS). SeT did not show significant effect on the expression of LDL-R on
the surface of VSMC. CONCLUSION: The extracts of turmeric may be extended to
decrease the risk of atherosclerosis (AS).

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11593527 [PubMed - indexed for MEDLINE]

206: Altern Med Rev. 2001 Sep;6 Suppl:S62-6.

Curcuma longa (turmeric). Monograph.

[No authors listed]

Curcuma longa, a perennial herb, is a member of the Zingiberaceae (ginger)
family. The plant grows to a height of three to five feet, and is cultivated
extensively in Asia, India, China, and other countries with a tropical climate.
It has oblong, pointed leaves and bears funnel-shaped yellow flowers. The
rhizome is the portion of the plant used medicinally; it is usually boiled,
cleaned, and dried, yielding a yellow powder. Dried Curcuma longa is the source
of the spice turmeric, the ingredient that gives curry powder its characteristic
yellow color. Turmeric is used extensively in foods for both its flavor and
color. Turmeric has a long tradition of use in the Chinese and Ayurvedic systems
of medicine, particularly as an anti-inflammatory agent, and for the treatment
of flatulence, jaundice, menstrual difficulties, hematuria, hemorrhage, and
colic. Turmeric can also be applied topically in poultices to relieve pain and
inflammation. Current research has focused on turmeric's antioxidant,
hepatoprotective, anti-inflammatory, anticarcinogenic, and antimicrobial
properties, in addition to its use in cardiovascular disease and
gastrointestinal disorders.

PMID: 11591174 [PubMed - indexed for MEDLINE]

207: Bioorg Med Chem Lett. 2001 Sep 17;11(18):2541-3.

Total synthesis of Calebin-A, preparation of its analogues, and their neuronal
cell protectivity against beta-amyloid insult.

Kim DS, Kim JY.

The Program for Collaborative Research in Pharmaceutical Science and the
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy,
University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612,
USA. [email protected]

A total synthesis of Calebin-A (1), a novel curcuminoid isolated from turmeric
(Curcuma longa, Zingiberaceae) that has been demonstrated to protect neuronal
cells from beta-amyloid insult, was successfully achieved in four steps.
Elaborating on this synthetic route, 13 analogues were prepared for a
structure-activity relationship (SAR) study. It was found that the parent
compound 1 and derivatives 21, 28, and 30 protect PC12 rat pheocromocytoma and
IMR-32 human neuroblastoma cells from beta-amyloid(25-35) insult. These results
suggest that hydroxy group at para-position is most critical for the expression
of biological activity.

PMID: 11549465 [PubMed - indexed for MEDLINE]

208: Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho Hokoku. 2000;(118):71-6.

[Study on the characterizations of genus Curcuma plants on the strains of C.
longa L. and C. aromatica Salisb preserved at Izu station of NIHS]

[Article in Japanese]

Iida O, Kohjyouma M, Katsuki S, Sakamoto S, Maitani T, Watanabe T.

[email protected]

To clarify the characteristics of genus Curcuma plants, we studied the
properties of six strains of Curcuma longa L. and two strains of C. aromatica
Salisb. preserved at Izu Experimental Station for Medicinal Plants of National
Institute of Health Sciences. Six strains of C. longa were classified into three
types according to morphological characteristics, rhizome production, and
differences in curcuminoid content of rhizome. The curcuminoid content of the
rhizomes in each strain ranged from 2.20 mg/g to 55.23 mg/g. Strains showing a
high curcuminoid content had a low rhizome yield. No difference was observed
between two strains of C. aromatica in terms of morphological characteristics.
C. longa can be easily distinguished by differences in the development of
tuberous roots and the color of the rhizome cross section.

Publication Types:
English Abstract

PMID: 11534130 [PubMed - indexed for MEDLINE]

209: Free Radic Biol Med. 2001 Sep 1;31(5):670-8.

Effect of glutathione depletion on caspase-3 independent apoptosis pathway
induced by curcumin in Jurkat cells.

Piwocka K, Jaruga E, Skierski J, Gradzka I, Sikora E.

Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental
Biology, Warsaw, Poland.

Curcumin, a yellow pigment from Curcuma longa, exhibits anti-inflammatory,
antitumor, and antioxidative properties. Although its precise mode of action has
not been elucidated so far, numerous studies have shown that curcumin may induce
apoptosis in normal and cancer cells. Previously, we showed that in Jurkat cells
curcumin induced nontypical apoptosis-like pathway, which was independent of
mitochondria and caspase-3. Now we show that the inhibition of caspase-3 by
curcumin, which is accompanied by attenuation of internucleosomal DNA
fragmentation, may be due to elevation of glutathione, which increased in
curcumin-treated cells to 130% of control. We have demonstrated that glutathione
depletion does not itself induce apoptosis in Jurkat cells; though, it can
release cytochrome c from mitochondria and caspase-3 from inhibition by
curcumin, as shown by Western blot. The level of Bcl-2 protein was not affected
by glutathione depletion even upon curcumin treatment. Altogether, our results
show that in Jurkat cells curcumin prevents glutathione decrease, thus
protecting cells against caspase-3 activation and oligonucleosomal DNA
fragmentation. On the other hand, it induces nonclassical apoptosis via a
still-unrecognized mechanism, which leads to chromatin degradation and
high-molecular-weight DNA fragmentation.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11522452 [PubMed - indexed for MEDLINE]

210: Planta Med. 2001 Aug;67(6):580-4.

Essential oil composition and antimicrobial activity of three Zingiberaceae from
S.Tome e Principe.

Martins AP, Salgueiro L, Goncalves MJ, da Cunha AP, Vila R, Canigueral S,
Mazzoni V, Tomi F, Casanova J.

The essential oil composition of three Zingiberaceae widely used as medicinal
aromatic plants from S. Tome and Principe: Aframomum danielli (Hook. f.) K.
Schum., Curcuma longa L. and Zingiber officinale Rosc. was studied. Two samples
of the essential oils from fruit of A. danielli and from rhizomes of the other
two species, were obtained by hydrodistillation and analyzed by GC, GC-MS, and
(13)C-NMR. The essential oil from fruits of A. danielli has been studied for the
first time and was characterised by its high content of monoterpenes, with
1,8-cineole (25.5 - 34.4 %) the major constituent, followed by beta-pinene (14.1
- 15.2 %) and alpha-terpineol (9.9 - 12.1 %). Essential oils from the rhizomes
of C. longa contained a lower content of ar-turmerone (4.0 - 12.8 %) than those
reported in the literature for C. longa from other origins (24.7 - 31.4 %),
whereas the results for Z. officinale essential oils were in accordance with the
literature data. The essential oils of A. danielli and Z. officinale showed
antimicrobial activity against all Gram-positive and Gram-negative bacteria
tested, as well as against yeasts and filamentous fungi, using the agar
diffusion method.

Publication Types:
Letter
Research Support, Non-U.S. Gov't

PMID: 11509990 [PubMed - indexed for MEDLINE]

211: Mutat Res. 2001 Sep 1;480-481:243-68.

Molecular mechanisms underlying chemopreventive activities of anti-inflammatory
phytochemicals: down-regulation of COX-2 and iNOS through suppression of
NF-kappa B activation.

Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK, Lee SS.

College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul
151-742, South Korea. [email protected]

A wide array of phenolic substances, particularly those present in edible and
medicinal plants, have been reported to possess substantial anticarcinogenic and
antimutagenic activities. The majority of naturally occurring phenolics retain
antioxidative and anti-inflammatory properties which appear to contribute to
their chemopreventive or chemoprotective activity. Cyclooxygenase-2 (COX-2)
inducible and nitric oxide synthase (iNOS) are important enzymes that mediate
inflammatory processes. Improper up-regulation of COX-2 and/or iNOS has been
associated with pathophysiology of certain types of human cancers as well as
inflammatory disorders. Since inflammation is closely linked to tumor promotion,
substances with potent anti-inflammatory activities are anticipated to exert
chemopreventive effects on carcinogenesis, particularly in the promotion stage.
Examples are curcumin, a yellow pigment of turmeric (Curcuma longa L.,
Zingiberaceae), the green tea polyphenol epigallocatechin gallate (EGCG), and
resveratrol from grapes (Vitis vinifera, Vitaceae) that strongly suppress tumor
promotion. Recent studies have demonstrated that eukaryotic transcription factor
nuclear factor-kappa B (NF-kappa B) is involved in regulation of COX-2 and iNOS
expression. Several chemopreventive phytochemicals have been shown to inhibit
COX-2 and iNOS expression by blocking improper NF-kappa B activation. Multiple
lines of compelling evidence indicate that extracellular-regulated protein
kinase and p38 mitogen-activated protein kinase are key elements of the
intracellular signaling cascades responsible for NF-kappa B activation in
response to a wide array of external stimuli. Curcumin, EGCG and resveratrol
have been shown to suppress activation of NF-kappa B. One of the plausible
mechanisms underlying inhibition of NF-kappa B activation by aforementioned
phytochemicals involves repression of degradation of the inhibitory unit I kappa
B alpha, which hampers subsequent nuclear translocation of the functionally
active subunit of NF-kappa B.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 11506818 [PubMed - indexed for MEDLINE]

212: Mem Inst Oswaldo Cruz. 2001 Jul;96(5):723-8.

Biological activities of Curcuma longa L.

Araujo CC, Leon LL.

Laboratorio de Biologia de Tripanosomatideos, Instituto Oswaldo Cruz-Fiocruz,
21045-900 Rio de Janeiro, RJ, Brasil. [email protected]

There are several data in the literature indicating a great variety of
pharmacological activities of Curcuma longa L. (Zingiberaceae), which exhibit
anti-inflammatory, anti-human immunodeficiency virus, anti-bacteria, antioxidant
effects and nematocidal activities. Curcumin is a major component in Curcuma
longa L., being responsible for its biological actions. Other extracts of this
plant has been showing potency too. In vitro, curcumin exhibits anti-parasitic,
antispasmodic, anti-inflammatory and gastrointestinal effects; and also inhibits
carcinogenesis and cancer growth. In vivo, there are experiments showing the
anti-parasitic, anti-inflammatory potency of curcumin and extracts of C. longa
L. by parenteral and oral application in animal models. In this present work we
make an overview of the pharmacological activities of C. longa L., showing its
importance.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 11500779 [PubMed - indexed for MEDLINE]

213: Southeast Asian J Trop Med Public Health. 2001 Mar;32(1):208-15.

Phase II clinical trial on effect of the long turmeric (Curcuma longa Linn) on
healing of peptic ulcer.

Prucksunand C, Indrasukhsri B, Leethochawalit M, Hungspreugs K.

Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol
University, Bangkok, Thailand.

The study examined patients who had symptoms indicating peptic ulcer. Forty-five
patients, 24 males and 21 females, aged between 16-60 years were included in the
study. Twenty-five patients, 18 males and 7 females, were endoscoped, their
ulcers located in the duodenal bulb and gastric (angulus). The ulcer sizes
varied between 0.5 to 1.5 cm in diameter. Capsule-filled turmeric was given
orally in the dose of 2 capsules (300 mg each) five times daily, one half to an
hour before meals, at 16.00 hours and at bedtime continuously. The result after
4 weeks of treatment showed that ulcers were absent in 48% or 12 cases (DU 9 and
GU 3). Eighteen cases (DU 13 and GU 5) had absence of ulcer after 8 weeks of
treatment. Nineteen cases (76%) (DU 14 and GU 5) did not have ulcers after 12
weeks of treatment. The rest, 20 cases were not found to have ulcers and some
were not endoscoped. They appeared to have erosions, gastritis and dyspepsia.
They received turmeric capsules for 4 weeks of treatment. The abdominal pain and
discomfort satisfactorily subsided in the first and second week. They could take
normal foods instead of soft meals. Blood chemistry and hematology of all 54
patients had no significant changes in hematological system, liver and renal
functions both before and after treatment.

Publication Types:
Clinical Trial
Clinical Trial, Phase II

PMID: 11485087 [PubMed - indexed for MEDLINE]

214: J Vector Ecol. 2001 Jun;26(1):76-82.

Repellency of volatile oils from plants against three mosquito vectors.

Tawatsin A, Wratten SD, Scott RR, Thavara U, Techadamrongsin Y.

National Institute of Health, Department of Medical Sciences, Ministry of Public
Health, 88/7 Tiwanon Rd., Nonthaburi 11000, Thailand.

Volatile oils extracted by steam distillation from four plant species (turmeric
(Curcuma longa), kaffir lime (Citrus hystrix), citronella grass (Cymbopogon
winterianus) and hairy basil (Ocimum americanum)), were evaluated in mosquito
cages and in a large room for their repellency effects against three mosquito
vectors, Aedes aegypti, Anopheles dirus and Culex quinquefasciatus. The oils
from turmeric, citronella grass and hairy basil, especially with the addition of
5% vanillin, repelled the three species under cage conditions for up to eight
hours. The oil from kaffir lime alone, as well as with 5% vanillin added, was
effective for up to three hours. With regard to the standard repellent, deet
alone provided protection for at least eight hours against Ae. aegypti and Cx.
quinquefasciatus, but for six hours against An. dirus. However, deet with the
addition of 5% vanillin gave protection against the three mosquito species for
at least eight hours. The results of large room evaluations confirmed the
responses for each repellent treatment obtained under cage conditions. This
study demonstrates the potential of volatile oils extracted from turmeric,
citronella grass and hairy basil as topical repellents against both day- and
night-biting mosquitoes. The three volatile oils can be formulated with vanillin
as mosquito repellents in various forms to replace deet
(N,N-diethyl-3-methylbenzamide), the most common chemical repellent currently
available.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11469188 [PubMed - indexed for MEDLINE]

215: Southeast Asian J Trop Med Public Health. 2000;31 Suppl 1:178-82.

Antifungal activity of Curcuma longa grown in Thailand.

Wuthi-udomlert M, Grisanapan W, Luanratana O, Caichompoo W.

Department of Microbiology, Faculty of Pharmacy, Mahidol University, Bangkok,
Thailand.

Curcuma longa Linn. or turmeric (Zingiberaceae) is a medicinal plant widely used
and cultivated in tropical regions. According to Thai traditional texts, fresh
and dried rhizomes are used as peptic ulcer treatment, carminatives, wound
treatment and anti-inflammatory agent. Using hydro distillation, 1.88% and 7.02%
(v/w) volatile oils were extracted from fresh and dried rhizomes, respectively,
and 6.95% (w/w)crude curcuminoids were extracted from dried rhizomes. Dried
powder was extracted with 95% ethanol and yielded 29.52% (w/w) crude ethanol
extract composed of curcumin (11.6%), demethoxycurcumin (10.32%) and
bisdemethoxycurcumin (10.77%). These extracts were tested for antifungal
activity by agar disc diffusion method against 29 clinical strains of
dermatophytes. It was found that crude ethanol extract exhibited an inhibition
zone range of 6.1 to 26.0 mm. There was no inhibition activity from crude
curcuminoids while curcumin, demethoxycurcumin and bisdemethoxycutcumin gave
different inhibition zone diameters ranging from 6.1 to 16.0 mm. Although
antifungal activity of undiluted freshly distilled oil and 18-month-old oil
revealed some differences, the inhibition zone diameters for both extracts
varied within 26.1 to 46.0 mm. With 200 mg/ml ketoconazole, the activities of
the standard agent were similar to the oil, both freshly distilled and
18-month-old, but were significantly different from those of curcuminoid
compounds and crude ethanol extracts (p < 0.01). Turmeric oil was also tested
for its minimum inhibitory concentration (MIC) by broth dilution method. The
MICs of freshly distilled and 18-month-old oils were 7.8 and 7.2 mg/ml
respectively.

PMID: 11414453 [PubMed - indexed for MEDLINE]

216: Cytobios. 2001;105(409):71-82.

In vitro propagation and rhizome formation in Curcuma longa Linn.

Sunitibala H, Damayanti M, Sharma GJ.

Department of Life Sciences, Manipur University, Imphal, India.

Turmeric (Curcuma longa Linn.) which is cultivated by underground rhizomes is a
slow propagating species. Multiplication and callus induction starting from the
rhizome buds and shoot tips of C. longa in MS medium was carried out. A
combination of naphthalene acetic acid (NAA; 1.0 mg/l) with kinetin (Kn; 1.0
mg/l) or NAA (1.0 mg/l) with 6-benzylaminopurine (BAP; 2.0 mg/l) was optimum for
rapid clonal propagation of turmeric. A concentration of 2.5-3.0 mg/l of
2,4-dichlorophenoxy-acetic acid (2,4-D) was found to be optimum for callus
induction. Regeneration of plantlets from a callus was successfully conducted in
MS medium supplemented with standard growth hormones for multiplication at 25
+/- 2 degrees C under a 16 h photoperiod. These plantlets were successfully
transferred to the field. Plantlets (4-month-old) were incubated in a medium
containing different concentrations of sucrose supplemented with NAA (0.1 mg/l)
and Kn (1.0 mg/l) at 27 +/- 2 degrees C under an 8 h photoperiod for induction
of rhizomes. In vitro rhizome formation was observed in media containing 6 and
8% sucrose.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't

PMID: 11393773 [PubMed - indexed for MEDLINE]

217: Carcinogenesis. 2001 May;22(5):821-5.

Curcumin modifies Apc(min) apoptosis resistance and inhibits 2-amino
1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induced tumour formation in
Apc(min) mice.

Collett GP, Robson CN, Mathers JC, Campbell FC.

Department of Surgery, The Cancer Centre, Queen's University Belfast.

Curcumin, the active ingredient of the rhizome of Curcuma longa, promotes
apoptosis and may have chemopreventive properties. This study investigates the
effects of curcumin on apoptosis and tumorigenesis in male Apc(min) mice treated
with the human dietary carcinogen,
2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Intestinal epithelial
apoptotic index in response to PhIP treatment was approximately twice as great
in the wild-type C57BL/6 APC(+/+) strain than in Apc(min) mice (3.7% Apc(+/+)
versus 1.9% Apc(min); P < 0.001). PhIP promoted tumour formation in Apc(min)
proximal small intestine (4.6 tumours per mouse, PhIP treated versus 2.1 tumours
per mouse, control untreated; P < 0.05). Curcumin enhanced PhIP-induced
apoptosis (4.0% curcumin + PhIP versus 2.1% PhIP alone; P < 0.01) and inhibited
PhIP-induced tumorigenesis in the proximal small intestine of Apc(min) mice (2.2
tumours per mouse, curcumin + PhIP versus 4.6 tumours per mouse PhIP alone; P <
0.05). This study shows that the Apc(min) genotype is associated with resistance
to PhIP-induced apoptosis in intestinal epithelium. Curcumin attenuates Apc(min)
resistance to PhIP-induced apoptosis and inhibits PhIP-induced tumorigenesis in
proximal Apc(min) mouse small intestine.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11323404 [PubMed - indexed for MEDLINE]

218: Neurosci Lett. 2001 Apr 27;303(1):57-61.

Curcuminoids from Curcuma longa L. (Zingiberaceae) that protect PC12 rat
pheochromocytoma and normal human umbilical vein endothelial cells from
betaA(1-42) insult.

Kim DS, Park SY, Kim JK.

The Program for Collaborative Research in Pharmaceutical Science, College of
Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL
60612, USA. [email protected]

beta-Amyloid (betaA) induced oxidative stress is a well-established pathway of
neuronal cell death in Alzheimer's disease. From turmeric, Curcuma longa L.
(Zingiberaceae), three curcuminoids, curcumin, demethoxycurcumin, and
bisdemethoxycurcumin, were found to protect PC12 rat pheochromocytoma and normal
human umbilical vein endothelial (HUVEC) cells from betaA(1-42) insult, as
measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide
reduction assay. ED(50) values of curcumin, demethoxycurcumin, and
bisdemethoxycurcumin toward PC12 and HUVEC cells were 7.1+/-0.3, 4.7+/-0.1,
3.5+/-0.2 microg/ml and 6.8+/-0.4, 4.2+/-0.3, and 3.0+/-0.3 microg/ml,
respectively. These compounds were better antioxidants than alpha-tocopherol as
determined by DPPH radical trapping experiment. alpha-Tocopherol did not protect
the cells from betaA(1-42) insult even at>50 microg/ml concentration. The
results suggest that these compounds may be protecting the cells from
betaA(1-42) insult through antioxidant pathway.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11297823 [PubMed - indexed for MEDLINE]

219: J Ethnopharmacol. 2001 Apr;75(1):25-32.

Curcuma longa activates NF-kappaB and promotes adhesion of neutrophils to human
umbilical vein endothelial cells.

Madan B, Gade WN, Ghosh B.

Molecular Immunology and Immunogenetics Laboratory, Centre for Biochemical
Technology, University of Delhi Campus (North), Mall Road, Delhi 110 007, India.

Upregulation of expression of cell adhesion molecules, such as ICAM-1, VCAM-1
and E-selectin, is important for immune surveillance. Extravasation and
migration of body's effector cells to the site of immune activation is
controlled by the expression of cell adhesion molecules on endothelial cells. We
demonstrate here that an aqueous extract prepared from Curcuma longa (ClAqE), a
dietary component, promotes the adhesion of peripheral neutrophils to human
umbilical vein endothelial cells. To delineate the mechanism of increased
adhesion, we investigated the possibility that ClAqE induces the expression of
ICAM-1 and E-selectin on endothelial cells. ClAqE increases the steady state
transcript levels of ICAM-1, VCAM-1, and E-selectin as determined by RT-PCR. We
also show that ClAqE activates nuclear transcription factor NF-kappaB, a major
transcription factor involved in the transcription of genes encoding ICAM-1,
VCAM-1 and E-selectin. These results have implications for the usage of aqueous
preparation of C. longa for upregulation of cell adhesion molecule expression
and/or NF-kappaB.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11282439 [PubMed - indexed for MEDLINE]

220: Zhongguo Zhong Yao Za Zhi. 1997 Nov;22(11):655-7, 702.

[Contents of free amino acids and water-soluble carbohydrates in Curcuma longa
L. at different stages of growth]

[Article in Chinese]

Li L, Zhang Y, Liao G.

Sichuan Institute of Chinese Materia Medica, Chongqing 630065.

Closely related to the development of plant organs, the contents of free amino
acids and water-soluble carbohydrates in Curcuma longa vary with the course of
growth. The ratio of the two contents rises with the growing periods, and
reaches a maximum in the later stages of growth.

Publication Types:
English Abstract

PMID: 11243180 [PubMed - indexed for MEDLINE]

221: BMC Cancer. 2001;1:1. Epub 2001 Jan 17.

Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression
by dietary curcumin.

Limtrakul P, Anuchapreeda S, Lipigorngoson S, Dunn FW.

Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang
Mai, Thailand 50200. [email protected]

BACKGROUND: We investigated the chemopreventive action of dietary curcumin on
7,12-dimethylbenz(a)anthracene (DMBA)-initiated and
12,0-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation in
Swiss albino mice. Curcumin, a yellow coloring matter isolated from roots of
Curcuma longa Linn, is a phenolic compound possessing antioxidant, free radical
scavenger, and antiinflammatory properties. It has been shown by previously
reported work that TPA-induced skin tumors were inhibited by topical application
of curcumin, and curcumin has been shown to inhibit a variety of biological
activities of TPA. Topical application of curcumin was reported to inhibit
TPA-induced c-fos, c-jun and c-myc gene expression in mouse skin. This paper
reports the effects of orally administered curcumin, which was consumed as a
dietary component at concentrations of 0.2 % or 1 %, in ad libitum feeding.
RESULTS: Animals in which tumors had been initiated with DMBA and promoted with
TPA experienced significantly fewer tumors and less tumor volume if they
ingested either 0.2% or 1% curcumin diets. Also, the dietary consumption of
curcumin resulted in a significantly decreased expression of ras and fos
proto-oncogenes in the tumorous skin, as measured by enhanced chemiluminesence
Western blotting detection system (Amersham). CONCLUSIONS: Whereas earlier work
demonstrated that topical application of curcumin to mouse skin inhibited
TPA-induced expression of c-fos, c-jun and c-myc oncogenes, our results are the
first to show that orally consumed curcumin significantly inhibited DMBA- and
TPA-induced ras and fos gene expression in mouse skin.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11231886 [PubMed - indexed for MEDLINE]

222: J Nutr Biochem. 2000 Oct;11(10):509-14.

Changes in the prostaglandin levels in alcohol toxicity: effect of curcumin and
N-acetylcysteine.

Rajakrishnan V, Jayadeep A, Arun OS, Sudhakaran PR, Menon VP.

Department of Biochemistry, Annamalai University, Annamalainagar, Tamil Nadu,
India.

The present study was undertaken to evaluate the potential role of curcumin, the
antioxidant principal from Curcuma longa Linn., and the sulphur-containing amino
acid N-acetylcysteine against ethanol-induced changes in the levels of
prostanoids. Biochemical assessment of liver damage was done by measuring the
activities of serum enzymes (i.e., aspartate transaminase and alkaline
phosphatase), which were significantly increased in rats fed ethanol, whereas
the elevated levels of these enzymes were decreased after curcumin and
N-acetylcysteine treatment to rats fed ethanol. We observed a significant
increase in the levels of prostaglandins E(1), E(2), F(2alpha), and D(2) in
liver, kidney, and brain. Administration of curcumin and N-acetylcysteine was
shown to decrease the level of these prostanoids in the tissue studied.

PMID: 11120449 [PubMed]

223: Photochem Photobiol. 2000 Nov;72(5):625-31.

Effect of solvent on the excited-state photophysical properties of curcumin.

Khopde SM, Priyadarsini KI, Palit DK, Mukherjee T.

Radiation Chemistry & Chemical Dynamics Division, Bhabha Atomic Research Center,
Trombay, Mumbai, India.

Photophysical properties of curcumin, 1,7-bis-(4-hydroxy-3-methoxy
phenyl)-1,6-heptadiene-2,5-dione, a pigment found in the rhizomes of Curcuma
longa (turmeric) have been studied in different kinds of organic solvent and
also in Triton X-100 aqueous micellar media using time-resolved fluorescence and
transient absorption techniques having pico and nanosecond time resolution, in
addition to steady-state absorption and fluorescence spectroscopic techniques.
Steady-state absorption and fluorescence characteristics of curcumin have been
found to be sensitive to the solvent characteristics. Large change (delta mu =
6.1 Debye) in dipole moments due to photoexcitation to the excited singlet state
(S1) indicates strong intramolecular charge transfer character of the latter.
Curcumin is a weakly fluorescent molecule and the fluorescence decay properties
in most of the solvents could be fitted well to a double-exponential decay
function. The shorter component having lifetime in the range 50-350 ps and
percent contribution of amplitude more than 90% in different solvents may be
assigned to the enol form, whereas the longer component, having lifetime in the
range 500-1180 ps with less than 10% contribution may be assigned to the di-keto
form of curcumin. Our nuclear magnetic resonance study in CDCl3 and dimethyl
sulfoxide-D6 also supports the fact that the enol form is present in the
solution by more than about 95% in these solvents. Excited singlet (S1) and
triplet (T1) absorption spectrum and decay kinetics have been characterized by
pico and nanosecond laser flash photolysis. Quantum yield of the triplet is low
(phi T < or = 0.12). Both the fluorescence and triplet quantum yields being low
(phi f + phi T < 0.18), the photophysics of curcumin is dominated by the energy
relaxation mechanism via the internal conversion process.

PMID: 11107847 [PubMed - indexed for MEDLINE]

224: Mech Ageing Dev. 2000 Oct 20;119(1-2):41-7.

An hydroalcoholic extract of curcuma longa lowers the apo B/apo A ratio.
Implications for atherogenesis prevention.

Ramirez-Bosca A, Soler A, Carrion MA, Diaz-Alperi J, Bernd A, Quintanilla C,
Quintanilla Almagro E, Miquel J.

A.S.A.C. Pharmaceutical International A.I.E., C/ Sagitario 14, 03006, Alicante,
Spain.

It is generally accepted that free-radical induced blood lipid peroxidation and
especially peroxidized LDL play a central role in the pathogenesis of
atherosclerosis and related cardiovascular disease. Moreover, recent research
highlights the key contribution of apolipoprotein B (apo B) to atherogenesis as
the main inductor of one of its earlier steps, i.e. macrophage proliferation.
This has led us to investigate the apo B response to a very effective phenolic
lipid-antioxidant, namely an hydroalcoholic extract of Curcuma longa, which
according to our previous work does not show any toxic effects and decreases the
levels of blood lipid peroxides, oxidized lipoproteins and fibrinogen. The
present study shows that a daily oral administration of the extract decreases
significantly the LDL and apo B and increases the HDL and apo A of healthy
subjects. This and recent data on the increased anti-atherogenic action of the
physiological antioxidant tocopherol in the presence of phenolic co-antioxidants
(which eliminate the tocopheroxyl radical), justifies planned clinical research
to test the usefulness of the curcuma extract as a co-antioxidant complement to
standard treatments to prevent or retard atherosclerosis.

PMID: 11040400 [PubMed - indexed for MEDLINE]

225: Zhongguo Zhong Yao Za Zhi. 1997 Oct;22(10):587-90, 638-9.

[Ontogeny of Curcuma longa L.]

[Article in Chinese]

Li L, Zhang Y, Qin S, Liao G.

Sichuan Institute of Chinese Materia Medica, Chongqing.

Based on the research of growth of organs, accumulation of dry matter,
distribution of photosynthetic production and displacement of growth centre, the
growth of turmeric can be divided into three stages. There are 13 leaves in the
life of turmeric. Leaf formation takes place rapidly to form 8 leaves in the
seedling stage. The leaf area and increase of dry matter per day in roots and
leaves are smaller or lower in the seedling stage. In the daughter rhizome
formation stage, NAR reaches the maximum (3.54/m2.d), and the leaf area reaches
the maximum(3302.9 cm2/plant, LAI 4.95). Before the daughter rhizome formation
stage, more than 75% of dry matters are distributed in leaves, and in the
daughter rhizome formation stage, 50%-75% of dry matters are distrbuted in
leaves. In the late growing period, more than 40% of dry matters are distributed
in the daughter rhizome. The growth centre of turmeric changes two times in
life. When CGRr is equal to CGRt, the crossing of CGRt and CGRr curves may be
regarded as the evidence of the transfer of growth centre from leaves to
daughter rhizome.

Publication Types:
English Abstract

PMID: 11038924 [PubMed - indexed for MEDLINE]

226: Food Chem Toxicol. 2000 Nov;38(11):991-5.

Inhibition by curcumin of diethylnitrosamine-induced hepatic hyperplasia,
inflammation, cellular gene products and cell-cycle-related proteins in rats.

Chuang SE, Cheng AL, Lin JK, Kuo ML.

Division of Cancer Research, National Health Research Institute, Taipei, Taiwan.

Curcumin (CCM), a major yellow pigment of turmeric obtained from powdered
rhizomes of the plant Curcuma longa Linn, is commonly used as coloring agent in
foods, drugs and cosmetics. In this study we report that gavage administration
of 200 mg/kg or 600 mg/kg CCM effectively suppressed diethylnitrosamine
(DEN)-induced liver inflammation and hyperplasia in rats, as evidenced by
histopathological examination. Immunoblotting analysis showed that CCM strongly
inhibited DEN-mediated the increased expression of oncogenic p21(ras) and p53
proteins in liver tissues of rats. In cell-cycle-related proteins, CCM
selectively reduced the expression of proliferating cell nuclear antigen (PCNA),
cyclin E and p34(cdc2), but not Cdk2 or cyclin D1. Moreover, CCM also inhibited
the DEN-induced increase of transcriptional factor NF-kappa B. However, CCM
failed to affect DEN-induced c-Jun and c-Fos expression. It has become widely
recognized that the development of human hepatocellular carcinoma (HCC) is
predominantly due to the chronic inflammation by virus, bacteria or chemical.
Our results suggest a potential role for CCM in the prevention of HCC.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11038236 [PubMed - indexed for MEDLINE]

227: FEBS Lett. 2000 Oct 13;483(1):78-82.

Differential modulation of nitric oxide production by curcumin in host
macrophages and NK cells.

Bhaumik S, Jyothi MD, Khar A.

Centre for Cellular and Molecular Biology, Uppal Road, 500 007, Hyderabad,
India.

Curcumin, the yellow pigment from Curcuma longa, has been shown to possess
tumoricidal activity. We have earlier reported the induction of apoptosis in
AK-5, rat histiocytic cells by curcumin leading to the inhibition of tumor
growth in vivo. In this study we have observed differential activation status in
host macrophages and NK cells induced by curcumin during the spontaneous
regression of subcutaneously transplanted AK-5 tumors. Closer scrutiny of the
cytokine profile and nitric oxide (NO) production by immune cells showed an
initial downregulation of Th1 cytokine response and NO production by
macrophages, and their upregulation in NK cells, which picked-up upon prolonged
treatment with curcumin, culminating in a stronger tumoricidal effect. These
studies suggest that the host macrophages and NK cells play an important
modulatory role in the remission of AK-5 tumor.

PMID: 11033360 [PubMed - indexed for MEDLINE]

228: Int J Mol Med. 2000 Nov;6(5):521-6.

Curcumin inhibits lipoxygenase by binding to its central cavity: theoretical and
X-ray evidence.

Skrzypczak-Jankun E, McCabe NP, Selman SH, Jankun J.

Instrumentation Center, College of Art and Sciences, The University of Toledo,
Toledo, OH 43606, USA.

Many lipoxygenase inhibitors including curcumin are currently being studied for
their anti-carcinogenic properties. Curcumin is a naturally occurring
polyphenolic phytochemical isolated from the powdered rhizome of the plant
Curcuma longa that possesses anti-inflammatory properties and inhibits cancer
formation in mice. Recently it was shown that the soybean lipoxygenase L1
catalyzed the oxygenation of curcumin and that curcumin can act as a
lipoxygenase substrate. In the current study, we investigated the fate of
curcumin when used as a soybean lipoxygenase L3 substrate. By use of X-ray
diffraction and mass spectrometry, we found an unoccupied electron mass that
appears to be an unusual degradation product of curcumin
(4-hydroxyperoxy-2-methoxyphenol) located near the soybean L3 catalytic site.
Understanding how curcumin inhibits lipoxygenase may help in the development of
novel anti-cancer drugs used for treatment where lipoxygenases are involved.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11029517 [PubMed - indexed for MEDLINE]

229: Jpn J Cancer Res. 2000 Sep;91(9):893-8.

Chemopreventive effect of curcumin on N-nitrosomethylbenzylamine-induced
esophageal carcinogenesis in rats.

Ushida J, Sugie S, Kawabata K, Pham QV, Tanaka T, Fujii K, Takeuchi H, Ito Y,
Mori H.

1st Department of Pathology, Gifu University School of Medicine, Tsukasa-machi,
Gifu 500-8705, Japan. [email protected]

Modifying effects of curcumin (derived from the rhizome of Curcuma longa L.)
during the initiation or post-initiation phase of N-nitrosomethylbenzylamine
(NMBA)-induced esophageal carcinogenesis were investigated in male F344 rats.
Five-week-old rats were divided into 5 groups, and groups 1, 2 and 3 were given
intraperitoneal injections of NMBA (0.5 mg / kg body weight / injection 15
times) for 5 weeks from 7 weeks old to induce esophageal neoplasms. Groups 2 and
3 were fed the diet containing 500 ppm curcumin during the initiation and
post-initiation phases, respectively. Group 4 was given the diet containing
curcumin throughout the experiment, and group 5 was kept on the basal diet alone
and served as an untreated control. Incidence and multiplicity of esophageal
neoplasms of group 1 (NMBA alone) were 66.7% and 0.83 +/- 0.70, respectively.
Those of groups 2 and 3 were significantly less than those of group 1 (39.3%,
0.46 +/- 0.64, P < 0.05; 33.3%, 0.36 +/- 0.56, P < 0.05, respectively).
Furthermore, the incidence and multiplicity of esophageal preneoplastic lesions
(moderate or severe epithelial dysplasia) of group 2 (57.1%, 0.61 +/- 0.57; 40%,
0.29 +/- 0.46) or 3 (56.7%, 0.67 +/- 0.66; 23.3%, 0.23 +/- 0.43) were less than
those of group 1 (100%, 1.67 +/- 0.70; 70.8%, 0.92 +/- 0.72) (P < 0.05). In this
experiment, feeding of curcumin significantly decreased the expression of cell
proliferation biomarkers (5-bromo-2'-deoxyuridine labeling index) in the
non-lesional esophageal epithelium (P < 0.01). These findings indicate that
curcumin inhibits NMBA-induced esophageal carcinogenesis when given during the
post initiation as well as initiation phase. This inhibition may be related to
suppression of the increased cell proliferation induced by NMBA in the
esophageal epithelium.

PMID: 11011116 [PubMed - indexed for MEDLINE]

230: Phytomedicine. 2000 Jul;7(4):303-8.

Cytotoxicity, antioxidant and anti-inflammatory activities of curcumins I-III
from Curcuma longa.

Ramsewak RS, DeWitt DL, Nair MG.

Department of Horticulture and National Food Safety and Toxicology Center,
Michigan State University, East Lansing 48824, USA.

Curcumin I, curcumin II (monodemethoxycurcumin) and curcumin III
(bisdemethoxycurcumin) from Curcuma longa were assayed for their cytotoxicity,
antioxidant and anti-inflammatory activities. These compounds showed activity
against leukemia, colon, CNS, melanoma, renal, and breast cancer cell lines. The
inhibition of liposome peroxidation by curcumins I-III at 100 microg/ml were 58,
40 and 22%, respectively. The inhibition of COX-I and COX-II enzymes by the
curcumins was observed. Curcumins I-III were active against COX-I enzyme at 125
microg/ml and showed 32, 38.5 and 39.2% inhibition of the enzyme, respectively.
Curcumins I-III also showed good inhibition of the COX-II enzyme at 125 mg/ml
with 89.7, 82.5 and 58.9% inhibition of the enzyme, respectively.

Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

PMID: 10969724 [PubMed - indexed for MEDLINE]

231: Phytother Res. 2000 Sep;14(6):443-7.

Role of curcumin in idiopathic inflammatory orbital pseudotumours.

Lal B, Kapoor AK, Agrawal PK, Asthana OP, Srimal RC.

Department of Ophthalmology, K.G. Medical College, Lucknow, India.

The present report, describes for the first time the clinical efficacy of
curcumin, the active constituent of rhizomes of Curcuma longa, in the treatment
of patients suffering from idiopathic inflammatory orbital pseudotumours.
Curcumin was administered orally at a dose of 375 mg/3 times/day orally for a
period of 6-22 months in eight patients. They were followed up for a period of 2
years at 3 monthly intervals. Five patients completed the study, out of which
four recovered completely and in one patient the swelling regressed completely
but some limitation of movement persisted. No side effect was noted in any
patient and there was no recurrence. It is suggested that curcumin could be used
as a safe and effective drug in the treatment of idiopathic inflammatory orbital
pseudotumours. Copyright 2000 John Wiley & Sons, Ltd.

PMID: 10960899 [PubMed - indexed for MEDLINE]

232: Microbios. 2000;102(403):165-73.

Antifungal potential of some higher plants against Fusarium udum causing wilt
disease of Cajanus cajan.

Singh R, Rai B.

Soil Microbiology and Ecopathology Laboratory, Centre of Advanced Study in
Botany, Banaras Hindu University, Varanasi, India.

The fungitoxic effects of different plant extracts on Fusarium udum, which
causes wilt disease of Cajanus cajan in vitro and in vivo, were examined. The
complete arrest of the radial growth of the pathogen occurred at a 10%
concentration of leaf extract from Adenocallyma alliaceum. A leaf extract of
Citrus medica, a root extract of Asparagus adscendens, rhizome extracts of
Curcuma longa and Zingiber officinale, and a bulb extract of Allium sativum
inhibited up to 100% growth at higher concentrations. A. alliaceum controlled
the disease up to 100% by amending its 4% powder in unsterilized soil and 2% in
sterilized soil. The population of F. udum was found to be markedly reduced
following treatments with plant powders.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10955831 [PubMed - indexed for MEDLINE]

233: J Ethnopharmacol. 2000 Jul;71(1-2):23-43.

Review on some plants of Indian traditional medicine with antioxidant activity.

Scartezzini P, Speroni E.

Department of Pharmacology, University of Bologna, Via Irnerio, 48, 40126,
Bologna, Italy.

A lot of medicinal plants, traditionally used for thousands of years, are
present in a group of herbal preparations of the Indian traditional health care
system (Ayurveda) named Rasayana proposed for their interesting antioxidant
activities. Among the medicinal plants used in ayurvedic Rasayana for their
therapeutic action, some of these have been throughly investigated. In the
present paper seven plants (Emblica officinalis L., Curcuma longa L., Mangifera
indica L., Momordica charantia L., Santalum album L., Swertia chirata Buch-Ham,
Withania somnifera (L.) Dunal) are viewed for their historical, etymological,
morphological, phytochemical and pharmacological aspects. The plants described
contain antioxidant principles, that can explain and justify their use in
traditional medicine in the past as well as the present. In order to identify
the plants with antioxidant activity in Ayurveda, a formulation of some
rasayanas with well defined antioxidant properties has been examinated. For this
purpose, we have considered Sharma's work on the preparation MAK4, MAK5, MA631,
MA 471, MA Raja's Cup, MA Student Rasayana, MA Ladies Rasayana.

Publication Types:
Review

PMID: 10904144 [PubMed - indexed for MEDLINE]

234: J Agric Food Chem. 2000 Jun;48(6):2189-92.

Supercritical carbon dioxide extraction of turmeric (Curcuma longa).

Gopalan B, Goto M, Kodama A, Hirose T.

Department of Applied Chemistry and Biochemistry, Kumamoto University, Japan.

Turmeric oil was extracted from turmeric (Curcuma longa) with supercritical
carbon dioxide in a semicontinuous-flow extractor. Extraction rate was measured
as a function of pressure, temperature, flow rate, and particle size. The
extraction rate increased with an increase in CO(2) flow rate and with a
reduction of particle size. The effect of pressure and temperature on turmeric
extraction suggested the use of higher pressure and lower temperature at which
solvent density is greater and thus the solubility of the oil in the solvent is
greater in the range of 313-333 K and 20-40 MPa. The major components (
approximately 60%) of the extracted oil were identified as turmerone and
ar-turmerone by GC-MS.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10888520 [PubMed - indexed for MEDLINE]

235: Planta Med. 2000 May;66(4):396-8.

A simple and efficient separation of the curcumins, the antiprotozoal
constituents of Curcuma longa.

Rasmussen HB, Christensen SB, Kvist LP, Karazmi A.

A simple and efficient method for the separation of the three phenolic
diketones, curcumin 1, demethoxycurcumin 2, and bis-demethoxycurcumin 3,
isolated from the rhizomes of Curcuma longa has been developed. The method is of
general applicability for the separation of compounds containing acidic and
chelating groups and is amenable to large scale separations. The curcumins 1-3
show moderate activity against Plasmodium falciparum (IC50: 3.5, 4.2 and 3.0
micrograms/ml) and Leishmania major (IC50: 7.8, 14.1 and 21.5 micrograms/ml)
respectively.

Publication Types:
Letter

PMID: 10865470 [PubMed - indexed for MEDLINE]

236: Mech Ageing Dev. 2000 Apr 14;114(3):207-10.

An hydroalcoholic extract of Curcuma longa lowers the abnormally high values of
human-plasma fibrinogen.

Ramirez Bosca A, Soler A, Carrion-Gutierrez MA, Pamies Mira D, Pardo Zapata J,
Diaz-Alperi J, Bernd A, Quintanilla Almagro E, Miquel J.

A.S.A.C. Pharmaceutical International, A.I.E. Alicante, C/Sagitario, 14, 03006,
Alicante, Spain.

Publication Types:
Clinical Trial

PMID: 10802125 [PubMed - indexed for MEDLINE]

237: J Biol Chem. 2000 May 26;275(21):15601-4.

L-929 cells harboring ectopically expressed RelA resist curcumin-induced
apoptosis.

Anto RJ, Maliekal TT, Karunagaran D.

Division of Cancer Biology, Rajiv Gandhi Center for Biotechnology,
Thiruvananthapuram, Kerala-695014, India.

Curcumin (diferuloyl methane), the yellow pigment in turmeric (Curcuma longa),
is a potent chemopreventive agent. Curcumin induces apoptosis of several, but
not all, cancer cells. Many cancer cells protect themselves against apoptosis by
activating nuclear factor-kappaB (NF-kappaB)/Rel, a transcription factor that
helps in cell survival. Signal-induced activation of NF-kappaB is known to be
inhibited by curcumin. To understand the role of NF-kappaB in curcumin-induced
apoptosis, we stably transfected relA gene encoding the p65/RelA subunit of
NF-kappaB, into l-929 cells (mouse fibrosarcoma) and the relA-transfected cells
were resistant to varying doses of curcumin (10(-6)-10(-4) m), whereas the
parental cells underwent apoptosis in a time- and dose-dependent manner. The
relA-transfected cells showed constitutive NF-kappaB DNA binding activity that
could not be inhibited by curcumin and did not show nuclear condensation and DNA
fragmentation upon treatment with curcumin. When a super-repressor form of
IkappaB-alpha (known to inhibit NF-kappaB) was transfected transiently into
relA-transfected cells, the cells were no longer resistant to curcumin. Our
results highlight a critical anti-apoptotic role for NF-kappaB in
curcumin-induced apoptosis.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10747850 [PubMed - indexed for MEDLINE]

238: J Ethnopharmacol. 1999 Oct;67(1):1-6.

Ferula asa-foetida and Curcuma longa in traditional medical treatment and diet
in Nepal.

Eigner D, Scholz D.

Institute for Tibetology and Buddhist Studies, Vienna, Austria.

Food and eating have powerful symbolic value among the hinduistically-influenced
ethnic groups of Nepal. In addition, food plays a major role in the concepts of
illness and curing and constitute an integral part of traditional medical
prescriptions. Materials that are consumed in 0.5-1.5 g amounts in the daily
diet (e.g. the spices turmeric and asafoetida) are used in minute amounts for
medical purposes. Why? Three hypotheses are offered here to discuss this issue.

Publication Types:
Review

PMID: 10616954 [PubMed - indexed for MEDLINE]

239: Int J Immunopharmacol. 1999 Nov;21(11):745-57.

Curcuma longa inhibits TNF-alpha induced expression of adhesion molecules on
human umbilical vein endothelial cells.

Gupta B, Ghosh B.

Molecular Immunology and Immunogenetics Laboratory, Centre for Biochemical
Technology, University of Delhi, India.

Identification of non-steroidal anti-inflammatory small molecules is very
important for the development of anti-inflammatory drugs. We demonstrate here
that out of three compounds, viz diferuloylmethane, p-coumaroylferuloylmethane
and di-p-coumaroylmethane, present in the ethyl acetate extract of Curcuma
longa, diferuloylmethane is most potent in inhibiting TNF-alpha induced
expression of ICAM-1, VCAM-1 and E-selectin on human umbilical vein endothelial
cells. The inhibition by diferuloylmethane is time dependent and is reversible.
By using RT-PCR, we demonstrate that it inhibits the induction of steady state
transcript levels of ICAM-1, VCAM-1 and E-selectin, and therefore it may
interfere with the transcription of their genes. As diferuloylmethane
significantly blocks the cytokine induced transcript levels for the leukocyte
adhesion molecules, it may be interfering at an early stage of signalling event
induced by TNF-alpha.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10576620 [PubMed - indexed for MEDLINE]

240: Planta Med. 1999 Oct;65(7):610-3.

Choleretic effects of curcuminoids on an acute cyclosporin-induced cholestasis
in the rat.

Deters M, Siegers C, Muhl P, Hansel W.

Institute of Experimental and Clinical Pharmacology and Toxicology, Rostock,
Germany.

Former studies have shown that curcumin, which can be extracted from different
Curcuma species, is able to stimulate bile flow in rats, whereas
bisdemethoxycurcumin, which is mainly found in rhizomes of Curcuma longa, is
believed to inhibit bile flow. To reevaluate this observation we investigated
the influence of both curcuminoids on bile flow, bile acid concentration and
excretion over a time period of 180 min in the bile fistula model in rats.
Furthermore, we tested the ability of both curcuminoids to reduce
cyclosporin-induced cholestasis. 30 min after intravenous injection of 25 mg/kg
of curcumin and bisdemethoxycurcumin bile flow was enhanced from 500
microliters/kg/15 min (100%) to 180% and to 220%, respectively. The choleretic
effect of bisdemethoxycurcumin lasted longer than that of curcumin. Following
intravenous injection of 30 mg/kg of cyclosporin, which reduced bile flow, bile
acid concentration (15 mmol/l) and excretion (12.5 mumol/kg/15 min) to 40% of
the initial value, administration of curcumin and bisdemethoxycurcumin
transiently increased bile flow to 100% and to 125% of the starting value,
respectively. However, only bisdemethoxycurcumin statistically significantly
attenuated cyclosporin-induced reduction of bile acid excretion. We conclude
that the beneficial properties of curcuminoids for the therapy of
cyclosporin-induced cholestasis still remain to be proven.

Publication Types:
Comparative Study

PMID: 10575375 [PubMed - indexed for MEDLINE]

241: Immunol Invest. 1999 Sep-Dec;28(5-6):291-303.

Immunomodulatory activity of curcumin.

Antony S, Kuttan R, Kuttan G.

Amala Cancer Research Centre, Amala Nagar, Kerala, India.

Curcumin, an active ingredient present in Curcuma longa, was analysed for the
immunomodulatory activity in Balb/c mice. Curcumin administration was found to
increase the total WRC count (15,290) significantly on the 12th day Group of
animals treated with vehicle alone showed results similar to that of normal
animal (10,130 on 12th day). Curcumin increased the circulating antibody titre
(512) against SRBC. Curcumin administration increased the plaque forming cells
(PFC) in the spleen and the maximum number of PFC was observed on the 6th day
(1,130 PFC/10(6) spleen cells) after immunization with SRBC. Rone marrow
cellularity (16.9x10(6) cells/femur) and alpha-esterase positive cells
(1,622/4000 cells) were also enhanced by Curcumin administration. A significant
increase in macrophage phagocytic activity was also observed in Curcumin treated
animals (P<0.001). These results indicate the immunostimulatory activity of
Curcumin.

PMID: 10574627 [PubMed - indexed for MEDLINE]

242: Atherosclerosis. 1999 Dec;147(2):371-8.

Oral administration of a turmeric extract inhibits LDL oxidation and has
hypocholesterolemic effects in rabbits with experimental atherosclerosis.

Ramirez-Tortosa MC, Mesa MD, Aguilera MC, Quiles JL, Baro L, Ramirez-Tortosa CL,
Martinez-Victoria E, Gil A.

Department of Biochemistry and Molecular Biology, University of Granada, Faculty
of Pharmacy, Campus de Cartuja 18071, Granada, Spain. [email protected]

The oxidation of low-density lipoproteins (LDL) plays an important role in the
development of atherosclerosis. Curcumin is a yellow pigment obtained from
rhizomes of Curcuma longa and is commonly used as a spice and food colouring.
Curcumin and turmeric extracts have several pharmacological effects including
antitumour, anti-inflammatory, antioxidant and antiinfectious activities
although the precise mechanisms involved remain to be elicited. We evaluated the
effect of an ethanol-aqueous extract obtained from rhizomes of C. longa on LDL
oxidation susceptibility and plasma lipids in atherosclerotic rabbits. A total
of 18 rabbits were fed for 7 weeks on a diet containing 95.7% standard chow, 3%
lard and 1. 3% cholesterol, to induce atherosclerosis. The rabbits were divided
into groups, two of which were also orally treated with turmeric extract at
doses of 1.66 (group A) and 3.2 (group B) mg/kg body weight, respectively. A
third group (group C) acted as a control. Plasma and LDL lipid composition,
plasma alpha-tocopherol, plasma retinol, LDL TBARS, LDL lipid hydroperoxides and
analysis of aortic atherosclerotic lesions were assayed. The low but not the
high dosage decreased the susceptibility of LDL to lipid peroxidation. Both
doses had lower levels of total plasma cholesterol than the control group.
Moreover, the lower dosage had lower levels of cholesterol, phospholipids and
triglycerides in LDL than the 3.2-mg dosage. In conclusion, the use of this
extract could be useful in the management of cardiovascular disease in which
atherosclerosis is important.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 10559523 [PubMed - indexed for MEDLINE]

243: Wound Repair Regen. 1999 Sep-Oct;7(5):362-74.

Curcumin enhances wound healing in streptozotocin induced diabetic rats and
genetically diabetic mice.

Sidhu GS, Mani H, Gaddipati JP, Singh AK, Seth P, Banaudha KK, Patnaik GK,
Maheshwari RK.

Center for Combat and Life Sustainment Research, Uniformed Services University
of Health Sciences, Bethesda, MD 20814, USA. [email protected]

Tissue repair and wound healing are complex processes that involve inflammation,
granulation and tissue remodeling. Interactions of different cells,
extracellular matrix proteins and their receptors are involved in wound healing,
and are mediated by cytokines and growth factors. Previous studies from our
laboratory have shown that curcumin (diferuloylmethane), a natural product
obtained from the rhizomes of Curcuma longa, enhanced cutaneous wound healing in
rats and guinea pigs. In this study, we have evaluated the efficacy of curcumin
treatment by oral and topical applications on impaired wound healing in diabetic
rats and genetically diabetic mice using a full thickness cutaneous punch wound
model. Wounds of animals treated with curcumin showed earlier
re-epithelialization, improved neovascularization, increased migration of
various cells including dermal myofibroblasts, fibroblasts, and macrophages into
the wound bed, and a higher collagen content. Immunohistochemical localization
showed an increase in transforming growth factor-beta1 in curcumin-treated
wounds compared to controls. Enhanced transforming growth factor-beta1 mRNA
expression in treated wounds was confirmed by in situ hybridization, and laser
scan cytometry. A delay in the apoptosis patterns was seen in diabetic wounds
compared to curcumin treated wounds as shown by terminal deoxynucleotidyl
transferase-mediated deoxyuridyl triphosphate nick end labeling analysis.
Curcumin was effective both orally and topically. These results show that
curcumin enhanced wound repair in diabetic impaired healing, and could be
developed as a pharmacological agent in such clinical settings.

Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 10564565 [PubMed - indexed for MEDLINE]

244: Phytother Res. 1999 Nov;13(7):571-4.

Neuroprotective role of curcumin from curcuma longa on ethanol-induced brain
damage.

Rajakrishnan V, Viswanathan P, Rajasekharan KN, Menon VP.

Department of Biochemistry, Annamalai University, Annamalai Nagar-608 002,
India.

In the present study, curcumin from Curcuma longa was screened for
neuroprotective activity using ethanol as a model of brain injury. Oral
administration of curcumin to rats caused a significant reversal in lipid
peroxidation, brain lipids and produced enhancement of glutathione, a
non-enzymic antioxidant in ethanol intoxicated rats, revealing that the
antioxidative and hypolipidaemic action of curcumin is-responsible for its
protective role against ethanol induced brain injury. Copyright 1999 John Wiley
& Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10548748 [PubMed - indexed for MEDLINE]

245: Mutat Res. 1999 Jul 16;428(1-2):305-27.

Molecular mechanisms of chemopreventive effects of selected dietary and
medicinal phenolic substances.

Surh Y.

Laboratory of Biochemistry and Molecular Toxicology, College of Pharmacy, Seoul
National University, Shinlim-dong, Kwanak-gu, Seoul, South Korea.
[email protected]

Recently, considerable attention has been focused on identifying naturally
occurring chemopreventive substances capable of inhibiting, retarding, or
reversing the multi-stage carcinogenesis. A wide array of phenolic substances,
particularly those present in dietary and medicinal plants, have been reported
to possess substantial anticarcinogenic and antimutagenic activities. The
majority of these naturally occurring phenolics retain antioxidative and
anti-inflammatory properties which appear to contribute to their chemopreventive
or chemoprotective activity. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide),
a pungent ingredient of hot chili pepper, protects against
experimentally-induced mutagenesis and tumorigenesis. It also induces apoptosis
in various immortalized or malignant cell lines. Plants of ginger family
(Zingiberaceae) have been frequently and widely used as spices and also, in
traditional oriental medicine. Curcumin, a yellow ingredient from turmeric
(Curcuma longa L., Zingiberaceae), has been extensively investigated for its
cancer chemopreventive potential. Yakuchinone A
[1-(4'-hydroxy-3'-methoxyphenyl)-7-phenyl-3-heptanone] and yakuchinone B
[1-(4'-hydroxy-3'-methoxyphenyl)-7-phenylhept-1-en-3-one] present in Alpinia
oxyphylla Miquel (Zingiberaceae) have inhibitory effects on phorbol
ester-induced inflammation and skin carcinogenesis in mice, and oxidative stress
in vitro. These diarylheptanoids suppress phorbol ester-induced activation of
ornithine decarboxylase and production of tumor necrosis factor-alpha or
interleukin-1alpha and their mRNA expression. They also nullified the phorbol
ester-stimulated induction of activator protein 1 (AP-1) in cultured human
promyelocytic leukemia (HL-60) cells. In addition, both yakuchinone A and B
induced apoptotic death in HL-60 cells. Ginger (Zingiber officinale Roscoe,
Zingiberaceae) contains such pungent ingredients as [6]-gingerol and
[6]-paradol, which also have anti-tumor promotional and antiproliferative
effects. Resveratrol (3, 5,4'-trihydroxy-trans-stilbene), a phytoalexin found in
grapes and other dietary and medicinal plants, and (-)-epigallocatechin gallate,
a major antioxidative green tea polyphenol, exert striking inhibitory effects on
diverse cellular events associated with multi-stage carcinogenesis. In addition,
these compounds have ability to suppress proliferation of human cancer cells via
induction of apoptosis.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 10518003 [PubMed - indexed for MEDLINE]

246: Mutat Res. 1999 Jul 16;428(1-2):49-57.

Anti-tumor promoting potential of naturally occurring diarylheptanoids
structurally related to curcumin.

Chun KS, Sohn Y, Kim HS, Kim OH, Park KK, Lee JM, Moon A, Lee SS, Surh YJ.

College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-gu, Seoul,
South Korea.

In recent years, there have been considerable efforts to search for naturally
occurring substances for intervention of carcinogenesis. Many components from
medicinal or dietary plants have been identified to possess potential
chemopreventive properties. For instance, curcumin, a yellow colouring agent
from turmeric (Curcuma longa Linn., Zingiberaceae) has been shown to inhibit
tumor formation in diverse animal models. Alpinia oxyphylla Miquel that also
belongs to ginger family has been used in oriental herbal medicine. In the
present work, we have evaluated the anti-tumor promoting potential of
yakuchinone A (1-[4'-hydroxy-3'-methoxyphenyl]-7-phenyl-3-heptanone) and
yakuchinone B (1-[4'-hydroxy-3'-methoxyphenyl]-7-phenylhept-1-en-3-one), major
pungent ingredients of A. oxyphylla. Thus, topical application of yakuchinone A
or B significantly suppressed TPA-induced epidermal ornithine decarboxylase
activity. They also reduced TPA-stimulated production of tumor necrosis
factor-alpha in cultured human promyelocytic leukemia (HL-60) cells. Both
compounds blunted the TPA-induced superoxide generation in differentiated HL-60
cells in a concentration-related manner and also inhibited lipid peroxidation in
rat brain homogenates. Furthermore, yakuchinone A and yakuchinone B nullified
the activation of the activator protein-1 (AP-1) in immortalized mouse
fibroblast cells in culture. These findings indicate that pungent
diarylheptanoids from A. oxyphylla have anti-tumor promotional properties that
can contribute to their chemopreventive potential.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't

PMID: 10517978 [PubMed - indexed for MEDLINE]

247: Toxicol Lett. 1999 Sep 20;109(1-2):87-95.

The effect of curcumin on glutathione-linked enzymes in K562 human leukemia
cells.

Singhal SS, Awasthi S, Pandya U, Piper JT, Saini MK, Cheng JZ, Awasthi YC.

Department of Internal Medicine, The University of Texas Medical Branch,
Galveston 77555, USA.

Curcumin, an antioxidant present in the spice turmeric (Curcuma longa), has been
shown to inhibit chemical carcinogenesis in animal models and has been shown to
be an anti-inflammatory agent. While mechanisms of its biological activities are
not understood, previous studies have shown that it modulates glutathione
(GSH)-linked detoxification mechanisms in rats. In the present studies, we have
examined the effects of curcumin on GSH-linked enzymes in K562 human leukemia
cells. One micromolar curcumin in medium (16 h) did not cause any noticeable
change in glutathione peroxidase (GPx), glutathione reductase, and
glucose-6-phosphate dehydrogenase activities. Gamma-glutamyl-cysteinyl
synthetase activity was induced 1.6-fold accompanied by a 1.2-fold increase in
GSH levels. GSH S-transferase (GST) activities towards
1-chloro-2,4-dinitrobenzene, and 4-hydroxynonenal (4HNE) were increased in
curcumin-treated cells 1.3- and 1.6-fold, respectively (P = 0.05). The GST
isozyme composition of K562 cells was determined as follows: 66% of GST Pl-1,
31% of Mu class GST(s), and 3% of an anionic Alpha-class isozyme hGST 5.8, which
was immunologically similar to mouse GSTA4-4 and displayed substrate preference
for 4HNE. The isozyme hGST 5.8 appeared to be preferentially induced by
curcumin, as indicated by a relatively greater increase in activity toward 4HNE.
Immunoprecipitation showed that GPx activity expressed by GST 5.8 contributed
significantly (approximately 50%) to the total cytosolic GPx activity of K562
cells to lipid hydroperoxides. Taken together, these results suggest that GSTs
play a major role in detoxification of lipid peroxidation products in K562
cells, and that these enzymes are modulated by curcumin.

Publication Types:
Research Support, U.S. Gov't, P.H.S.

PMID: 10514034 [PubMed - indexed for MEDLINE]

248: Br J Pharmacol. 1999 Sep;128(2):380-4.

Curcumin inhibits Th1 cytokine profile in CD4+ T cells by suppressing
interleukin-12 production in macrophages.

Kang BY, Song YJ, Kim KM, Choe YK, Hwang SY, Kim TS.

College of Pharmacy, Chonnam National University, Kwangju 500-757, South Korea.

1 Interleukin-12 (IL-12) plays a central role in the immune system by driving
the immune response towards T helper 1 (Th1) type responses which are
characterized by high IFN-gamma and low IL-4 production. In this study we
investigated the effects of curcumin, a natural product of plants obtained from
Curcuma longa (turmeric), on IL-12 production by mouse splenic macrophages and
the subsequent ability of these cells to regulate cytokine production by CD4+ T
cells. 2 Pretreatment with curcumin significantly inhibited IL-12 production by
macrophages stimulated with either lipopolysaccharide (LPS) or head-killed
Listeria monocytogenes (HKL). 3 Curcumin-pretreated macrophages reduced their
ability to induce IFN-gamma and increased the ability to induce IL-4 in
Ag-primed CD4+ T cells. Addition of recombinant IL-12 to cultures of
curcumin-pretreated macrophages and CD4+ T cells restored IFN-gamma production
in CD4+ T cells. 4 The in vivo administration of curcumin resulted in the
inhibition of IL-12 production by macrophages stimulated in vitro with either
LPS or HKL, leading to the inhibition of Th1 cytokine profile (decreased
IFN-gamma and increased IL-4 production) in CD4+ T cells. 5 These findings
suggest that curcumin may inhibit Th1 cytokine profile in CD4+ T cells by
suppressing IL-12 production in macrophages, and points to a possible
therapeutic use of curcumin in the Th1-mediated immune diseases.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10510448 [PubMed - indexed for MEDLINE]

249: FEBS Lett. 1999 Aug 6;456(2):311-4.

Curcumin mediated apoptosis in AK-5 tumor cells involves the production of
reactive oxygen intermediates.

Bhaumik S, Anjum R, Rangaraj N, Pardhasaradhi BV, Khar A.

Centre for Cellular and Molecular Biology, Hyderabad, India.

Curcumin, the active ingredient of the rhizome of Curcuma longa has
anti-inflammatory, antioxidant and antiproliferative activities. Although its
precise mode of action remains elusive, studies have shown that chemopreventive
action of curcumin might be due to its ability to induce apoptosis in cancer
cells. Curcumin was shown to be responsible for the inhibition of AK-5 tumor (a
rat histiocytoma) growth by inducing apoptosis in AK-5 tumor cells via caspase
activation. This study was designed to investigate the mechanism leading to the
induction of apoptosis in AK-5 tumor cells. Curcumin treatment resulted in the
hyperproduction of reactive oxygen species (ROS), loss of mitochondrial membrane
potential (delta psi(m)) and cytochrome c release to the cytosol, with the
concomitant exposure of phosphatidylserine (PS) residues on the cell surface.
This study suggests redox signalling and caspase activation as the mechanisms
responsible for the induction of curcumin mediated apoptosis in AK-5 tumor
cells.

PMID: 10456330 [PubMed - indexed for MEDLINE]

250: Phytother Res. 1999 Jun;13(4):318-22.

Efficacy of curcumin in the management of chronic anterior uveitis.

Lal B, Kapoor AK, Asthana OP, Agrawal PK, Prasad R, Kumar P, Srimal RC.

Department of Ophthalmology, K.G. Medical College, Lucknow, India.

Curcumin, obtained from rhizomes of Curcuma longa, was administered orally to
patients suffering from chronic anterior uveitis (CAU) at a dose of 375 mg three
times a day for 12 weeks. Of 53 patients enrolled, 32 completed the 12-week
study. They were divided into two groups: one group of 18 patients received
curcumin alone, whereas the other group of 14 patients, who had a strong PPD
reaction, in addition received antitubercular treatment. The patients in both
the groups started improving after 2 weeks of treatment. All the patients who
received curcumin alone improved, whereas the group receiving antitubercular
therapy along with curcumin had a response rate of 86%. Follow up of all the
patients for the next 3 years indicated a recurrence rate of 55% in the first
group and of 36% in the second group. Four of 18 (22%) patients in the first
group and 3 of 14 patients (21%) in the second group lost their vision in the
follow up period due to various complications in the eyes, e.g. vitritis,
macular oedema, central venous block, cataract formation, glaucomatous optic
nerve damage etc. None of the patients reported any side effect of the drug. The
efficacy of curcumin and recurrences following treatment are comparable to
corticosteroid therapy which is presently the only available standard treatment
for this disease. The lack of side effects with curcumin is its greatest
advantage compared with corticosteroids. A double blind multi-centric clinical
trial with this drug in CAU is highly desirable to further validate the results
of the present study.

Publication Types:
Clinical Trial

PMID: 10404539 [PubMed - indexed for MEDLINE]

251: Altern Med Rev. 1999 Jun;4(3):178-88.

A review of plants used in the treatment of liver disease: part two.

Luper S.

Southwest College of Naturopathic Medicine: 2140 East Broadway Rd. Tempe, AZ
85282, USA. [email protected]

Botanical medicines have been used traditionally by herbalists and indigenous
healers worldwide for the prevention and treatment of liver disease. Clinical
research in this century has confirmed the efficacy of several plants in the
treatment of liver disease, while basic scientific research has uncovered the
mechanisms by which some plants provide their therapeutic effects. This article
is Part Two in a review of botanicals used in the treatment of liver disease.
Curcuma longa (turmeric), Camellia sinensis (green tea), and Glycyrrhiza glabra
(licorice) are reviewed in this installment. Silybum marianum (milk thistle) and
Picrorhiza kurroa (kutkin) were reviewed in Part One.

Publication Types:
Review

PMID: 10383482 [PubMed - indexed for MEDLINE]

252: Phytother Res. 1999 May;13(3):231-2.

Investigation of the effects of selected medicinal plants on experimental
thrombosis.

Olajide OA.

Department of Pharmacology and Therapeutics, College of Medicine, University of
Ibadan, Nigeria.

Six medicinal plants indigenous to Africa were evaluated for their activity on
experimental thrombosis in mice. Of the plants screened, the extract of
Commiphora molmol exhibited the strongest antithrombotic activity, while the
extract of Ageratum conyzoides showed no marked activity. This study established
the antithrombotic effect of the extracts of Azadiractha indica, Bridelia
ferruginea, Commiphora molmol, Garcinia kola and Curcuma longa.

PMID: 10353165 [PubMed - indexed for MEDLINE]

253: Pharmacol Res. 1999 Mar;39(3):175-9.

Dietary curcumin with cisplatin administration modulates tumour marker indices
in experimental fibrosarcoma.

Navis I, Sriganth P, Premalatha B.

Departmant of Madical Biochemistry, University of Madras, Taramani Campus,
Chennai, 600 113, India.

Curcumin, the active constituent of Curcuma longa, which itself possesses
antitumour activity against experimental tumours, enhances the antitumour effect
of the widely used anticancer drug cisplatin, when used in combination against
fibrosarcoma. Tumour marker enzymes such as aminotransferases, lactate
dehydrogenase, gamma-glutamyl transpeptidase, alkaline phosphatase,
5'-nucleotidase were analysed in liver and kidney homogenates of experimental
rats. All these enzyme activities were markedly increased in tumour bearing
animals. On cisplatin administration, the enzyme levels were decreased but not
to near normal values. Curcumin, when treated along with cisplatin brought back
the enzyme levels to near the control values. Thus curcumin and cisplatin
combination may be worth trying against tumours like fibrosarcoma. Copyright
1999 The Italian Pharmacological Society.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10094841 [PubMed - indexed for MEDLINE]

254: J Ethnopharmacol. 1999 Jan;64(1):1-7.

Modulation of radioresponse of glyoxalase system by curcumin.

Choudhary D, Chandra D, Kale RK.

School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.

Human beings have been exposed to radiation for many years. It is quite possible
that antioxidant phytochemicals consumed in their diet might be providing a
variable degree of radioprotection. However, their radiomodifying ability is not
well understood. In the present work, curcumin (diferuloyl methane), a
phytochemical present in the rhizome of Curcuma longa Linn. has been examined
for its radioprotective property using the glyoxalase system which is vital for
various biological functions. Curcumin (5, 25 and 50 mg/kg body weight) in olive
oil was given orally to Swiss albino male mice (7-8 weeks old) daily for 2 weeks
and irradiated with different doses of gamma-radiation (0-6 Gy) at 0.027 Gy per
second dose rate on last day of the treatment. The specific activities of
glyoxalase I and II were determined in the liver and spleen. The treatment of
curcumin prior to irradiation restored the specific activity of glyoxalase
system to almost the control level which was suggestive of the radioprotective
ability of curcumin. Free radical scavenging and electron/hydrogen donation are
probable attributes for the protective effect of curcumin.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10075116 [PubMed - indexed for MEDLINE]

255: FEBS Lett. 1999 Feb 19;445(1):165-8.

Antitumor activity of curcumin is mediated through the induction of apoptosis in
AK-5 tumor cells.

Khar A, Ali AM, Pardhasaradhi BV, Begum Z, Anjum R.

Centre for Cellular and Molecular Biology, Hyderabad, India. [email protected]

Curcumin, the yellow pigment of turmeric (Curcuma longa), used commonly as a
spice, has been shown to possess anticarcinogenic activity. Curcumin inhibited
AK-5 tumor growth and induced apoptosis in AK-5 cells. Curcumin induced
apoptosis is mediated through the activation of caspase-3, which is specifically
inhibited by the tetrapeptide Ac-DEVD-CHO. In addition, curcumin induced tumor
cell death is caused through the generation of reactive oxygen intermediates
which is inhibited by N-acetyl-L-cysteine. Our studies suggest that the
apoptotic process induced by curcumin is the mechanism mediating AK-5 tumor cell
death.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10069393 [PubMed - indexed for MEDLINE]

256: Cancer Res. 1999 Feb 1;59(3):597-601.

Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory
agent, during the promotion/progression stages of colon cancer.

Kawamori T, Lubet R, Steele VE, Kelloff GJ, Kaskey RB, Rao CV, Reddy BS.

Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla,
New York 10595, USA.

Curcumin, derived from the rhizome of Curcuma longa L. and having both
antioxidant and anti-inflammatory properties, inhibits chemically induced
carcinogenesis in the skin, forestomach, and colon when it is administered
during initiation and/or postinitiation stages. This study was designed to
investigate the chemopreventive action of curcumin when it is administered (late
in the premalignant stage) during the promotion/progression stage of colon
carcinogenesis in male F344 rats. We also studied the modulating effect of this
agent on apoptosis in the tumors. At 5 weeks of age, groups of male F344 rats
were fed a control diet containing no curcumin and an experimental AIN-76A diet
with 0.2% synthetically derived curcumin (purity, 99.9%). At 7 and 8 weeks of
age, rats intended for carcinogen treatment were given s.c. injections of
azoxymethane (AOM) at a dose rate of 15 mg/kg body weight per week. Animals
destined for the promotion/progression study received the AIN-76A control diet
for 14 weeks after the second AOM treatment and were then switched to diets
containing 0.2 and 0.6% curcumin. Premalignant lesions in the colon would have
developed by week 14 following AOM treatment. They continued to receive their
respective diets until 52 weeks after carcinogen treatment and were then
sacrificed. The results confirmed our earlier study in that administration of
0.2% curcumin during both the initiation and postinitiation periods
significantly inhibited colon tumorigenesis. In addition, administration of 0.2%
and of 0.6% of the synthetic curcumin in the diet during the
promotion/progression stage significantly suppressed the incidence and
multiplicity of noninvasive adenocarcinomas and also strongly inhibited the
multiplicity of invasive adenocarcinomas of the colon. The inhibition of
adenocarcinomas of the colon was, in fact, dose dependent. Administration of
curcumin to the rats during the initiation and postinitiation stages and
throughout the promotion/progression stage increased apoptosis in the colon
tumors as compared to colon tumors in the groups receiving AOM and the control
diet. Thus, chemopreventive activity of curcumin is observed when it is
administered prior to, during, and after carcinogen treatment as well as when it
is given only during the promotion/progression phase (starting late in
premalignant stage) of colon carcinogenesis.

Publication Types:
Research Support, U.S. Gov't, P.H.S.

PMID: 9973206 [PubMed - indexed for MEDLINE]

257: Lipids. 1998 Dec;33(12):1223-8.

Inhibition of lipoxygenase 1 by phosphatidylcholine micelles-bound curcumin.

Began G, Sudharshan E, Appu Rao AG.

Department of Protein Chemistry and Technology, Central Food Technological
Research Institute, Mysore, India.

Curcumin (diferuloyl methane) from rhizomes of Curcuma longa L. binds to
phosphatidylcholine (PC) micelles. The binding of curcumin with PC micelles was
followed by fluorescence measurements. Curcumin emits at 490 nm with an
excitation wavelength of 451 nm after binding to PC-mixed micelles stabilized
with deoxycholate. Curcumin in aqueous solution does not inhibit dioxygenation
of fatty acids by Lipoxygenase 1 (LOX1). But, when bound to PC micelles, it
inhibits the oxidation of fatty acids. The present study has shown that 8.6
microM of curcumin bound to the PC micelles is required for 50% inhibition of
linoleic acid peroxidation. Lineweaver-Burk plot analysis has indicated that
curcumin is a competitive inhibitor of LOX1 with Ki of 1.7 microM for linoleic
and 4.3 microM for arachidonic acids, respectively. Based on spectroscopic
measurements, we conclude that the inhibition of LOX1 activity by curcumin can
be due to binding to active center iron and curcumin after binding to the PC
micelles acts as an inhibitor of LOX1.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9930409 [PubMed - indexed for MEDLINE]

258: Wound Repair Regen. 1998 Mar-Apr;6(2):167-77.

Enhancement of wound healing by curcumin in animals.

Sidhu GS, Singh AK, Thaloor D, Banaudha KK, Patnaik GK, Srimal RC, Maheshwari
RK.

Center for Combat Casualty and Life Sustainment Research, Department of
Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD,
USA.

Tissue repair and wound healing are complex processes that involve inflammation,
granulation, and remodeling of the tissue. In this study, we evaluated the in
vivo effects of curcumin (difeurloylmethane), a natural product obtained from
the rhizomes of Curcuma longa on wound healing in rats and guinea pigs. We
observed faster wound closure of punch wounds in curcumin-treated animals in
comparison with untreated controls. Biopsies of the wound showed
reepithelialization of the epidermis and increased migration of various cells
including myofibroblasts, fibroblasts, and macrophages in the wound bed.
Multiple areas within the dermis showed extensive neovascularization, and
Masson's Trichrome staining showed greater collagen deposition in
curcumin-treated wounds. Immunohistochemical localization of transforming growth
factor-beta1 showed an increase in curcumin-treated wounds as compared with
untreated wounds. In situ hybridization and polymerase chain reaction analysis
also showed an increase in the mRNA transcripts of transforming growth
factor-beta1 and fibronectin in curcumin-treated wounds. Because transforming
growth factor-beta1 is known to enhance wound healing, it may be possible that
transforming growth factor-beta1 plays an important role in the enhancement of
wound healing by curcumin.

Publication Types:
Comparative Study
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 9776860 [PubMed - indexed for MEDLINE]

259: Carcinogenesis. 1998 Aug;19(8):1377-81.

Suppression of mouse skin tumor promotion and induction of apoptosis in HL-60
cells by Alpinia oxyphylla Miquel (Zingiberaceae).

Lee E, Park KK, Lee JM, Chun KS, Kang JY, Lee SS, Surh YJ.

College of Pharmacy, Seoul National University, Korea.

There have been considerable efforts to search for naturally occurring
substances for the intervention of carcinogenesis. Many components from dietary
or medicinal plants have been identified that possess substantial
chemopreventive properties. An example is curcumin (Curcuma longa Linn.,
Zingiberaceae), which has been shown to inhibit tumor promotion in experimental
carcinogenesis. Alpinia oxyphylla Miquel, another plant of the ginger family
used in oriental herbal medicine, contains diarylheptanoids whose structures are
analogous to that of curcumin. In the present study, we have tested A.oxyphylla
for its ability to suppress tumor promotion. Thus, topical application of the
methanolic extract of dried fruits of A.oxyphylla significantly ameliorated
12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumor promotion as well
as ear edema in female ICR mice. In another study, treatment of HL-60 cells with
the methanolic extract of A.oxyphylla significantly reduced the viability of the
cells and also inhibited DNA synthesis. Microscopic examination of the treated
cells showed characteristic morphology of apoptosis. Furthermore, cells treated
with the extract of A.oxyphylla exhibited internucleosomal DNA fragmentation in
time- and concentration-dependent manners. TPA-stimulated generation of
superoxide anion in differentiated HL-60 cells was also blunted by A.oxyphylla.
Taken together, these findings suggest that A.oxyphylla possesses potential
chemopreventive and antitumorigenic activities.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9744532 [PubMed - indexed for MEDLINE]

260: Indian J Exp Biol. 1998 Jun;36(6):573-7.

Protective effect of turmeric (Curcuma longa L.) extract on carbon
tetrachloride-induced liver damage in rats.

Deshpande UR, Gadre SG, Raste AS, Pillai D, Bhide SV, Samuel AM.

Radiation Medicine Centre (BARC), Bombay, India.

The protective effect of tumeric extract (TE) in diet on CCl4-treated rats was
studied. Rats were divided into 5 groups: (1) untreated, (2) CCl4 treated, (3)
pre-TE for 2 weeks followed by CCl4, (4) TE + CCl4 given concurrently and (5) 5%
TE as positive control. The serum levels of bilirubin, cholesterol, aspartate
aminotransferase, (AST), alanine amino transferase (AST), (ALT) and alkaline
phosphatase were estimated after 1, 2 and 3 months. CCl4 caused a maximum
increase (2-3-fold in all the above parameters. As compared to CCl4 group, a
short pre-treatment of TE showed reduction in cholesterol, bilirubin, AST, ALT
and alkaline phosphatase activity whereas concurrent treatment of TE + CCl4
reduced to a greater extent the levels of all parameters except ALT. To
conclude, concurrent treatment of TE gave significant protection against CCl4
though the values did not reach the normal levels.

PMID: 9731471 [PubMed - indexed for MEDLINE]

261: Biofactors. 1998;8(1-2):51-7.

An ethanolic-aqueous extract of Curcuma longa decreases the susceptibility of
liver microsomes and mitochondria to lipid peroxidation in atherosclerotic
rabbits.

Quiles JL, Aguilera C, Mesa MD, Ramirez-Tortosa MC, Baro L, Gil A.

Department of Physiology, University of Granada, Spain.

Atherosclerosis is characterized by oxidative damage which affects lipoproteins,
the walls of blood vessels and subcellular membranes. This study evaluates the
antioxidant capacity of a Curcuma longa extract on the lipid peroxidation of
liver mitochondria and microsome membranes in atherosclerotic rabbits. Male
rabbits fed a 3% (w/w) lard and 1.3% (w/w) cholesterol diet were randomly
assigned to three groups. Two groups were treated with different dosages of a
turmeric extract (A and B) and the third group (control) with a curcumin-free
solution. Basal and in vitro 2,2'-azobis (2-amidinopropane) dihydrochloride
(AAPH)-induced hydroperoxide and TBARS productions in liver mitochondria and
microsomes were analyzed. Group A had the lowest concentration of mitochondrial
hydroperoxides. In microsomes, the basal hydroperoxide levels were similar in
all groups but, after the induction of oxidation, group C registered the highest
value; TBARS production followed the same trend in mitochondria. These findings
suggest that active compounds in curcuma extract may be protective in preventing
lipoperoxidation of subcellular membranes in a dosage-dependent manner.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9699009 [PubMed - indexed for MEDLINE]

262: Int J Biochem Cell Biol. 1998 Apr;30(4):445-56.

Mechanisms of anticarcinogenic properties of curcumin: the effect of curcumin on
glutathione linked detoxification enzymes in rat liver.

Piper JT, Singhal SS, Salameh MS, Torman RT, Awasthi YC, Awasthi S.

Department of Internal Medicine, University of Texas Medical Branch, Galveston
77555-1067, USA.

Curcumin, an antioxidant isolated from turmeric (curcuma longa), has been shown
to attenuate chemical carcinogenesis in rodents. Previous studies have shown
that curcumin causes an increase in glutathione S-transferase (GST) activity in
rodent liver which may contribute to its anti-cancer and anti-inflammatory
activities. Since the effects of curcumin on specific GST isozymes and other
glutathione (GSH)-linked enzymes are incompletely defined, we have examined in
the present studies the effect of curcumin on hepatic non-protein sulfhydryls
and GSH-linked enzymes in male Sprague-Dawley rats. When rats were fed curcumin
at doses from 1 to 500 mg kg-1 body weight daily for 14 days, the induction of
hepatic GST activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was found to be
biphasic, with maximal induction of about 1.5 fold at the 25 to 50 mg kg-1 body
weight dosage. At higher doses, a decrease was observed in the activity and in
the rats treated with 500 mg kg-1 curcumin this activity was below the levels
observed in controls. In contrast, GST activity towards 4-hydroxynonenal (4-HNE)
increased in a saturable, dose dependent manner. Western-blot analyses of liver
cytosols revealed that curcumin caused a dose dependent induction of rGST 8-8,
an isozyme which is known to display the highest activity towards 4-HNE, a
highly toxic product of lipid peroxidation. Glutathione peroxidase (GPx)
activity towards cumene hydroperoxide in liver homogenate was also found to be
increased in a saturable manner with respect to curcumin dose. Our results
suggest that induction of enzymes involved in the detoxification of the
electrophilic products of lipid peroxidation may contribute to the
anti-inflammatory and anti-cancer activities of curcumin.

Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

PMID: 9675878 [PubMed - indexed for MEDLINE]

263: Prev Vet Med. 1998 Jun 1;35(3):149-63.

Ethnoveterinary medicines used for ruminants in Trinidad and Tobago.

Lans C, Brown G.

School of Veterinary Medicine, University of the West Indies, St. Augustine,
Trinidad and Tobago.

Ethnoveterinary research was conducted in Trinidad and Tobago in 1995, in order
to document existing ethnoveterinary practices. This paper describes 20
medicinal plants used to treat ruminants. The main plants used were Azadirachta
indica and Curcuma longa. Medicinal plants were used predominantly for
endoparasites, internal and external injuries and pregnancy-related conditions.
A 4-stage process was used to conduct the research and document the
ethnoveterinary practices. This documentation could provide a foundation for the
further scientific study and verification of those practices which merit such
study.

PMID: 9658442 [PubMed - indexed for MEDLINE]

264: Life Sci. 1998;62(25):2349-58.

Effects of curcumin on P-glycoprotein in primary cultures of rat hepatocytes.

Romiti N, Tongiani R, Cervelli F, Chieli E.

Dipartimento di Biomedicina Sperimentale, Universita degli Studi di Pisa, Scuola
Medica, Italy.

Curcumin is a natural phenolic compound found in the rhizomes of Curcuma longa
and endowed with beneficial biological activities including antioxidant,
anticarcinogenic and hepatoprotective effects. In this study curcumin was tested
for its potential ability to interact in vitro with hepatic P-glycoprotein
(Pgp), in a model system represented by primary cultures of rat hepatocytes, in
which spontaneous overexpression of multidrug resistance (mdr) genes occurs. In
both freshly-plated hepatocytes, containing low levels of Pgp, and 72
hour-cultured hepatocytes, containing high levels of Pgp, the Rhodamine-123
(R-123) efflux, which represents a specific functional test for Pgp-mediated
transport, was inhibited by curcumin in a dose-dependent manner. Western blot
analysis showed that 25microM curcumin, when included in the culture medium
throughout the experimental observation (72 hours), was able to significantly
lower the increase of mAb C219-immunoreactive protein spontaneously occurring in
the cells during culture. Curcumin, at doses ranging from 50 to 150microM was
cytotoxic for freshly-plated hepatocytes, as shown by the strong decrease in the
cell ability to exclude trypan blue 24 hours later, but it was significantly
less cytotoxic when added to 24 or 48 hour-cultured cells. The resistance to
curcumin, progressively acquired by cells during culture, was significantly
reduced by high concentrations of dexamethasone (DEX) or dimethyl-sulfoxide
(DMSO), culture conditions known to inhibit the spontaneous overexpression of
Pgp. In addition, in a concentration-dependent manner, verapamil reverted
curcumin resistance in Pgp overexpressing hepatocytes. In photoaffinity labeling
studies, curcumin competed with azidopine for binding to Pgp, suggesting a
direct interaction with glycoprotein. These results suggest that curcumin is
able to modulate in vitro both expression and function of hepatic Pgp and
support the hypothesis that curcumin, a chemopreventive phytochemical, could
reveal itself also as a compound endowed with chemosensitizing properties on mdr
phenotype.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9651124 [PubMed - indexed for MEDLINE]

265: Planta Med. 1998 May;64(4):353-6.

Influence of piperine on the pharmacokinetics of curcumin in animals and human
volunteers.

Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS.

Department of Pharmacology, St. John's Medical College, Bangalore, India.

The medicinal properties of curcumin obtained from Curcuma longa L. cannot be
utilised because of poor bioavailability due to its rapid metabolism in the
liver and intestinal wall. In this study, the effect of combining piperine, a
known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the
bioavailability of curcumin in rats and healthy human volunteers. When curcumin
was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were
achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg
increased the serum concentration of curcumin for a short period of 1-2 h post
drug. Time to maximum was significantly increased (P < 0.02) while elimination
half life and clearance significantly decreased (P < 0.02), and the
bioavailability was increased by 154%. On the other hand in humans after a dose
of 2 g curcumin alone, serum levels were either undetectable or very low.
Concomitant administration of piperine 20 mg produced much higher concentrations
from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the
increase in bioavailability was 2000%. The study shows that in the dosages used,
piperine enhances the serum concentration, extent of absorption and
bioavailability of curcumin in both rats and humans with no adverse effects.

Publication Types:
Clinical Trial

PMID: 9619120 [PubMed - indexed for MEDLINE]

266: J Nat Prod. 1998 Apr;61(4):542-5.

Novel bioactivities of Curcuma longa constituents.

Roth GN, Chandra A, Nair MG.

Department of Horticulture, Michigan State University, East Lansing 48823, USA.

Bioassay-directed fractionation of ethyl acetate extract from Curcuma longa
Linn. rhizomes yielded three curcuminoids, which displayed topoisomerase I and
II enzyme inhibition activity. Curcumin III (3) was the most active curcuminoid,
inhibiting topoisomerase at 25 micrograms mL-1. Curcumin I (1) and curcumin II
(2) inhibited the topoisomerases at 50 micrograms mL-1. Fractionation of the
volatile oil from the rhizomes afforded ar-turmerone (4), which displayed
mosquitocidal activity with an LD100 of 50 micrograms mL-1 on Aedes aegyptii
larvae. Bioassay-directed fractionation of hexane extract from the turmeric
leaves yielded labda-8(17),12-diene-15,16 dial (5) with antifungal activity
against Candida albicans at 1 micrograms mL-1 and inhibited the growth of
Candida kruseii and Candida parapsilosis at 25 micrograms mL-1. In addition, 5
displayed 100% mosquitocidal activity on A. aegyptii larvae at 10 micrograms
mL-1.

PMID: 9584408 [PubMed - indexed for MEDLINE]

267: Mol Cell Biochem. 1998 Apr;181(1-2):87-96.

Amelioration of renal lesions associated with diabetes by dietary curcumin in
streptozotocin diabetic rats.

Suresh Babu P, Srinivasan K.

Department of Biochemistry and Nutrition, Central Food Technological Research
Institute, Mysore, India.

Curcumin, the coloring principle of the commonly used spice turmeric (Curcuma
longa) was fed at 0.5% in the diet to streptozotocin-induced diabetic Wistar
rats for 8 weeks. Renal damage was assessed by the amount of proteins excreted
in the urine and the extent of leaching of renal tubular enzymes: NAG, LDH,
AsAT, AlAT, alkaline and acid phosphatases. The integrity of kidney was assessed
by measuring the activities of several key enzymes of the renal tissue:
glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, and LDH (Carbohydrate
metabolism), aldose reductase and sorbitol dehydrogenase (polyol pathway),
transaminases, ATPases and membrane PUFA/SFA ratio (membrane integrity). Data on
enzymuria, albuminuria, activity of kidney ATPases and fatty acid composition of
renal membranes in diabetic condition suggested that dietary curcumin brought
about significant beneficial modulation of the progression of renal lesions in
diabetes. These findings were also corroborated by histological examination of
kidney sections. It is inferred that this beneficial ameliorating influence of
dietary curcumin on diabetic nephropathy is possibly mediated through its
ability to lower blood cholesterol levels.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9562245 [PubMed - indexed for MEDLINE]

268: Res Virol. 1998 Jan-Feb;149(1):43-52.

Curcumin and curcumin derivatives inhibit Tat-mediated transactivation of type 1
human immunodeficiency virus long terminal repeat.

Barthelemy S, Vergnes L, Moynier M, Guyot D, Labidalle S, Bahraoui E.

Laboratoire de Synthese, Physico-Chimie et Radiobiologie, Faculte de Pharmacie,
Toulouse, France.

The transcription of HIV1 provirus is regulated by both cellular and viral
factors. Various evidence suggests that Tat protein secreted by HIV1-infected
cells may have additional action in the pathogenesis of AIDS because of its
ability to also be taken up by non-infected cells. Curcumin [diferuloylmethane
or 1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is the yellow
pigment in turmeric Curcuma longa (Linn). It exhibits a variety of
pharmacological effects including antiinflammatory and antiretroviral
activities. Here, we demonstrated that curcumin used at 10 to 100 nM inhibited
Tat transactivation of HIV1-LTR lacZ by 70 to 80% in HeLa cells. In order to
develop more efficient curcumin derivatives, we synthesized and tested in the
same experimental system the inhibitory activity of reduced curcumin (C1), which
lacks the spatial structure of curcumin; allyl-curcumin (C2), which possesses a
condensed allyl derivative on curcumin that plays the role of metal chelator;
and tocopheryl-curcumin (C3), which enhances the antioxidant activity of the
molecule. Results obtained with C1, C2 and C3 curcumin derivatives showed a
significant inhibition (70 to 85%) of Tat transactivation. Despite the fact that
tocopheryl-curcumin (C3) failed to scavenge O2.-, this curcumin derivative
exhibited the most activity; 70% inhibition was obtained at 1 nM, while only 35%
inhibition was obtained with the curcumin.

PMID: 9561563 [PubMed - indexed for MEDLINE]

269: J Lab Clin Med. 1997 Dec;130(6):656.

Comment on:
J Lab Clin Med. 1997 Dec;130(6):576-84.

Curcuma longa: culinary turmeric.

Hammerschmidt DE.

Publication Types:
Comment

PMID: 9422340 [PubMed - indexed for MEDLINE]

270: J Lab Clin Med. 1997 Dec;130(6):576-84.

Comment in:
J Lab Clin Med. 1997 Dec;130(6):656.

Curcumin, a natural plant phenolic food additive, inhibits cell proliferation
and induces cell cycle changes in colon adenocarcinoma cell lines by a
prostaglandin-independent pathway.

Hanif R, Qiao L, Shiff SJ, Rigas B.

Department of Medicine, Cornell University Medical College, New York, New York,
USA.

Curcumin, the active ingredient of the rhizome of the plant turmeric (Curcuma
longa Linn), a commonly used spice, prevents cancer in animal tumor models. Its
mechanism of action is unknown; curcumin may act by inhibiting arachidonic acid
metabolism. To explore the mechanism of curcumin's chemopreventive effect, we
studied its role in proliferation and apoptosis in the HT-29 and HCT-15 human
colon cancer cell lines. Curcumin dose-dependently reduced the proliferation
rate of both cell lines, causing a 96% decrease by 48 hours. No apoptosis was
detected. The antiproliferative effect was preceded by accumulation of the cells
in the G2/M phase of cell cycle. The effect of curcumin was similar in both cell
lines, which, however, differ in their ability to produce prostaglandins. We
conclude that curcumin inhibits colon cancer cell proliferation in vitro mainly
by accumulating cells in the G2/M phase and that this effect is independent of
its ability to inhibit prostaglandin synthesis. The role of curcumin's
antiproliferative effect in human colon cancer remains to be established.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9422331 [PubMed - indexed for MEDLINE]

271: FEBS Lett. 1997 Nov 10;417(2):196-8.

Inhibitory effect on curcumin on mammalian phospholipase D activity.

Yamamoto H, Hanada K, Kawasaki K, Nishijima M.

Department of Biochemistry and Cell Biology, National Institute of Infectious
Diseases, Toyama, Tokyo, Japan.

Curcumin, the major yellow pigment of turmeric (Curcuma longa), has strong
anti-carcinogenic and anti-inflammatory activities. We examined the effects of
curcumin on enzyme activities of the following phospholipases in a cell-free
system: G protein-mediated phospholipase D (PLD), phosphatidylinositol-specific
phospholipase C, and phospholipase A2 from mouse macrophage-like cell line
J774.1 cells, sphingomyelinase from bovine brain, and
phosphatidylcholine-phospholipase C from Bacillus cereus. Curcumin inhibited
several types of phospholipases, most effectively PLD among those tested. It
also inhibited 12-O-tetradecanoylphorbol-13-acetate-induced PLD activation in
intact J774.1 cells in a dose-dependent manner. These results suggest that the
anti-inflammatory and anti-carcinogenic action of curcumin is partly due to the
inhibition of PLD.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9395294 [PubMed - indexed for MEDLINE]

272: Biochem Pharmacol. 1997 Oct 15;54(8):899-907.

Inhibition of proliferation and apoptosis of human and rat T lymphocytes by
curcumin, a curry pigment.

Sikora E, Bielak-Zmijewska A, Piwocka K, Skierski J, Radziszewska E.

Department of Cellular Biochemistry, Nencki Institute of Experimental Biology,
Warsaw, Poland. [email protected]

Curcumin (diferuoylmethane), the yellow pigment in the rhizome of tumeric
(Curcuma longa), an ingredient of curry spice, is known to exhibit a variety of
pharmacological effects including antitumor, antiinflammatory, and
antiinfectious activities. Although its precise mode of action remains elusive,
curcumin has been shown to suppress the activity of the AP-1 transcription
factor in cells stimulated to proliferate. In this study, we observed that
curcumin (50 microM) inhibited proliferation of rat thymocytes stimulated with
concanavalin A (Con A) as well as that of human Jurkat lymphoblastoid cells in
the logarithmic growth phase. The pigment also inhibited apoptosis in
dexamethasone-treated rat thymocytes and in UV-irradiated Jurkat cells as judged
by DNA ladder formation, cellular morphological changes, and flow cytometry
analysis. The inhibition of apoptosis by curcumin in rat thymocytes was
accompanied by partial suppression of AP-1 activity. Complete suppression of
AP-1 activity was observed in Con A-treated, proliferating thymocytes. The
capacity of curcumin to inhibit both cell growth and death strongly implies that
these two biological processes share a common pathway at some point and that
curcumin affects a common step, presumably involving a modulation of the AP-1
transcription factor.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9354590 [PubMed - indexed for MEDLINE]

273: Zhong Yao Cai. 1997 Jul;20(7):345-50.

[Technological study on the supercritical-CO2 fluid extraction of Curcuma longa
oils]

[Article in Chinese]

Ge F, Shi Q, Tan X, Li Z, Jing X.

Guangzhou Pharmaceutical Industrial Research Institute, Guangzhou 510240.

This paper first reports technological study on the extraction of Curcuma longa
oils by supercritical-CO2 fluid, mainly studies the influence of pressure,
temperature, flow rate of CO2 and time on the yield of the oils, determines
optimum technology of extracting the oils, analyzes chemical constituents
extracted, compares the oils from SFE-CO2 and SD technology, studies industrial
test on the SF-CO2 extraction. The results shows pressure and temperature are
more important factors of influence; the optimum technological condition is the
extracted pressure 25 MPa and temperature 45 degrees C, isolated pressure I 12.5
MPa and temperature I 60 degrees C, isolated pressure II 6MPa and temperature II
38 degrees C, CO2 flow rate 9 Kg/Kg.h, and extracted time 2 h; the constituents
from SFE-CO2 and SD methods are identical, but their content has some
difference; SFE-CO2 technology is better than that of SD, which is high yield
shorter time, etc.; the industrial production of the oils with SFE-CO2 method is
available.

Publication Types:
English Abstract

PMID: 12572431 [PubMed - indexed for MEDLINE]

274: Cancer Lett. 1997 Jun 24;116(2):197-203.

Inhibitory effect of dietary curcumin on skin carcinogenesis in mice.

Limtrakul P, Lipigorngoson S, Namwong O, Apisariyakul A, Dunn FW.

Department of Biochemistry, Faculty of Medicine, Chiang Mai University,
Thailand.

Laboratory animal model studies have suggested that curcumin may play an
important role in inhibiting the process of carcinogenesis. Curcumin, the yellow
pigment that is obtained from rhizomes of the plant Curcuma longa Linn (Family
Zingiberaceae), is commonly used as a spice and food coloring agent. The present
study was designed to investigate the chemopreventive action of dietary curcumin
on 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and
12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation in male
Swiss ablino mice. At 6 weeks of age, groups of animals were fed the standard
(modified AIN-76 A) diet or a diet containing 1% curcumin. At 8 weeks of age,
all animals, except those in the vehicle (acetone)-treated groups, received 100
microg of DMBA dissolved in 100 microl of acetone in a single application to the
skin of the back. From 1 week after DMBA application, tumor promoter (2.5 microg
of TPA dissolved in 100 microl of acetone) was applied to the same areas on
mouse skin twice a week for 26 weeks. All groups continued on their respective
dietary regimen until the termination of the experiment. The results indicate
that dietary administration of curcumin significantly inhibited the number of
tumors per mouse (P < 0.05) and the tumor volume (P < 0.01). The percentage of
tumor-bearing mice tended to be lower in the mice on the curcumin diet than
those on the standard diet. There was no difference in growth between mice of
the standard and 1% curcumin groups. The results indicate the safety and the
anti-carcinogenic effect of curcumin in mice.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9215864 [PubMed - indexed for MEDLINE]

275: Planta Med. 1997 Jun;63(3):265-6.

Protective effect of curcuminoids on epidermal skin cells under free oxygen
radical stress.

Bonte F, Noel-Hudson MS, Wepierre J, Meybeck A.

Curcuminoids from Curcuma longa L. (Zingiberaceae) protected normal human
keratinocytes from hypoxanthine/ xanthine oxidase injury. Since curcuminoids
synergistically inhibited nitroblue tetrazolium reduction, a decrease in
superoxide radical formation leading to lower levels of cytotoxic hydrogen
peroxide was proposed as an explanation for this protective effect.

Publication Types:
Letter

PMID: 9225611 [PubMed - indexed for MEDLINE]

276: Anticancer Drugs. 1997 Jun;8(5):470-81.

Antiproliferative effect of curcumin (diferuloylmethane) against human breast
tumor cell lines.

Mehta K, Pantazis P, McQueen T, Aggarwal BB.

Department of Bioimmunotherapy, The University of Texas MD Anderson Cancer
Center, Houston 77030, USA.

Pharmacologically safe compounds that can inhibit the proliferation of tumor
cells have potential as anticancer agents. Curcumin, a diferuloylmethane, is a
major active component of the food flavor turmeric (Curcuma longa) that exhibits
anticarcinogenic properties in vivo. In vitro, it suppressed c-jun/Ap-1 and
NF-kappaB activation and type 1 human immunodeficiency virus long-terminal
repeat-directed gene expression. We examined the antiproliferative effects of
curcumin against several breast tumor cell lines, including hormone-dependent
and -independent and multidrug-resistant (MDR) lines. Cell growth inhibition was
monitored by [3H]thymidine incorporation, Trypan blue exclusion, crystal violet
dye uptake and flow cytometry. All the cell lines tested, including the
MDR-positive ones, were highly sensitive to curcumin. The growth inhibitory
effect of curcumin was time- and dose-dependent, and correlated with its
inhibition of ornithine decarboxylase activity. Curcumin preferentially arrested
cells in the G2/S phase of the cell cycle. Curcumin-induced cell death was
neither due to apoptosis nor to any significant change in the expression of
apoptosis-related genes, including Bcl-2, p53, cyclin B and transglutaminase.
Overall our results suggest that curcumin is a potent antiproliferative agent
for breast tumor cells and may have potential as an anticancer agent.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9215611 [PubMed - indexed for MEDLINE]

277: Cancer Lett. 1997 May 19;115(2):129-33.

Protective effect of food additives on aflatoxin-induced mutagenicity and
hepatocarcinogenicity.

Soni KB, Lahiri M, Chackradeo P, Bhide SV, Kuttan R.

Amala Cancer Research Centre, Kerala State, India.

Food additives such as turmeric (Curcuma longa), and active ingredient curcumin
(diferuloyl methane), asafoetida (flavouring agent), butylated hydroxyanisole
(BHA), butylated hydroxytoluene (BHT) and ellagic acid were found to inhibit the
mutagenesis induced by aflatoxin B1 (AFB1) (0.5 microg/plate) in Salmonella
tester strains TA 98 and TA 100. Turmeric and curcumin, which were the most
active, inhibited mutation frequency by more than 80% at concentrations of 2
microg/plate. Other food additives were also significantly effective. Dietary
administration of turmeric (0.05%), garlic (0.25%), curcumin and ellagic acid
(0.005% each) to rats significantly reduced the number of gammaglutamyl
transpeptidase-positive foci induced by AFB1 which is considered as the
precursor of hepatocellular neoplasm. These results indicate the usefulness of
antioxidant food additives in ameliorating aflatoxin-induced mutagenicity and
carcinogenicity.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9149115 [PubMed - indexed for MEDLINE]

278: Biochem Biophys Res Commun. 1997 Apr 28;233(3):692-6.

Curcumin and genistein, plant natural products, show synergistic inhibitory
effects on the growth of human breast cancer MCF-7 cells induced by estrogenic
pesticides.

Verma SP, Salamone E, Goldin B.

Department of Community Health. Tufts University School of Medicine, Boston,
Massachusetts 02111, USA.

Curcumin and genistein are two natural products of plants obtained from Curcuma
longa Linn (turmeric) and soybeans, respectively. Both compounds when present at
micromolar concentrations are able to inhibit the growth of estrogen-positive
human breast MCF-7 cells induced individually or by a mixture of the pesticides
endosulfane, DDT and chlordane or 17-beta estradiol. When curcumin and genistein
were added together to MCF-7 cells, a synergistic effect resulting in a total
inhibition of the induction of MCF-7 cells by the highly estrogenic activity of
endosulfane/chlordane/DDT mixtures was noted. These data suggest that the
combination of curcumin and genistein in the diet have the potential to reduce
the proliferation of estrogen-positive cells by mixtures of pesticides or
17-beta estradiol. Since it is difficult to remove pesticides completely from
the environment or the diet and since both turmeric and soybeans are not toxic
to humans, their inclusion in the diet in order to prevent hormone related
cancers deserves consideration.

Publication Types:
Research Support, U.S. Gov't, P.H.S.

PMID: 9168916 [PubMed - indexed for MEDLINE]

279: Zhongguo Zhong Yao Za Zhi. 1997 Mar;22(3):145-7, 190-1.

[Optimal high-yield agronomic measures for Curcuma longa L]

[Article in Chinese]

Li L, Qin S, Liao G, Fang Q, Yang S.

Sichan Institute of Chinese Materia Medica, Chongqing.

Regression method of orthogonal conic substitution with factors was employed to
build up a tuber yield simulation model. Three main measures (sowing time, plant
population, application rate of fertilizer) affecting the tuber yield were
analyzed by the mathematical model of three unknown second order orthogonal
rotative regression. The optimal agronomic measures were obtained. The results
indicate that sowing time and plant population play a important role in raising
the tuber yield. Sowing time is clearly interrelated with plant population, and
likewise, plant population application rate of fertilizer.

Publication Types:
English Abstract

PMID: 10743182 [PubMed - indexed for MEDLINE]

280: Zhongguo Zhong Yao Za Zhi. 1997 Feb;22(2):77-8, 126.

[Effect of cultivating measures on the tuber yield of Curcuma longa L.]

[Article in Chinese]

Li L, Qin S, Yang H.

Sichuan Institute of Chinese Materia Medica, Chongqing.

The effect of cultivating measures on the tuber yield of Curcuma longa was
observed. dibble planting has been proved move effective in raising the tuber
yield than drill culture, and the dibble planting quantity has no effect on the
tuber. The rational producing area, soil, seed tuber and so on were selected
according to the experiments.

Publication Types:
English Abstract

PMID: 10743196 [PubMed - indexed for MEDLINE]

281: J Cell Biochem Suppl. 1997;27:26-34.

Inhibitory effects of curcumin on tumorigenesis in mice.

Huang MT, Newmark HL, Frenkel K.

Department of Chemical Biology, College of Pharmacy, Rutgers-State University of
New Jersey, Piscataway, NJ 08854-8020, USA.

Curcumin (diferuloylmethane), the naturally occurring yellow pigment in turmeric
and curry, is isolated from the rhizomes of the plant Curcuma longa Linn.
Curcumin inhibits tumorigenesis during both initiation and promotion
(post-initiation) periods in several experimental animal models. Topical
application of curcumin inhibits benzo[a]pyrene (B[a]P)-mediated formation of
DNA-B[a]P adducts in the epidermis. It also reduces
12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases in skin
inflammation, epidermal DNA synthesis, ornithine decarboxylase (ODC) mRNA level,
ODC activity, hyperplasia, formation of c-Fos, and c-Jun proteins, hydrogen
peroxide, and the oxidized DNA base 5-hydroxymethyl-2'-deoxyuridine (HmdU).
Topical application of curcumin inhibits TPA-induced increases in the percent of
epidermal cells in synthetic (S) phase of the cell cycle. Curcumin is a strong
inhibitor of arachidonic acid-induced edema of mouse ears in vivo and epidermal
cyclooxygenase and lipoxygenase activities in vitro. Commercial curcumin
isolated from the rhizome of the plant Curcuma longa Linn contains 3 major
curcuminoids (approximately 77% curcumin, 17% demethoxycurcumin, and 3%
bisdemethoxycurcumin). Commercial curcumin, pure curcumin, and demethoxycurcumin
are about equipotent as inhibitors of TPA-induced tumor promotion in mouse skin,
whereas bisdemethoxycurcumin is somewhat less active. Topical application of
curcumin inhibits tumor initiation by B[a]P and tumor promotion by TPA in mouse
skin. Dietary curcumin (commercial grade) inhibits B[a]P-induced forestomach
carcinogenesis, N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)-induced duodenal
carcinogenesis, and azoxymethane (AOM)-induced colon carcinogenesis. Dietary
curcumin had little or no effect on
4-(methylnitosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis
and 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast carcinogenesis in mice.
Poor circulating bioavailability of curcumin may account for the lack of lung
and breast carcinogenesis inhibition.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 9591190 [PubMed - indexed for MEDLINE]

282: Free Radic Biol Med. 1997;23(6):838-43.

Free radical reactions of curcumin in membrane models.

Priyadarsini KI.

Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, India.

Free radical reactions of curumin, a lipid soluble antioxidant from turmeric
(Curcuma longa), have been studied with a variety of oxidants using TX 100
micelle as a model membrane. The phenoxyl radicals of curcumin generated by one
electron oxidizing azide radicals in acetonitrile-water mixture and TX 100
micelles show very similar spectral behavior. However, in membrane models the
radical lifetimes and the molar extinction coefficients are significantly
different from the homogeneous solutions. Micellized curcumin reacts with
haloperoxyl radicals, superoxide, and lipid peroxyl radicals with rate constants
of 5 X 10(3), 4.6 X 10(4), and 5.3 X 10(5) M-1s-1, respectively. Curcumin
derived phenoxyl radicals decay by radical-radical reactions in homogeneous
solutions, while in the micelles, radical decay is mostly first order when the
average occupancy of the micelle is less than 1. Implications of these results
in evaluating curcumin as an antioxidant is discussed.

PMID: 9378362 [PubMed - indexed for MEDLINE]

283: Mol Cell Biochem. 1997 Jan;166(1-2):169-75.

Hypolipidemic action of curcumin, the active principle of turmeric (Curcuma
longa) in streptozotocin induced diabetic rats.

Babu PS, Srinivasan K.

Department of Biochemistry and Nutrition, Central Food Technological Research
Institute, Mysore, India.

Streptozotocin-induced diabetic rats were maintained on 0.5% curcumin containing
diet for 8 weeks. Blood cholesterol was lowered significantly by dietary
curcumin in these diabetic animals. Cholesterol decrease was exclusively from
LDL-VLDL fraction. Significant decrease in blood triglyceride and phospholipids
was also brought about by dietary curcumin in diabetic rats. In a parallel
study, wherein diabetic animals were maintained on a high cholesterol diet, the
extents of hypercholesterolemia and phospholipidemia were still higher compared
to those maintained on control diet. Curcumin exhibited lowering of cholesterol
and phospholipid in these animals also. Liver cholesterol, triglyceride and
phospholipid contents were elevated under diabetic conditions. Dietary curcumin
showed a distinct tendency to counter these changes in lipid fractions of liver.
This effect of curcumin was also seen in diabetic animals maintained on high
cholesterol diet. Dietary curcumin also showed significant countering of renal
cholesterol and triglycerides elevated in diabetic rats. In order to understand
the mechanism of hypocholesterolemic action of dietary curcumin, activities of
hepatic cholesterol-7a-hydroxylase and HMG CoA reductase were measured. Hepatic
cholesterol-7a-hydroxylase activity was markedly higher in curcumin fed diabetic
animals suggesting a higher rate of cholesterol catabolism.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 9046034 [PubMed - indexed for MEDLINE]

284: Zhongguo Zhong Yao Za Zhi. 1996 Nov;21(11):651-2, 702.

[Effect of organic fertilizer and mineral fertilizer on the tuber yield of
Curcuma longa L.]

[Article in Chinese]

Li L, Qin S.

Sichuan Institute of Chinese Materia Medica, Chongqing.

Regression method of orthogonal conic substitution with factors was employed to
build up the tuber models for yield, quality and benefit. Three main measures
affecting the tuber yield, quality and benefit were analyzed by these
mathematical models. The effect of agronomic measures on the tuber yield is
human and livestock excreta, rape cake > Ca3(PO4)2 > KCl. The optimal
combination of farming practices has been obtained according to the analysis of
these models.

Publication Types:
English Abstract

PMID: 9812688 [PubMed - indexed for MEDLINE]

285: Mutat Res. 1996 Sep 13;370(2):127-31.

Antimutagenic and anticarcinogenic activity of natural and synthetic
curcuminoids.

Anto RJ, George J, Babu KV, Rajasekharan KN, Kuttan R.

Amala Cancer Research Center, Kerala, India.

Five synthetic curcuminoids and three natural curcuminoids were investigated for
their antimutagenic and anti-promotional activity. The natural curcuminoids,
curcumin I (diferuloylmethane), curcumin II (feruloyl-p-hydroxycinnamoylmethane)
and curcumin III (bis-(p-hydroxycinnamoyl)methane) isolated from Curcuma longa
were found to be potent inhibitors of mutagenesis and crotean oil-induced tumour
promotion. Curcumin III produced 87.6% inhibition to 2-acetamidofluorene (2-AAF)
induced mutagenesis, at a concentration of 100 micrograms/plate, curcumin II and
curcumin I produced 70.5% and 68.3% inhibition at the same concentration. All
the synthetic curcuminoids were found to inhibit 2-AAF-induced mutagenicity
among which salicyl- and anisylcurcuminoids were the most active. Curcumin III
was the most effective anti-promotor among natural curcuminoids. While 90% of
the control animals were having papillomas on the 10th week of tumour
initiation, only 10% of the curcumin III-treated animals, 20% of the curcumin
II-treated animals, and 40% of the curcumin I-treated animals were having
papillomas. Salicylcurcuminoid, which was causing no papillomas by the 10th
week, was the most potent anti-carcinogen among the synthetic curcuminoids.
Piperonal curcuminoid also exhibited anti-promotional activity.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 8879271 [PubMed - indexed for MEDLINE]

286: Zhongguo Zhong Yao Za Zhi. 1996 Sep;21(9):527-9, 574.

[Curcuma longa L. tuber yield simulation model and its application under
combined agronomic measures for good-quality, high-yield and obvious economic
results]

[Article in Chinese]

Li L, Qin S, Song H, Zhang Y, Liao G.

Sichuan Institute of Chinese Materia Medica, Chongqing.

A design of second order orthogonal rotative regression was developed and field
tested, and the tuber models for yield, quality and benefit were simulated and
built. The effect of agronomic measures on the tuber yield is plant density >
phosphorus > sowing date > nitrogen > potassium. There is a clear interrelation
effect among agronomic measures. The results of simulation experiment have shown
that the optimal combination of farming practices can greatly increase the tuber
yield, quality and benefit, and is adjusted according to climate, soil,
ferilizer or manure sources, and so on.

Publication Types:
English Abstract

PMID: 9772639 [PubMed - indexed for MEDLINE]

287: Zhongguo Zhong Yao Za Zhi. 1996 Aug;21(8):462-5, 509.

[Rules of the absorption, distribution and translocation of nitrogen, phosphorus
and potassium in turmeric plant]

[Article in Chinese]

Zhang Y, Li L, Liao G.

Sichuan Institute of Chinese Maleria Medica, Chongqing.

It has been found out that the percentages of nitrogen (N), phosphorus (P) and
potassium (K) in turmeric plant (Curcuma longa) are higher in young organs.
Varying with the growth stages, the nutrient contents of the plant, whose amount
order is K > N > P are the highest in the seedling stage. Nutrient absorption
occurs mainly in the young turmeric forming stage and enriching stage. Nutrient
translocation takes place mainly from leaves and leaf stalks to young and old
turmeric, the rate of P being the highest.

Publication Types:
English Abstract

PMID: 9642404 [PubMed - indexed for MEDLINE]

288: Phytochemistry. 1996 Jun;42(3):599-605.

Inhibition of cyclic AMP-dependent protein kinase by curcumin.

Hasmeda M, Polya GM.

School of Biochemistry, La Trobe University, Bundoora, Victoria, Australia.

Curcumin [diferuloylmethane;
1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione], a major bioactive
secondary metabolite found in the rhizomes of turmeric (Curcuma longa), is an
inhibitor of Ca(2+)- and phospholipid-dependent protein kinase C (PKC) and of
the catalytic subunit (cAK) of cyclic AMP-dependent protein kinase (IC50 values
15 and 4.8 microM, respectively). Curcumin inhibits plant Ca(2+)-dependent
protein kinase (CDPK) (IC50 41 microM), but does not inhibit myosin light chain
kinase or a high affinity 3',5'-cyclic AMP-binding phosphatase. Curcumin
inhibits cAK, PKC and CDPK in a fashion that is competitive with respect to both
ATP and the synthetic peptide substrate employed. The IC50 values for inhibition
of cAK by curcumin are very similar when measured with kemptide (LRRASLG) (in
the presence or absence of ovalbumin) or with casein or histone III-S as
substrates. However, the presence of bovine serum albumin (0.8 mg ml-1) largely
overcomes inhibition of cAK by curcumin.

Publication Types:
Comparative Study

PMID: 8768315 [PubMed - indexed for MEDLINE]

289: Cytobios. 1996;86(346):155-65.

Effect of plant extracts and systemic fungicide on the pineapple fruit-rotting
fungus, Ceratocystis paradoxa.

Damayanti M, Susheela K, Sharma GJ.

Department of Life Sciences, Manipur University, Imphal, India.

Antifungal activities of extracts of sixteen plants were tested against
Ceratocystis paradoxa which causes soft rot of pineapples. Xanthium strumarium
was the most effective followed by Allium sativum. The effectiveness of various
extracts against C. paradoxa was in the decreasing order of Meriandra
bengalensis, Mentha piperita, Curcuma longa, Phlogacanthus thyrsiflorus, Toona
ciliata, Vitex negundo, Azadirachta indica, Eupatorium birmanicum, Ocimum
sanctum and Leucas aspera. Extracts of Cassia tora, Gynura cusimba, Calotropis
gigantea and Ocimum canum showed poor fungitoxicity. Ethanol was suitable for
extraction of the inhibitory substance from X. strumarium. Acetonitrile was
highly toxic to this fungus. Millipore filter-sterilized extracts had a more
inhibitory effect on the fungus than the autoclaved samples. Treatment of
pineapple fruits infested with C. paradoxa by X. strumarium extract reduced the
severity of the disease.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9022263 [PubMed - indexed for MEDLINE]

290: J Ethnopharmacol. 1995 Dec 15;49(3):163-9.

Antifungal activity of turmeric oil extracted from Curcuma longa
(Zingiberaceae).

Apisariyakul A, Vanittanakom N, Buddhasukh D.

Department of Pharmacology, Chiang Mai University, Thailand.

Turmeric oil and curcumin, isolated from Curcuma longa L., were studied against
fifteen isolates of dermatophytes, four isolates of pathogenic molds and six
isolates of yeasts. The inhibitory activity of turmeric oil was tested in
Trichophyton-induced dermatophytosis in guinea pigs. The results showed that all
15 isolates of dermatophytes could be inhibited by turmeric oil at dilutions of
1:40-1:320. None of the isolates of dermatophytes were inhibited by curcumin.
The other four isolates of pathogenic fungi were inhibited by turmeric oil at
dilutions of 1:40-1:80 but none were inhibited by curcumin. All six isolates of
yeasts tested proved to be insensitive to both turmeric oil and curcumin. In the
experimental animals, turmeric oil (dilution 1:80) was applied by dermal
application on the 7th day following dermatophytosis induction with Trichophyton
rubrum. An improvement in lesions was observed in 2-5 days and the lesions
disappeared 6-7 days after the application of turmeric oil.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 8824742 [PubMed - indexed for MEDLINE]

291: Cancer Lett. 1995 Sep 4;96(1):87-93.

Postnatal modulation of hepatic biotransformation system enzymes via
translactational exposure of F1 mouse pups to turmeric and curcumin.

Singh A, Singh SP, Bamezai R.

Human Genetics Laboratory, School of Life Sciences, Jawahalal Nehru University,
New Delhi, India.

The potential for the transfer of active principle(s) of turmeric (Curcuma longa
L.) and curcumin (major pigment in turmeric) via translactational route and its
modulatory influence on the hepatic biotransformation system enzymes in the
lactating dams and their suckling offspring was assessed. Turmeric (4 g/kg b.w.
per day) and curcumin (0.4 g/kg b.w. per day) induced significant (P < 0.01)
increase in the hepatic levels of glutathione S-transferase (GST) and acid
soluble sulfhydryl (-SH) after 14 or 21 days treatment in lactating dams and
translactationally exposed F1 pups. However the lower dose of curcumin (0.2 g/kg
b.w. per day) could modulate hepatic GST activity (P < 0.05) and -SH (P < 0.01)
only after 21 days of treatment in dams and pups. Cytochrome b5 and cytochrome
P450 levels were significantly elevated (P < 0.05) in the dams as well as their
suckling pups of both 14 and 21 days age groups at the selected dose levels of
turmeric (4 g/kg b.w.) and curcumin (0.4 g/kg b.w.). The induction in hepatic
biotransformation system enzymes in lactating dams and F1 progeny suggests the
passage of active constituents and/or metabolites of turmeric and curcumin via
the translactational route.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 7553612 [PubMed - indexed for MEDLINE]

292: Biosci Biotechnol Biochem. 1995 Sep;59(9):1609-12.

Antioxidative activity of tetrahydrocurcuminoids.

Osawa T, Sugiyama Y, Inayoshi M, Kawakishi S.

Department of Applied Biological Sciences, Nagoya University, Japan.

In order to develop a new type of antioxidative compound which has both the
phenolic and beta-diketone moiety in the same molecule, we converted three known
curcuminoids, curcumin (diferuloylmethane, U1),
(4-hydroxy-3-methoxycinnamoyl)methane (U2), and bis-(4-hydroxycinnamoyl)methane
(U3), which are the natural antioxidants of Curcuma longa L. (tumeric), to
tetrahydrocurcuminoids (THU1, THU2, and THU3, respectively) by hydrogenation,
and evaluated their antioxidative activity by using linoleic acid as the
substrate in an ethanol/water system. Further, we used the rabbit erythrocyte
membrane ghost and rat liver microsome as in vitro systems and determined the
antioxidative activity of these curcuminoids. When we evaluated their
antioxidative activity by these assays, it was found that THU1 had the strongest
antioxidative activity among all curcuminoids in each assay system. THU1 has
been reported to be one of the main metabolites of U1 in vivo [Holder et al.,
Xenobiotica, 8, 761-768 (1978)]. These results suggest that THU1 must play an
important role in the antioxidative mechanism of U1 in vivo by converting U1
into THU1.

PMID: 8520105 [PubMed - indexed for MEDLINE]

293: Cancer Lett. 1995 Jul 20;94(1):79-83.

Anti-tumour and antioxidant activity of natural curcuminoids.

Ruby AJ, Kuttan G, Babu KD, Rajasekharan KN, Kuttan R.

Amala Cancer Research Centre, Kerala, India.

Matural curcuminoids, curcumin, I, II and III isolated from turmeric (Curcuma
longa) were compared for their cytotoxic, tumour reducing and antioxidant
activities. Curcumin III was found to be more active than the other two as a
cytotoxic agent and in the inhibition of Ehrlich ascites tumour in mice (ILS
74.1%). These compounds were also checked for their antioxidant activity which
possibly indicates their potential use as anti-promoters. The amount of
curcuminoids (I, II and III) needed for 50% inhibition of lipid peroxidation was
20, 14 and 11 g/m. Concentrations needed for 50% inhibition of superoxides were
6.25, 4.25 and 1.9 micrograms/ml and those for hydroxyl radical were 2.3, 1.8
and 1.8 micrograms/ml, respectively. The ability of these compounds to suppress
the superoxide production by macrophages activated with
phorbol-12-myristate-13-acetate (PMA) indicated that all the three curcuminoids
inhibited superoxide production and curcumin III produced maximum effect. These
results indicate that curcumin III is the most active of the curcuminoids
present in turmeric. Synthetic curcumin I and III had similar activity to
natural curcumins.

PMID: 7621448 [PubMed - indexed for MEDLINE]

294: J Ethnopharmacol. 1995 Jul 7;47(2):59-67.

The anti-oxidant activity of turmeric (Curcuma longa).

Selvam R, Subramanian L, Gayathri R, Angayarkanni N.

Department of Medical Biochemistry, Dr. A.L. Mudaliar Post Graduate Institute of
Basic Medical Sciences, University of Madras, Taramani, India.

The turmeric anti-oxidant protein (TAP) had been isolated from the aqueous
extract of turmeric. The anti-oxidant principle was found to be a heat stable
protein. Trypsin treatment abolished the anti-oxidant activity. The anti-oxidant
principle had an absorbance maximum at 280 nm. After gel filtration, the protein
showed a 2-fold increase in anti-oxidant activity and showed 2 bands in the
SDS-PAGE with approximate molecular weight range of 24,000 Da. The protein
showed a concentration-dependent inhibitory effect on the promoter induced lipid
peroxidation. A 50% inhibitory activity of lipid peroxidation was observed at a
protein concentration of 50 micrograms/ml. Ca(2+)-ATPase of rat brain homogenate
was protected to nearly 50% of the initial activity from the lipid peroxidant
induced inactivation by this protein. This protection of Ca(2+)-ATPase activity
was found to be associated with the prevention of loss of -SH groups.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 7500637 [PubMed - indexed for MEDLINE]

295: Biochem Pharmacol. 1995 May 26;49(11):1551-6.

Inhibition of tumor necrosis factor by curcumin, a phytochemical.

Chan MM.

Department of Biological Sciences, Rutgers, State University of New Jersey,
Piscataway 08855-1059, USA.

Curcumin, contained in the rhizome of the plant Curcuma longa Linn, is a
naturally occurring phytochemical that has been used widely in India and
Indonesia for the treatment of inflammation. The pleiotropic cytokine tumor
necrosis factor-alpha (TNF) induces the production of interleukin-1 beta (IL-1),
and, together, they play significant roles in many acute and chronic
inflammatory diseases. They have been implicated in the pathogenesis of
intracellular parasitic infections, atherosclerosis, AIDS and autoimmune
disorders. This report shows that, in vitro, curcumin, at 5 microM, inhibited
lipopolysaccharide (LPS)-induced production of TNF and IL-1 by a human monocytic
macrophage cell line, Mono Mac 6. In addition, it demonstrates that curcumin, at
the corresponding concentration, inhibited LPS-induced activation of nuclear
factor kappa B and reduced the biological activity of TNF in L929 fibroblast
lytic assay.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 7786295 [PubMed - indexed for MEDLINE]

296: Biochem Pharmacol. 1995 Apr 18;49(8):1165-70.

Inhibition of human immunodeficiency virus type-1 integrase by curcumin.

Mazumder A, Raghavan K, Weinstein J, Kohn KW, Pommier Y.

Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD
20892-4255, USA.

Curcumin (diferuloylmethane) is the yellow pigment in turmeric (Curcuma longa
L.) that is widely used as a spice, food coloring (curry) and preservative.
Curcumin exhibits a variety of pharmacological effects including antitumor,
anti-inflammatory, and anti-infectious activities and is currently in clinical
trials for AIDS patients. The effects of curcumin have been determined on
purified human immunodeficiency virus type 1 (HIV-1) integrase. Curcumin has an
inhibitory concentration50 (IC50) for strand transfer of 40 microM. Inhibition
of an integrase deletion mutant containing only amino acids 50-212 suggests that
curcumin interacts with the integrase catalytic core. Two structural analogs,
methyl cinnamate and chlorogenic acid, were inactive. Energy minimization
studies suggest that the anti-integrase activity of curcumin could be due to an
intramolecular stacking of two phenyl rings that brings the hydroxyl groups into
close proximity. The present data suggest that HIV-1 integrase inhibition may
contribute to the antiviral activity of curcumin. These observations suggest new
strategies for antiviral drug development that could be based upon curcumin as a
lead compound for the development of inhibitors of HIV-1 integrase.

Publication Types:
Research Support, U.S. Gov't, P.H.S.

PMID: 7748198 [PubMed - indexed for MEDLINE]

297: Prostaglandins Leukot Essent Fatty Acids. 1995 Apr;52(4):223-7.

Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits
aggregation and alters eicosanoid metabolism in human blood platelets.

Srivastava KC, Bordia A, Verma SK.

Department of Environmental Medicine, Odense University, Denmark.

In traditional medicine, Ayurveda, several spices and herbs are held to possess
medicinal properties. Earlier we have reported that extracts from several
spices, including turmeric, inhibit platelet aggregation and modulate eicosanoid
biosynthesis. Due to their eicosanoid-modulating property, it was suggested that
the spices may serve to provide clues to drugs directed to arachidonic acid (AA)
pathway enzymes as pharmacological targets. Curcumin, a major component of
turmeric, inhibited platelet aggregation induced by arachidonate, adrenaline and
collagen. This compound inhibited thromboxane B2 (TXB2) production from
exogenous [14C] arachidonate in washed platelets with a concomitant increase in
the formation of 12-lipoxygenase products. Moreover, curcumin inhibited the
incorporation of [14C]AA into platelet phospholipids and inhibited the
deacylation of AA-labelled phospholipids (liberation of free AA) on stimulation
with calcium ionophore A23187. Curcumin's anti-inflammatory property may, in
part, be explained by its effects on eicosanoid biosynthesis.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 7784468 [PubMed - indexed for MEDLINE]

298: J Ethnopharmacol. 1994 Dec;44(3):211-7.

Adjuvant chemoprevention of experimental cancer: catechin and dietary turmeric
in forestomach and oral cancer models.

Azuine MA, Bhide SV.

Division of Pharmaceutical Microbiology and Biotechnology, National Institute
for Pharmaceutical Research and Development, Abuja, Nigeria.

Catechin and dietary turmeric (Curcuma longa) were used as chemopreventive
agents in benzo[a]pyrene induced forestomach tumors in Swiss mice and
methyl-(acetoxymethyl)-nitrosamine induced oral mucosal tumors in Syrian golden
hamsters. Catechin in drinking water and dietary turmeric significantly
inhibited the tumor burden and tumor incidence in both tumor models. The
induction of oral tumors in golden hamsters was delayed by catechin and dietary
turmeric. Adjuvant chemoprevention utilising both catechin and dietary turmeric
inhibited both the gross tumor yield and burden more effectively than when
compared to individual components in both tumor models. A single i.p. injection
of catechin to male Swiss mice induced increased forestomach and hepatic
glutathione S-transferase (GST) activity when compared to controls. These
findings suggest that catechin and turmeric which are regularly consumed natural
products, are effective in mice or golden hamsters as chemopreventive agents.

Publication Types:
Comparative Study

PMID: 7898128 [PubMed - indexed for MEDLINE]

299: Cancer Res. 1994 Nov 15;54(22):5841-7.

Inhibitory effects of dietary curcumin on forestomach, duodenal, and colon
carcinogenesis in mice.

Huang MT, Lou YR, Ma W, Newmark HL, Reuhl KR, Conney AH.

Department of Chemical Biology and Pharmacognosy, College of Pharmacy, Rutgers,
State University of New Jersey, Piscataway 08855-0789.

Curcumin (diferuloylmethane), a yellow pigment that is obtained from the
rhizomes of Curcuma longa Linn., is a major component of turmeric and is
commonly used as a spice and food-coloring agent. The inhibitory effects of
feeding commercial grade curcumin (77% curcumin, 17% demethoxycurcumin, and 3%
bisdemethoxycurcumin) in AIN 76A diet on carcinogen-induced tumorigenesis in the
forestomach, duodenum, and colon of mice were evaluated. Administration p.o. of
commercial grade curcumin in the diet inhibited benzo(a)pyrene-induced
forestomach tumorigenesis in A/J mice,
N-ethyl-N'-nitro-N-nitrosoguanidine-induced duodenal tumorigenesis in C57BL/6
mice, and azoxymethane (AOM)-induced colon tumorigenesis in CF-1 mice. Dietary
commercial grade curcumin was given to mice at: (a) 2 weeks before, during, and
for 1 week after carcinogen administration (during the initiation period); (b) 1
week after carcinogen treatment until the end of the experiment (during the
postinitiation period); or (c) during both the initiation and postinitiation
periods. Feeding 0.5-2.0% commercial grade curcumin in the diet decreased the
number of benzo(a)pyrene-induced forestomach tumors per mouse by 51-53% when
administered during the initiation period and 47-67% when administered during
the postinitiation period. Feeding 0.5-2.0% commercial grade curcumin in the
diet decreased the number of N-ethyl-N'-nitro-N-nitrosoguanidine-induced
duodenal tumors per mouse by 47-77% when administered during the postinitiation
period. Administration of 0.5-4.0% commercial grade curcumin in the diet both
during the initiation and postinitation periods decreased the number of
AOM-induced colon tumors per mouse by 51-62%. Administration of 2% commercial
grade curcumin in the diet inhibited the number of AOM-induced colon tumors per
mouse by 66% when fed during the initiation period and 25% when fed during the
postinitiation period. The ability of commercial grade curcumin to inhibit
AOM-induced colon tumorigenesis is comparable to that of pure curcumin (purity
greater than 98%). Administration of pure or commercial grade curcumin in the
diet to AOM-treated mice resulted in development of colon tumors which were
generally smaller in number and size as compared to the control group of
AOM-treated mice. These results indicate that not only did curcumin inhibit the
number of tumors per mouse and the percentage of mice with tumors but it also
reduced tumor size. Histopathological examination of the tumors showed that
dietary curcumin inhibited the number of papillomas and squamous cell carcinomas
of the forestomach as well as the number of adenomas and adenocarcinomas of the
duodenum and colon.

Publication Types:
Research Support, U.S. Gov't, P.H.S.

PMID: 7954412 [PubMed - indexed for MEDLINE]

300: Plant Foods Hum Nutr. 1994 Oct;46(3):187-93.

Influence of spices on protein utilisation of winged bean (Psophocarpus
tetragonolobus) and horsegram (Dolichos biflorus).

Pradeep KU, Geervani P.

Postgraduate & Research Centre, Faculty of Home Science, A.P. Agricultural
University, Hyderabad, India.

The influence of a mixture of eleven spices commonly consumed in India on the
utilisation of protein from boiled winged bean (Psophocarpus tetragonolobus) and
horsegram (Dolichos biflorus) was studied at 10 and 20 percent level of protein
intake in experimental rats. Spices used in the mixture include red chillies
(Capsicum annum), black pepper (Piper nigrum), coriander (Coriandrum sativum),
cumin (Cuminum cyminum), garlic (Allium sativum), ajowan (Carum copticum),
turmeric (Curcuma longa), caraway seeds (Carum carui) and fennel seeds
(Foeniculum vulgare). Addition of this spice mixture at 1.5% level of the diet
decreased the TD of both legumes, significantly only in the case of horsegram. A
significant increase was observed in the BV of both the legumes at both levels
of protein tested.

PMID: 7855088 [PubMed - indexed for MEDLINE]

301: Int J Pancreatol. 1994 Jun;15(3):187-93.

Effect of intraduodenal infusion of tocamphyl on pancreatic exocrine secretion
and gastrointestinal hormone release in rats.

Imamura M, Yamauchi H, Chey WY.

Department of Surgery, National Sendai Hospital, Japan.

Tocamphyl is a synthetic choleretic that is derived from a root extract of
Curcuma longa, L. We investigated the effect of tocamphyl on pancreatic exocrine
secretion and bile flow, and on the release of some gastrointestinal hormones,
by administering it intraduodenally using anesthetized rats. Tocamphyl
stimulated pancreatic exocrine secretion in terms of volume and amylase output
in a dose-related manner. Neither a CCK-receptor antagonist, CR1505
(loxiglumide), nor atropine sulfate infused intravenously suppressed the
stimulatory effects of tocamphyl on pancreatic exocrine secretion and bile flow.
The stimulatory effect on bile flow was stronger than that on pancreatic
exocrine secretion. Plasma secretin levels were augmented with the increasing
doses of tocamphyl, but CCK levels were not. These results indicate that
intraduodenally administered tocamphyl stimulates pancreatic exocrine secretion
and bile flow, and suggest that the stimulatory action is, at least in part,
mediated by secretin, but not by either CCK or the cholinergic pathway.

PMID: 7930779 [PubMed - indexed for MEDLINE]

302: Food Chem Toxicol. 1994 Mar;32(3):279-83.

Effect of dietary turmeric (Curcuma longa) on iron-induced lipid peroxidation in
the rat liver.

Reddy AC, Lokesh BR.

Department of Biochemistry and Nutrition, Central Food Technological Research
Institute, Mysore, India.

Male Wistar rats were fed a control diet or the control diet supplemented with
1% (by weight) turmeric for 10 wk. In rats injected with 30 mg Fe2+/kg body
weight, lipid peroxidation was 29 and 35% lower in liver homogenates and
microsomes, respectively, of turmeric-fed rats than in those of rats fed the
control diet. The activities of superoxide dismutase, catalase and glutathione
peroxidase were higher (by 19, 19 and 20%, respectively) in liver homogenates of
rats fed the turmeric-containing diet in comparison with the controls. These
studies indicate that dietary turmeric lowers lipid peroxidation by enhancing
the activities of antioxidant enzymes.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 8157223 [PubMed - indexed for MEDLINE]

303: Photochem Photobiol. 1994 Mar;59(3):295-302.

Spectral and photochemical properties of curcumin.

Chignell CF, Bilski P, Reszka KJ, Motten AG, Sik RH, Dahl TA.

Laboratory of Molecular Biophysics, National Institute of Environmental Health
Sciences, Research Triangle Park, NC 27709.

Curcumin, bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, is a natural
yellow-orange dye derived from the rhizome of Curcuma longa, an East Indian
plant. In order to understand the photobiology of curcumin better we have
studied the spectral and photochemical properties of both curcumin and
4-(4-hydroxy-3-methoxy-phenyl)-3-buten-2-one (hC, half curcumin) in different
solvents. In toluene, the absorption spectrum of curcumin contains some
structure, which disappears in more polar solvents, e.g. ethanol, acetonitrile.
Curcumin fluorescence is a broad band in acetonitrile (lambda max = 524 nm),
ethanol (lambda max = 549 nm) or micellar solution (lambda max = 557 nm) but has
some structure in toluene (lambda max = 460, 488 nm). The fluorescence quantum
yield of curcumin is low in sodium dodecyl sulfate (SDS) solution (phi = 0.011)
but higher in acetonitrile (phi = 0.104). Curcumin produced singlet oxygen upon
irradiation (lambda > 400 nm) in toluene or acetonitrile (phi = 0.11 for 50
microM curcumin); in acetonitrile curcumin also quenched 1O2 (kq = 7 x 10(6) M-1
s-1). Singlet oxygen production was about 10 times lower in alcohols and was
hardly detectable when curcumin was solubilized in a D2O micellar solution of
Triton X-100. In SDS micelles containing curcumin no singlet oxygen
phosphorescence could be observed. Curcumin photogenerates superoxide in toluene
and ethanol, which was detected using the electron paramagnetic
resonance/spin-trapping technique with 5,5-dimethyl-pyrroline-N-oxide as a
trapping agent. Unidentified carbon-centered radicals were also
detected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 8016208 [PubMed - indexed for MEDLINE]

304: Photochem Photobiol. 1994 Mar;59(3):290-4.

Photocytotoxicity of curcumin.

Dahl TA, Bilski P, Reszka KJ, Chignell CF.

Department of Pharmacology & Experimental Therapeutics, School of Veterinary
Medicine, Tufts University, Boston, MA 02111.

Curcumin, bis(4-hydroxy-3-methoxyphenyl)-1,6-diene-3,5-dione, is a yellow-orange
dye derived from the rhizome of the plant Curcuma longa. Curcumin has
demonstrated phototoxicity to several species of bacteria under aerobic
conditions (Dahl, T. A., et al., 1989, Arch. Microbiol. 151 183), denoting
photodynamic inactivation. We have now found that curcumin is also phototoxic to
mammalian cells, using a rat basophilic leukemia cell model, and that this
phototoxicity again requires the presence of oxygen. The spectral and
photochemical properties of curcumin vary with environment, resulting in the
potential for multiple or alternate pathways for the exertion of photodynamic
effects. For example, curcumin photogenerates singlet oxygen and reduced forms
of molecular oxygen under several conditions relevant to cellular environments.
In addition, we detected carbon-centered radicals, which may lead to oxidation
products (see accompanying paper). Such products may be important reactants in
curcumin's phototoxicity since singlet oxygen and reduced oxygen species alone
could not explain the biological results, such as the relatively long lifetime
(t1/2 = 27 s) of the toxicant responsible for decreased cell viability.

PMID: 8016207 [PubMed - indexed for MEDLINE]

305: Stem Cells. 1994 Jan;12(1):53-63.

Highlight on the studies of anticancer drugs derived from plants in China.

Han R.

Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union
Medical College, Beijing.

Recent progress on the study of anticancer drugs originating from plants in
China is reviewed in this paper. Guided by the experience of traditional Chinese
medicine, several new drugs have been found. Indirubin from Indigofera tinctoria
is useful for the treatment of chronic myelocytic leukemia. Irisquinone from
Iris latea pallasii and 10-hydroxy camptothecin from Camptotheca accuminata have
exhibited definite activity on rodent tumors. Recent studies indicate that
ginsenoside Rh2 is an inducer of cell differentiation in melanoma B-16 cells in
vitro. Pharmacological studies have demonstrated that curcumin from Curcuma
longa is an antimutagen as well as an antipromotor for cancer. Daidzein and
acetyl boswellic acid have been shown to be effective inducers of cell
differentiation in HL-60 cells. Guided by the chemotaxonomic principle of
plants, harringtonine and homoharringtonine isolated from Cephalotaxus
hainanesis have exhibited significant antileukemia activity and are widely used
in clinics in China. Taxol from Taxus chinensis has been shown to be an
important new anticancer drug with unique chemical structure and mechanism of
action. The continuous search for new anticancer drugs from plants will be a
fruitful frontier in cancer treatment and chemoprevention.

Publication Types:
In Vitro

PMID: 8142920 [PubMed - indexed for MEDLINE]

306: Bioorg Med Chem. 1993 Dec;1(6):415-22.

Inhibition of the HIV-1 and HIV-2 proteases by curcumin and curcumin boron
complexes.

Sui Z, Salto R, Li J, Craik C, Ortiz de Montellano PR.

Department of Pharmaceutical Chemistry, School of Pharmacy, University of
California, San Francisco 94143-0446.

Curcumin, a relatively non-toxic natural product isolated from Curcuma longa, is
a modest inhibitor of the HIV-1 (IC50 = 100 microM) and HIV-2 (IC50 = 250
microM) proteases. Simple modifications of the curcumin structure raise the IC50
value but complexes of the central dihydroxy groups of curcumin with boron lower
the IC50 to a value as low as 6 microM. The boron complexes are also
time-dependent inactivators of the HIV proteases. The increased affinity of the
boron complexes may reflect binding of the orthogonal domains of the inhibitor
in interesecting sites within the substrate-binding cavity of the enzyme, while
activation of the alpha, beta-unsaturated carbonyl group of curcumin by
chelation to boron probably accounts for time-dependent inhibition of the
enzyme.

Publication Types:
Research Support, U.S. Gov't, P.H.S.

PMID: 8087563 [PubMed - indexed for MEDLINE]

307: J Med Assoc Thai. 1993 Nov;76(11):601-5.

Curcuma longa Linn. in the treatment of gastric ulcer comparison to liquid
antacid: a controlled clinical trial.

Kositchaiwat C, Kositchaiwat S, Havanondha J.

Medical Section, Ratchaburi Hospital, Ministry of Public Health, Thailand.

Publication Types:
Clinical Trial
Comparative Study
Controlled Clinical Trial
Research Support, Non-U.S. Gov't

PMID: 7964234 [PubMed - indexed for MEDLINE]

308: Chem Pharm Bull (Tokyo). 1993 Sep;41(9):1640-3.

Nematocidal activity of turmeric: synergistic action of curcuminoids.

Kiuchi F, Goto Y, Sugimoto N, Akao N, Kondo K, Tsuda Y.

Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.

A new curcuminoid, cyclocurcumin (IV), was isolated from the nematocidally
active fraction of turmeric, the rhizome of Curcuma longa, together with three
known curcuminoids, curcumin (I), demethoxycurcumin (II) and
bisdemethoxycurcumin (III). The structure of IV was elucidated on the basis of
spectral data and confirmed by the partial synthesis from curcumin (I). Although
the above curcuminoids were ineffective when they were applied independently,
the nematocidal activity increased remarkably when they were mixed, suggesting a
synergistic action between them.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 8221978 [PubMed - indexed for MEDLINE]

309: Natl Toxicol Program Tech Rep Ser. 1993 Aug;427:1-275.

NTP Toxicology and Carcinogenesis Studies of Turmeric Oleoresin (CAS No.
8024-37-1) (Major Component 79%-85% Curcumin, CAS No. 458-37-7) in F344/N Rats
and B6C3F1 Mice (Feed Studies).

National Toxicology Program .

Turmeric oleoresin is the organic extract of turmeric, a ground powder from the
root of the Curcuma plant, and is added to food items as a spice and coloring
agent. Turmeric oleoresin, turmeric, and curcumin (the major component found in
turmeric) were nominated by the National Cancer Institute and the Food and Drug
Administration for study because these chemicals are used in food items and
curry powders, and there was little information on their toxic or carcinogenic
properties. Pure curcumin was not available in sufficient quantities for study,
and a turmeric oleoresin with a high curcumin content (79% to 85%) was selected
for evaluation. Toxicity and carcinogenicity studies were conducted by
administering turmeric oleoresin in feed to groups of male and female F344/N
rats and B6C3F1 mice for 13 weeks and 2 years. Genetic toxicology studies were
conducted in Salmonella typhimurium and cultured Chinese hamster ovary cells.
13-WEEK STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were fed
diets containing 0, 1,000, 5,000, 10,000, 25,000, or 50,000 ppm turmeric
oleoresin. All rats survived until the end of the study. The final mean body
weight of males receiving 50,000 ppm was 5% lower than that of the controls.
Feed consumption by exposed male and female rats was similar to that by the
controls. Dietary levels of 1,000, 5,000,10,000, 25,000, or 50,000 ppm turmeric
oleoresin were estimated to deliver average daily doses of 50, 250, 480, 1,300,
or 2,600 mg/kg body weight to males and 60, 300, 550, 1,450, or 2,800 mg/kg to
females. The absolute and relative liver weights of female rats and the relative
liver weights of male rats receiving 5,000, 10,000, 25,000, and 50,000 ppm were
significantly greater than those of the controls. There were no biologically
significant differences in hematologic, clinical chemistry, or urinalysis
parameters. Clinical findings included stained fur, and discolored feces and
urine of exposed animals, presumably due to the parent compound or its
metabolites. Hyperplasia of the mucosal epithelium was observed in the cecum and
colon of male and female rats that received 50,000 ppm. 13-WEEK STUDY IN MICE:
Groups of 10 male and 10 female B6C3F1 mice were fed diets containing 0,1,000,
5,000,10,000, 25,000, or 50,000 ppm turmeric oleoresin. There were no deaths
attributed to turmeric oleoresin and the final mean body weight gains and final
mean body weights of all exposed groups of male and female mice were similar to
those of the controls. Feed consumption by exposed male and female mice was
similar to that by the controls. Dietary levels of 1,000, 5,000,10,000, 25,000,
or 50,000 ppm turmeric oleoresin were estimated to deliver average daily doses
of 150, 750, 1,700, 3,850, or 7,700 mg/kg body weight to males and 200, 1,000,
1,800, 4,700 or 9,300 mg/kg to females. Absolute and relative liver weights of
male mice that received 5,000 ppm and male and female mice that received 10,000,
25,000 and 50,000 ppm were significantly greater than those of the controls.
Clinical findings in mice included stained fur, and discolored feces and urine.
There were no biologically significant differences in hematologic, clinical
chemistry, or urinalysis parameters, and there were no chemical related
histopathologic lesions. 2-YEAR STUDY IN RATS: The exposure level selection for
the 2-year study was based on the 13-week study, which showed that rats could
tolerate diets containing up to 50,000 ppm. Groups of 60 male and 60 female
F344/N rats were fed diets containing 2,000, 10,000, or 50,000 ppm turmeric
oleoresin for 104 (males) or 103 (females) weeks, which were estimated to
deliver average daily doses of 80, 460, or 2,000 mg/kg to males and 90, 440, or
2,400 mg/kg to females. Nine or 10 rats from each exposure group were evaluated
after 15 months. Survival, Mean Body Weights, Feed Consumption, and Clinical
Findings: Survival of exposed male and female rats was similar to that of the
controls (male: O ppm, 18/50; 2,000 ppm, 17/50; 10,000 ppm, 15/50; 50,000 ppm,
17/50; female: 33/50, 27/50, 28/50, 34/50). Th50, 28/50, 34/50). The final mean
body weights of all exposed male rats and female rats receiving 2,000 and 10,000
ppm were similar to those of the controls. The final mean body weights of male
and female rats that received 50,000 ppm were slightly lower (up to 10&percnt;)
than those of the controls throughout much of the study. Feed consumption by
exposed male and female rats was similar to that by controls throughout the
study. The absolute and relative liver weights of female rats receiving 10,000
or 50,000 ppm were significantly greater than those of controls at the 15-month
interim evaluation. There were no clinical findings related to toxicity.
Hematology and Clinical Chemistry: In male and female rats receiving 50,000 ppm
the hematocrit values, hemoglobin concentrations, and erythrocyte counts at the
15-month interim evaluation were significantly lower than those in the controls.
In addition, platelet counts in male and female rats that received 50,000 ppm
and reticulocyte counts in male rats that received 50,000 ppm were significantly
higher than those in the controls. No biologically significant differences were
observed in clinical chemistry parameters. Pathology Findings: Chemical-related
nonneoplastic lesions occurred in the gastrointestinal tract of rats that
received 50,000 ppm. Males receiving 50,000 ppm had increased incidences of
ulcers, hyperplasia, and hyperkeratosis of the forestomach. Male and female rats
that received 50,000 ppm had ulcers, chronic active inflammation, and
hyperplasia of the cecum. Similar lesions also occurred in the colon of males
receiving 50,000 ppm. Male and female rats that received 50,000 ppm and male
rats that received 10,000 ppm had significantly increased incidences of sinus
ectasia of the mesenteric Iymph node. The incidences of clitoral gland adenoma
in all exposed groups of female rats were significantly increased. Clitoral
gland carcinomas occurred in one control female and in four 2,000 ppm females,
but not in females that received 10,000 or 50,000 ppm. The incidences of
clitoral gland adenoma or carcinoma (combined) in all exposed groups of female
rats were similar (6/50, 16/48, 15/47, 16/49) and did not increase with exposure
level. The incidence of clitoral gland hyperplasia was similar among exposed and
control groups of female rats (7/50, 5/48, 4/47, 7149). 2-YEAR STUDY IN MICE:
The exposure level selection for the 2-year study was based on the 13-week
study, which showed that mice could tolerate diets containing up to 50,000 ppm.
Groups of 60 male and 60 female B6C3F1 mice were fed diets containing 2,000,
10,000, or 50,000 ppm turmeric oleoresin for 103 weeks, which were estimated to
deliver average daily doses of 220, 520, or 6,000 mg/kg to males and 320,1,620,
or 8,400 mg/kg to females. Nine or 10 mice from each exposure group were
evaluated after 15 months. Survival, Mean Body Weights, Feed Consumption, and
Clinical Findings: Survival of exposed male and female mice was similar to that
of the controls (male: O ppm, 43/50; 2,000 ppm, 43/50; 10,000 ppm, 37/50; 50,000
ppm 42/50; female: 39/50, 41/50, 34/50, 42/50). The mean body weight of female
mice receiving 50,000 ppm was slightly lower (up to 12&percnt;) than that of the
controls from about week 25. The final mean body weights of males that received
50,000 ppm and females that received 10,000 and 50,000 ppm were significantly
lower than those of controls. The final mean body weights of other exposed
groups of male and female mice were similar to those of the controls. Feed
consumption by exposed male and female mice was similar to that by the controls
throughout the study. The absolute and relative liver weights of male and female
mice receiving 10,000 and 50,000 ppm were significantly greater than those of
the controls at the l5-month interim evaluation. There were no clinical findings
related to toxicity. Hematology and Clinical Chemistry: No biologically
significant differences were observed in hematologic parameters. The alkaline
phosphatase values of male and female mice that received 10,000 and 50,000 ppm
were significantly higher than those of controls at the 15-month interim
evaluation. Pathology Findings: The incidences of hepatocellular adenoma in male
and female mice receiving 10,000 ppm, but not those in mice receiving 2,000 or
50,000 ppm, were significantly increased (male: 25/50, 28/50, 35/50, 30/50;
female: 7/50, 8/50, 19/51, 14/50). The number of male and female mice in the
10,000 and 50,000 ppm groups with multiple hepatocellular neoplasms was
significantly greater than that in the controls. The incidences of
hepatocellular carcinoma were similar among exposed and control groups. In
contrast to rats, there were no chemical-related nonneoplastic lesions of the
gastrointestinal tract in mice. Three males that received 2,000 ppm and three
males that received 10,000 ppm had carcinomas of the small intestine; neoplasms
of the small intestine were not observed in control males or in males that
received 50,000 ppm. Female mice receiving 50,000 ppm had a significantly
increased incidence of thyroid gland follicular cell hyperplasia. GENETIC
TOXICOLOGY: Turmeric oleoresin was not mutagenic in Salmonella typhimurium
strains TA100, TA1535, TA1537, or TA98 with or without exogenous metabolic
activation (S9). It induced small but significant increases in sister chromatid
exchanges and chromosomal aberrations in cultured Chinese hamster ovary cells.
The positive response in the sister chromatid exchange test occurred in the
presence of S9, whereas the aberrations response occurred without S9.
CONCLUSIONS: Under the conditions of these 2-year feed studies, there was no
evidence of carcinogenic activity of turmeric oleoresin in male F344/N rats
administered 2,000, 10,000, or 50,000 ppm. There was equivocal evidence of
carcinogenic activity of turmeric oleoresin in female F344/N rats based on
increased incidences of clitoral gland adenomas in the exposed groups. There was
equivocal evidence of carcinogenic activity of turmeric oleoresin in male B6C3F1
mice based on a marginally increased incidence of hepatocellular adenoma at the
10,000 ppm level, and the occurrence of carcinomas of the small intestine in the
2,000 and 10,000 ppm groups. There was equivocal evidence of carcinogenic
activity of turmeric oleoresin in female B6C3F1 mice based on an increased
incidence of hepatocellular adenomas in the 10,000 ppm group. Turmeric oleoresin
ingestion was also associated with increased incidences of ulcers, hyperplasia,
and inflammation of the forestomach, cecum, and colon in male rats and of the
cecum in female rats. In female mice, ingestion of diets containing turmeric
oleoresin was also associated with an increased incidence of thyroid gland
follicular cell hyperplasia. Synonyms for Turmeric Oleoresin: curcuma oil; oil
of turmeric; turmeric oil; curcuma longa oils; curcuma long oil; Curcumin
Synonyms for Curcumin:
1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione; C.I. Natural Yellow
3; C.I. 75300; Curcuma; diferuloylmethane; E 100; Haidr; Halad; Haldar; Halud;
HSDB 4334; Indian Saffron; kacha haldi; Kurkumin; merita earth; Souchet;
Turmeric Yellow; yellow ginger; yellow root; Yo-kin; Zlut Prirodni 3;
NCI-C613253

PMID: 12616304 [PubMed - as supplied by publisher]

310: J Ethnopharmacol. 1993 Mar;38(2-3):113-9.

Mechanism of antiinflammatory actions of curcumine and boswellic acids.

Ammon HP, Safayhi H, Mack T, Sabieraj J.

Department of Pharmacology, Eberhard-Karls University, Tubingen, FRG.

Curcumine from Curcuma longa and the gum resin of Boswellia serrata, which were
demonstrated to act as anti-inflammatories in in vivo animal models, were
studied in a set of in vitro experiments in order to elucidate the mechanism of
their beneficial effects. Curcumine inhibited the 5-lipoxygenase activity in rat
peritoneal neutrophils as well as the 12-lipoxygenase and the cyclooxygenase
activities in human platelets. In a cell free peroxidation system curcumine
exerted strong antioxidative activity. Thus, its effects on the dioxygenases are
probably due to its reducing capacity. Boswellic acids were isolated from the
gum resin of Boswellia serrata and identified as the active principles.
Boswellic acids inhibited the leukotriene synthesis via 5-lipoxygenase, but did
not affect the 12-lipoxygenase and the cyclooxygenase activities. Additionally,
boswellic acids did not impair the peroxidation of arachidonic acid by iron and
ascorbate. The data suggest that boswellic acids are specific, non-redox
inhibitors of leukotriene synthesis either interacting directly with
5-lipoxygenase or blocking its translocation.

PMID: 8510458 [PubMed - indexed for MEDLINE]

311: Biol Pharm Bull. 1993 Mar;16(3):235-8.

Arabinogalactan core structure and immunological activities of ukonan C, an
acidic polysaccharide from the rhizome of Curcuma longa.

Gonda R, Tomoda M, Ohara N, Takada K.

Kyoritsu College of Pharmacy, Tokyo, Japan.

Controlled Smith degradation of ukonan C, a phagocytosis-activating
polysaccharide isolated from the rhizome of Curcuma longa L., was performed. The
reticuloendothelial system-potentiating, anti-complementary and alkaline
phosphatase-inducing activities of ukonan C and its degradation products were
investigated. Methylation analyses of the primary and secondary Smith
degradation products and of a de-arabinosylated product indicated that
structural features of the arabinogalactan core of ukonan C include a backbone
chain composed of beta-1,3-linked D-galactose and beta-1,4-linked D-xylose. All
of the galactose units in the backbone carry side chains composed of
beta-1,6-linked D-galactosyl residues with or without terminal alpha-L-arabinose
units at position 3. Ukonan C showed remarkable effects on both
reticuloendothelial system-potentiating and alkaline phosphatase-inducing
activities. Periodate oxidation caused a decrease in or disappearance of the
immunological activities, but the controlled Smith degradation product having
the arabinogalactan core structure of polysaccharide showed a pronounced effect
on anti-complementary activity.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 8364466 [PubMed - indexed for MEDLINE]

312: Eur J Pharmacol. 1992 Oct 20;221(2-3):381-4.

Inhibitory effect of curcumin, an anti-inflammatory agent, on vascular smooth
muscle cell proliferation.

Huang HC, Jan TR, Yeh SF.

Department of Pharmacology, College of Medicine, National Taiwan University,
Taipei.

The effects of curcumin, an anti-inflammatory agent from Curcuma longa, on the
proliferation of blood mononuclear cells and vascular smooth muscle cells were
studied. Proliferative responses were determined from the uptake of tritiated
thymidine. In human peripheral blood mononuclear cells, curcumin dose
dependently inhibited the responses to phytohemagglutinin and mixed lymphocyte
reaction at the dose ranges of 10(-6) to 3 x 10(-5) and 3 x 10(-6) to 3 x 10(-5)
M, respectively. Curcumin (10(-6) to 10(-4) M) dose dependently inhibited the
proliferation of rabbit vascular smooth muscle cells stimulated by fetal calf
serum. Curcumin had a greater inhibitory effect on platelet-derived growth
factor-stimulated proliferation than on serum-stimulated proliferation. Cinnamic
acid, coumaric acid and ferulic acid were much less effective than curcumin as
inhibitors of serum-induced smooth muscle cell proliferation, suggesting that
the cinnamic acid and ferulic acid moieties alone are not sufficient for
activity, and that the characteristics of the diferuloylmethane molecule itself
are necessary for activity. Curcumin may be useful as a new template for the
development of better remedies for the prevention of the pathological changes of
atherosclerosis and restenosis.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 1426014 [PubMed - indexed for MEDLINE]

313: Toxicon. 1992 Oct;30(10):1211-8.

Erratum in:
Toxicon 1992 Dec;30(12):1637.

Antivenom and biological effects of ar-turmerone isolated from Curcuma longa
(Zingiberaceae)

Ferreira LA, Henriques OB, Andreoni AA, Vital GR, Campos MM, Habermehl GG, de
Moraes VL.

Departamento de Bioquimica, Instituto Butantan, Sao Paulo, Brazil.

A potent antivenom against snakebite was isolated from Curcuma longa, a plant
commonly used in traditional Brazilian medicine. The fraction consisting of
ar-turmerone neutralized both the hemorrhagic activity present in Bothrops
jararaca venom, and the lethal effect of Crotalus durissus terrificus venom in
mice. Immunological studies demonstrated that this fraction also inhibited the
proliferation and the natural killer activity of human lymphocytes.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't

PMID: 1440627 [PubMed - indexed for MEDLINE]

314: Cancer Lett. 1992 Sep 30;66(2):115-21.

Reversal of aflatoxin induced liver damage by turmeric and curcumin.

Soni KB, Rajan A, Kuttan R.

Amala Cancer Research Centre, Trichur, Kerala State, India.

The effect of certain food additives on aflatoxin production by Aspergillus
parasiticus has been studied in vitro. Extracts of turmeric (Curcuma longa),
garlic (Allium sativum) and asafoetida (Ferula asafoetida) inhibited the
aflatoxin production considerably (more than 90%) at concentrations of 5-10
mg/ml. Similar results were also seen using butylated hydroxytoluene, butylated
hydroxyanisole and ellagic acid at concentration 0.1 mM. Curcumin, the
antioxidant principle from Curcuma longa did not have any effect on aflatoxin
production. Turmeric and curcumin were also found to reverse the aflatoxin
induced liver damage produced by feeding aflatoxin B1 (AFB1) (5 micrograms/day
per 14 days) to ducklings. Fatty changes, necrosis and biliary hyperplasia
produced by AFB1 were considerably reversed by these food additives.

PMID: 1394115 [PubMed - indexed for MEDLINE]

315: Zhongguo Zhong Yao Za Zhi. 1992 Jul;17(7):397-400, 444.

[Growth regularities of yujin (Curcuma longa L.)]

[Article in Chinese]

Wu H, Yang H, Yin G, Chen S.

Sichuan Institute of Chinese Materia Medica, Chongqing.

Based on the characteristics of leaf, root and tuber growth as well as dry
matter accumulation, the ontogeny of Yujin is divided into 4 stages. The growth
and correlation among the leaf, root and tuber as well as accumulation of
essential oils and curcumins have also been studied.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't

PMID: 1445642 [PubMed - indexed for MEDLINE]

316: Arzneimittelforschung. 1992 Jul;42(7):962-4.

Induction of glutathione S-transferase activity by curcumin in mice.

Susan M, Rao MN.

Department of Pharmaceutical Chemistry, College of Pharmaceutical Sciences,
Manipal, India.

Curcumin, a natural constituent of Curcuma longa (turmeric, CAS 458-37-7), has
been studied for its induction of glutathione S-transferase activity in mice. At
a dose of 250 mg/kg orally for 15 days, the enzyme activity in liver was
increased by 1.8 fold. Its effect on other tissues like stomach, small
intestine, lungs, kidney was not significant. Curcumin also depleted sulfhydryl
levels in tissues, especially in stomach where 45% depletion was observed.

PMID: 1418063 [PubMed - indexed for MEDLINE]

317: Cancer Lett. 1992 Jun 15;64(2):117-21.

Effect of dietary curcumin and ascorbyl palmitate on azoxymethanol-induced
colonic epithelial cell proliferation and focal areas of dysplasia.

Huang MT, Deschner EE, Newmark HL, Wang ZY, Ferraro TA, Conney AH.

Department of Chemical Biology and Pharmacognosy, College of Pharmacy, Rutgers
University, Piscataway, NJ 08855-0789.

Curcumin, a major yellow pigment of turmeric obtained from powdered rhizomes of
the plant Curcuma longa Linn., is commonly used as a coloring agent in foods,
drugs and cosmetics. Ascorbyl palmitate is a lipid soluble derivative of
ascorbic acid. Both curcumin and ascorbyl palmitate have antioxidant activity
and are potent inhibitors of 12-O-tetradecanoyl-phorbol-13-acetate-induced tumor
promotion in mouse skin. The effects of dietary curcumin and ascorbyl palmitate
on azoxymethanol (AOM)-induced hyperproliferation of colonic epithelial cells
and the incidence of focal areas of dysplasia (FADs) were evaluated in female
CF-1 mice fed an AIN 76A diet. Subcutaneous injections of AOM (10 mg/kg body wt.
once weekly for 6 weeks) caused hyperplasia and the formation of FADs in the
colon. Administration of 2% curcumin in the diet inhibited AOM-induced formation
of FADs while administration of 2% ascorbyl palmitate in the diet did not
demonstrate inhibition. This result suggests that dietary curcumin may inhibit
AOM-induced colonic neoplasia in mice.

Publication Types:
Comparative Study
Research Support, U.S. Gov't, P.H.S.

PMID: 1611594 [PubMed - indexed for MEDLINE]

318: Planta Med. 1992 Apr;58(2):124-7.

Toxicity studies on Alpinia galanga and Curcuma longa.

Qureshi S, Shah AH, Ageel AM.

Research Centre, College of Pharmacy, King Saud University, Riyadh, Saudi
Arabia.

Acute (24 h) and chronic (90 days) oral toxicity studies on the ethanolic
extracts of the rhizomes of Alpinia galanga and Curcuma longa were carried out
in mice. Acute dosages were 0.5, 1.0, and 3 g/kg body weight while the chronic
dosage was 100 mg/kg/day as the extract. All external morphological,
hematological, and spermatogenic changes, in addition to body weight and vital
organ weights were recorded. During this investigation no significant mortality
as compared to the controls was observed. The weight gain in the A. galanga
treated animals was significant as in the control group while the C.
longa-treated animals gained no significant weight after chronic treatment. C.
longa treatment induced significant changes in heart and lungs weights upon
chronic treatment. Hematological studies revealed a significant rise in the RBC
level of A. galanga-treated animals and a significant fall in the WBC and RBC
levels of the C. longa-treated animals as compared to the controls. The gain in
weights of sexual organs and increased sperm motility and sperm counts were
observed in both groups of extract-treated male mice, however, these changes
were highly significant in the A. galanga-treated group. Both extracts failed to
show any spermatotoxic effects.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 1529022 [PubMed - indexed for MEDLINE]

319: Chem Pharm Bull (Tokyo). 1992 Apr;40(4):994-7.

Homeostasis as regulated by activated macrophage. II. LPS of plant origin other
than wheat flour and their concomitant bacteria.

Inagawa H, Nishizawa T, Tsukioka D, Suda T, Chiba Y, Okutomi T, Morikawa A, Soma
GI, Mizuno D.

Biotechnology Research Center, Teikyo University, Kawasaki, Japan.

In order to seek a macrophage-activating substance, lipopolysaccharide (LPS) of
plant origin other than that of wheat flour was surveyed. A large amount of LPS
(10-100 micrograms/g) was detected in Laminaria japonica (kelp), Curcuma longa
(turmeric), Undaria pinnatifida and other substances. Since concomitant bacteria
possibly existing in root of farm products can be considered to contribute to
LPS of plant origin, a count was taken of bacterial cells both dead and alive.
This count revealed that some LPS were derived from concomitant bacteria which
had probably come from root. Few concomitant bacterial cells were found in
seaweed, while stem-root contained enough bacterial cells. Three predominant
bacteria have been isolated and identified; Pantoea agglomerans, Enterobacter
cloacae, and Serratia ficaria. These LPSs were purified and their chemical
compositions were examined. They are similar to that of Escherichia coli except
that their molecular sizes are smaller. Since LPS is non-toxic when taken orally
or percutaneously, these LPSs may also be advantageous in the cure of
intractable diseases.

Publication Types:
Comparative Study

PMID: 1525958 [PubMed - indexed for MEDLINE]

320: Chem Pharm Bull (Tokyo). 1992 Apr;40(4):990-3.

The core structure of ukonan A, a phagocytosis-activating polysaccharide from
the rhizome of Curcuma longa, and immunological activities of degradation
products.

Gonda R, Tomoda M, Takada K, Ohara N, Shimizu N.

Kyoritsu College of Pharmacy, Tokyo, Japan.

The controlled Smith degradation of ukonan A, a phagocytosis-activating
polysaccharide isolated from the rhizome of Curcuma longa L., was performed. The
reticuloendothelial system-potentiating, anti-complementary and alkaline
phosphatase-inducing activities of ukonan A and its degradation products were
investigated. Methylation analyses of both the primary and the secondary Smith
degradation products indicated that the core structural features of ukonan A
include a backbone chain mainly composed of beta-1,3-linked D-galactose,
beta-1,4-linked D-xylose and alpha-1,2-linked L-rhamnose residues. All of the
galactose units in the backbone carry side chains composed of
alpha-L-arabino-beta-D-galactosyl or beta-D-galactosyl residues at position 6.
Ukonan A has a remarkable effect on each of the three kinds of immunological
activities. Periodate oxidation caused pronounced decrease or disappearance of
the activities, but the controlled Smith degradation product having the core
structure of polysaccharide showed considerable restoration of these activities.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 1525957 [PubMed - indexed for MEDLINE]

321: Arch Biochem Biophys. 1992 Feb 1;292(2):617-23.

Turmerin: a water soluble antioxidant peptide from turmeric [Curcuma longa]

Srinivas L, Shalini VK, Shylaja M.

Department of Nutrition and Food Safety, Central Food Technological Research
Institute, Karnataka State, India.

Dietary spice components have been screened for their protective effect against
reactive oxygen species (ROS)-induced, lipid peroxide-mediated membrane and DNA
damage and mutagenecity. A new, water soluble, 5-kDa peptide--Turmerin--from
turmeric (Curcuma longa) has been found to be an efficient
antioxidant/DNA-protectant/antimutagen. Turmerin forms 0.1% of the dry weight of
turmeric and is obtained in a crystalline form. It is a heat stable, noncyclic
peptide containing 40 amino acid residues, with a blocked N-terminal and leucine
at the C-terminal. It is insensitive to trypsin and pepsin, heat, and uv
radiation. Turmerin contains three residues of methionine which are partly
responsible for the antioxidant activity. Turmerin at 183 nM offers 80%
protection to membranes and DNA against oxidative injury. ROS-induced
arachidonate release and the mutagenic activity of t-butyl hydroperoxide are
substantially inhibited by Turmerin. Tumerin is noncytotoxic up to milligram
concentrations, as tested by Ames assay and in human lymphocytes.

PMID: 1731625 [PubMed - indexed for MEDLINE]

322: J Cancer Res Clin Oncol. 1992;118(6):447-52.

Protective role of aqueous turmeric extract against mutagenicity of
direct-acting carcinogens as well as benzo [alpha] pyrene-induced genotoxicity
and carcinogenicity.

Azuine MA, Kayal JJ, Bhide SV.

Carcinogenesis Division, Tata Memorial Centre, Parel, Bombay, India.

Turmeric (Curcuma longa Linn.) has been shown to inhibit chemical
carcinogenesis. In this study, we compared the chemopreventive efficacy of an
aqueous turmeric extract (AqTE) and its constituents, curcumin-free aqueous
turmeric extract (CFAqTE) and curcumin, using the Salmonella typhimurium
mutagenicity assay and the bone marrow micronucleus test in female Swiss mice.
AqTE exhibited antimutagenic activity against direct-acting mutagens,
4-nitro-O-phenylenediamine and 1-methyl-3-nitro-1-nitrosoguanidine, in strains
TA 98 and TA 100 respectively. Both AqTE and CFAqTE inhibited the mutagenicity
of benzo [alpha]pyrene in the two strains in the presence of
Aroclor-1254-induced rat liver homogenate. The inhibition in both studies was
dose-dependent. Administration of AqTE, CFAqTE and curcumin at a dose of 3
mg/animal 18 h prior to i.p. benzo [alpha]pyrene injection (250 mg/kg)
significantly inhibited bone marrow micronuclei formation in female Swiss mice
by 43%, 76%, and 65% respectively. Furthermore, the incidence and multiplicity
of forestomach tumours induced by benzo [alpha]pyrene (1 mg/animal, twice
weekly, p.o. for 4 weeks) in female Swiss mice were significantly inhibited by
AqTE, CFAqTE and curcumin given 2 weeks before, during and after the carcinogen
treatment. These data indicate that the protection against genomic damage by
turmeric extract and its components tested could be necessary for some aspects
of its cancer chemoprevention.

PMID: 1618892 [PubMed - indexed for MEDLINE]

323: Chem Pharm Bull (Tokyo). 1992 Jan;40(1):185-8.

Characterization of a neutral polysaccharide having activity on the
reticuloendothelial system from the rhizome of Curcuma longa.

Gonda R, Takeda K, Shimizu N, Tomoda M.

Kyoritsu College of Pharmacy, Tokyo, Japan.

A neutral polysaccharide, named ukonan D, was isolated from the rhizome of
Curcuma longa L. It produced a single band on electrophoresis and a single peak
on gel chromatography, and its molecular mass was estimated to be 28,000. It
showed remarkable reticuloendothelial system-potentiating activity in a carbon
clearance test. Ukonan D is composed of L-arabinose: D-galactose: D-glucose:
D-mannose in the molar ratio of 1:1:12:0.2, in addition to small amounts of
peptide moiety. Methylation analysis, carbon-13 nuclear magnetic resonance and
enzymic degradation studies indicated that its structural features include
mainly both alpha-1,5-linked L-arabino-beta-3,6-branched D-galactan type and
alpha-4,6-branched D-glucan type structural units. The influence of degradation
with alpha-amylase followed by the elimination of glucan side chains on its
immunological activity was discussed.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't

PMID: 1576672 [PubMed - indexed for MEDLINE]

324: Trop Geogr Med. 1992 Jan;44(1-2):178-81.

The use and efficacy of Azadirachta indica ADR ('Neem') and Curcuma longa
('Turmeric') in scabies. A pilot study.

Charles V, Charles SX.

Medical and Cancer Research and Treatment Centre, Nagercoil, India.

In the Ayurvedha and Sidha system of medicine (Indian system of medicine)
Azadirachta indica ADR ('Neem') and Curcuma longa ('Turmeric') has been used for
healing chronic ulcers and scabies. The 'Neem' and 'Turmeric' was used as a
paste for the treatment of scabies in 814 people. In 97% of cases cure was
obtained within 3 to 15 days of treatment. We find that this is a very cheap,
easily available, effective and acceptable mode of treatment for the villagers
in the developing countries. We have noticed no toxic or adverse reaction so
far. However, further research is needed.

PMID: 1496714 [PubMed - indexed for MEDLINE]

325: Zhongguo Zhong Yao Za Zhi. 1991 Oct;16(10):590-2, 639.

[High-yield agronomic measures of Curcuma longa L.]

[Article in Chinese]

Wu H, Li L, Yang H, Chen S.

Sichuan Institute of Chinese Materia Medica, Chongqing.

A method of orthogonal conic combinatorial design has been employed in the study
of high-yield agronomic measures of C. longa. The results show that by
increasing plants/mu and postponing sowing date, the yield is 50% higher than
before, mathematical model of yield on plants/mu and sowing date were
established, which can be used to predict the yield and explore optimal
agronomic measures.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't

PMID: 1820789 [PubMed - indexed for MEDLINE]

326: Food Chem Toxicol. 1991 Oct;29(10):699-706.

Turmeric (Curcuma longa)-induced reduction in urinary mutagens.

Polasa K, Sesikaran B, Krishna TP, Krishnaswamy K.

National Institute of Nutrition, Jamai-Osmania, Hyderabad, A.P., India.

Rats were fed turmeric at various levels in the diet for up to 3 months and then
exposed to benzo[a]pyrene (B[a]P) or 3-methylcholanthrene (3-MC) by ip
injection. Urinary mutagens were detected using the Salmonella typhimurium
assay. Turmeric fed at 0.5% and above inhibited B[a]P- and 3-MC-mediated
mutagenicity. Turmeric did not adversely affect the food intake, or weight gain
of the rats and no histological changes were detected. These findings are
significant in view of the widespread exposure of humans to polycyclic aromatic
hydrocarbons. The study has also revealed a useful in vivo model for testing the
antimutagenicity.

PMID: 1660015 [PubMed - indexed for MEDLINE]

327: J Ethnopharmacol. 1991 May-Jun;33(1-2):91-5.

Treatment of osteoarthritis with a herbomineral formulation: a double-blind,
placebo-controlled, cross-over study.

Kulkarni RR, Patki PS, Jog VP, Gandage SG, Patwardhan B.

Bryamjee Jeejeebhoy Medical College, University of Poona, Pune, India.

The clinical efficacy of a herbomineral formulation containing roots of Withania
somnifera, the stem of Boswellia serrata, rhizomes of Curcuma longa and a zinc
complex (Articulin-F), was evaluated in a randomized, double-blind, placebo
controlled, cross-over study in patients with osteoarthritis. After a one-month
single blind run-in period, 42 patients with osteoarthritis were randomly
allocated to receive either a drug treatment or a matching placebo for a period
of three months. After a 15-day wash-out period the patients were transferred to
the other treatment for a further period of three months. Clinical efficacy was
evaluated every fortnight on the basis of severity of pain, morning stiffness,
Ritchie articular index, joint score, disability score and grip strength. Other
parameters like erythrocyte sedimentation rate and radiological examination were
carried out on a monthly basis. Treatment with the herbomineral formulation
produced a significant drop in severity of pain (P less than 0.001) and
disability score (P less than 0.05). Radiological assessment, however, did not
show any significant changes in both the groups. Side effects observed with this
formulation did not necessitate withdrawal of treatment.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 1943180 [PubMed - indexed for MEDLINE]

328: Planta Med. 1991 Feb;57(1):1-7.

Pharmacology of Curcuma longa.

Ammon HP, Wahl MA.

Department of Pharmacology, Eberhard-Karls-Universitat Tubingen, Federal
Republic of Germany.

The data reviewed indicate that extracts of Curcuma longa exhibit
anti-inflammatory activity after parenteral application in standard animal
models used for testing anti-inflammatory activity. It turned out that curcumin
and the volatile oil are at least in part responsible for this action. It
appears that when given orally, curcumin is far less active than after i.p.
administration. This may be due to poor absorption, as discussed. Data on
histamine-induced ulcers are controversial, and studies on the secretory
activity (HCl, pepsinogen) are still lacking. In vitro, curcumin exhibited
antispasmodic activity. Since there was a protective effect of extracts of
Curcuma longa on the liver and a stimulation of bile secretion in animals,
Curcuma longa has been advocated for use in liver disorders. Evidence for an
effect on liver disease in humans is not yet available. From the facts that
after oral application only traces of curcumin were found in the blood and that,
on the other hand, most of the curcumin is excreted via the faeces it may be
concluded that curcumin is absorbed poorly by the gastrointestinal tract and/or
underlies presystemic transformation. Systemic effects therefore seem to be
questionable after oral application except that they occur at very low
concentrations of curcumin. This does not exclude a local action in the
gastrointestinal tract.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 2062949 [PubMed - indexed for MEDLINE]

329: Biochem Pharmacol. 1990 Jun 15;39(12):1869-75.

Cytotoxic and cytoprotective activities of curcumin. Effects on
paracetamol-induced cytotoxicity, lipid peroxidation and glutathione depletion
in rat hepatocytes.

Donatus IA, Sardjoko, Vermeulen NP.

Department of Pharmacochemistry, Free University, Amsterdam, The Netherlands.

The cytoprotective effect of curcumin, a natural constituent of Curcuma longa,
on the cytotoxicity of paracetamol in rat hepatocytes was studied. Paracetamol
was selected as a model-toxin, since it is known to be bioactivated by
3-methylcholanthrene inducible cytochromes P450 presumably to
N-acetyl-p-benzoquinone imine (NAPQI), a reactive metabolite which upon
overdosage causes protein- and non-protein thiol-depletion, lipid peroxidation
and cytotoxicity measured as LDH-leakage. At low concentrations curcumin was
found to protect significantly against paracetamol-induced lipid peroxidation,
without protection against paracetamol-induced LDH-leakage and without
protection against paracetamol-induced GSH-depletion. At a 100 times higher
concentration of curcumin the observed protective effect on lipid peroxidation
was accompanied with a tendency to increase cellular GSH-depletion and
LDH-leakage. No time-dependency was found as to the curcumin-induced effects:
treatment of the hepatocytes 1 hr before, concomitantly or 1 hr after the
addition of paracetamol to the cells had similar effects. In contrast to what
was expected on the basis of previous in vivo experiments, at higher
concentrations curcumin itself was found to be slightly cytotoxic.
Curcumin-induced LDH-leakage was accompanied by a significant depletion of GSH.
It has been concluded that the observed cytoprotective and cytotoxic activities
of curcumin may be explained by a strong anti-oxidant capacity of curcumin and
the capability of curcumin to conjugate with GSH. Furthermore, it has been
concluded that lipid peroxidation is not playing a causal role in cell-death
induced by paracetamol or by curcumin.

PMID: 2353930 [PubMed - indexed for MEDLINE]

330: Mol Cell Biochem. 1990 Jun 1;95(1):21-30.

Fuel smoke condensate induced DNA damage in human lymphocytes and protection by
turmeric (Curcuma longa).

Shalini VK, Srinivas L.

Department of Nutrition and Food Safety, Central Food Technological Research
Institute, Mysore, India.

Twigs-dry leaves smoke condensate (TDS) was investigated for its DNA damaging
activity in human peripheral lymphocytes, by using a sensitive method,
fluorescence analysis of DNA unwinding (FADU). An aqueous turmeric component
(Aq.T) was studied as a protective agent. TDS at one to 100 folds dilution
induced 55% DNA damage at 20 min, while 12-O-tetradecanoylphorbol-13-acetate
(TPA) at 10 ng/ml induced only 25% damage. Aq.T at 300 ng/microliter afforded
90% protection to DNA against TDS and 65% against TPA. The mechanism of Aq.T
protection was investigated by using (i) inhibitors of arachidonate cascade,
viz., indomethacin (28 microM), NDGA (10 microM), DBAP (36 microM), (ii)
antioxidant enzymes viz., CAT (0.2 U/microliter), SOD (0.6 U/microliter), (iii)
antioxidants--BHA, curcumin (40 microM), mixed gangliosides (20 nM) and protease
inhibitor TLCK (100 microM). These compounds offered the following extents of
protection to DNA against TDS: indomethacin--40%, NDGA--83%, DBAP--70%,
SOD--38%, CAT--40%, BHA--38%, curcumin--60%, mixed gangliosides--88%, TLCK--85%.
Against TPA as clastogenic agent, the extents of protection were:
indomethacin--73%, NDGA--32%, DBAP--72%, SOD--60%, CAT, BHA-negligible,
curcumin--23%, mixed gangliosides--60%, TLCK--59%. These results indicate that
(i) TDS and TPA induce DNA damage possibly by different mechanisms, (ii) Aq.T is
a more effective protectant against TDS whereas it is on par with other
inhibitors against TPA.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 2366750 [PubMed - indexed for MEDLINE]

331: J Ethnopharmacol. 1990 Apr;29(1):25-34.

Evaluation of turmeric (Curcuma longa) for gastric and duodenal antiulcer
activity in rats.

Rafatullah S, Tariq M, Al-Yahya MA, Mossa JS, Ageel AM.

Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy,
King Saud University, Riyadh, Saudi Arabia.

An ethanol extract of turmeric was studied in rats for its ability to inhibit
gastric secretion and to protect gastroduodenal mucosa against the injuries
caused by pyloric ligation, hypothermic-restraint stress, indomethacin,
reserpine and cysteamine administration and cystodestructive agents including
80% ethanol, 0.6 M HCl, 0.2 M NaOH and 25% NaCl. An oral dose of 500 mg/kg of
the extract produced significant anti-ulcerogenic activity in rats subjected to
hypothermic-restraint stress, pyloruic ligation and indomethacin and reserpine
administration. The extract had a highly significant protective effect against
cystodestructive agents. The reduction in the intensity of ulceration of
cysteamine-induced duodenal ulcers was not found to be statistically
significant. Turmeric extract not only increased the gastric wall mucus
significantly but also restored the non-protein sulfhydryl (NP-SH) content in
the glandular stomachs of the rats.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 2345457 [PubMed - indexed for MEDLINE]

332: Chem Pharm Bull (Tokyo). 1990 Feb;38(2):482-6.

Characterization of polysaccharides having activity on the reticuloendothelial
system from the rhizome of Curcuma longa.

Gonda R, Tomoda M, Shimizu N, Kanari M.

Kyoritsu College of Pharmacy, Tokyo, Japan.

Three polysaccharides, named ukonan A, ukonan B and ukonan C, were isolated from
the rhizomes of Curcuma longa L. They were homogeneous on electrophoresis and
gel chromatography, and showed remarkable reticuloendothelial
system-potentiating activity in a carbon clearance test. They are composed of
L-arabinose: D-xylose: D-galactose: D-glucose: L-rhamnose: D-galacturonic acid
in the molar ratios of 12:4:12:1:4:10 (ukonan A), 12:4:12:1:2:4 (ukonan B) and
8:3:6:14:2:3 (ukonan C), in addition to small amounts of peptide moiety.
Methylation analysis, carbon-13 nuclear magnetic resonance and periodate
oxidation studies indicated the structural features of ukonan B, the major one
in terms of the activity. It has acidic arabino-galactan type structural units.

Publication Types:
In Vitro

PMID: 2337962 [PubMed - indexed for MEDLINE]

333: Prostaglandins Leukot Essent Fatty Acids. 1989 Jul;37(1):57-64.

Extracts from two frequently consumed spices--cumin (Cuminum cyminum) and
turmeric (Curcuma longa)--inhibit platelet aggregation and alter eicosanoid
biosynthesis in human blood platelets.

Srivastava KC.

Department of Environmental Medicine, Odense University, Denmark.

In the traditional Indian system of medicine, Ayurveda, several spices and herbs
are claimed to possess medicinal properties, such as being antithrombotic,
antiatherosclerotic, hypolipidemic, anti-inflammatory etc. Earlier we have
reported that extracts from several spices behave as antiaggregatory agents and
inhibit eicosanoid synthesis. Similar studies with extracts prepared from cumin
(Cuminum cyminum) and turmeric (Curcuma longa) were undertaken. Ethereal extract
of both cumin and turmeric inhibited arachidonate-induced platelet aggregation.
Extracts from these spices inhibited thromboxane B2 production from exogenous
(14C) arachidonic acid (AA) in washed platelets; a simultaneous increase in the
formation of lipoxygenase-derived products was observed. Less TxB2 was produced
in blood samples treated with turmeric extract when they were allowed to clot.
Turmeric extract inhibited incorporation of (14C)AA into platelet phospholipids
and deacylation of AA-labelled phospholipids on stimulation with calcium
ionophore A23187. Cumin extract was devoid of such effects. Extracts from the
two spices reduced the formation of (14C)TxB2 from AA-labelled platelets when
they were challenged with A23187. The anti-inflammatory property of turmeric
may, in part, be explained by its effect on eicosanoid biosynthesis.

PMID: 2503839 [PubMed - indexed for MEDLINE]

334: Arch Microbiol. 1989;151(2):183-5.

Photokilling of bacteria by the natural dye curcumin.

Dahl TA, McGowan WM, Shand MA, Srinivasan VS.

Center for Photochemical Sciences, Bowling Green State University, OH 43403.

Curcumin is a yellow-orange compound derived from the root of Curcuma longa
(Zingiberaceae family), that has been used as a medicine, spice and coloring
agent. Curcumin has proved nontoxic in a number of cell culture and whole animal
studies. Curcumin has, however, been reported to have bactericidal effects at
very high concentrations. When illuminated, curcumin exerted potent phototoxic
effects in micromolar amounts. Gram-negative bacteria displayed greater
resistance to curcumin phototoxicity relative to Gram-positive bacteria. Oxygen
was required for curcumin phototoxicity. Curcumin binding to cells was not
required for photokilling; the reactive intermediate therefore must be
relatively long-lived. The mechanism(s) of curcumin phototoxicity may involve
hydrogen peroxide production. Singlet excited oxygen was not detected.

PMID: 2655550 [PubMed - indexed for MEDLINE]

335: Indian J Physiol Pharmacol. 1988 Oct-Dec;32(4):299-304.

Hypolipidaemic effects of Curcuma longa L and Nardostachys jatamansi, DC in
triton-induced hyperlipidaemic rats.

Dixit VP, Jain P, Joshi SC.

Department of Zoology, University of Rajasthan, Jaipur.

Fifty per cent ethanolic extract of Curcuma longa (tuber) and Nardostachys
jatamansi (whole plant) feeding elevates HDL-cholesterol/total cholesterol
ratio. The extracts also caused a significant reduction in the ratio of total
cholesterol/phospholipids. Curcuma longa exhibited better cholesterol and
triglyceride lowering activity [Ch = -85%; Tg = -88%] as compared to N.
jatamansi in triton-induced hyperlipidaemic rats. In view of the protective
action of HDL against heart disease and atherogenecity, C. longa consumption is
recommended.

PMID: 3215683 [PubMed - indexed for MEDLINE]

336: Mol Cell Biochem. 1987 Sep;77(1):3-10.

Lipid peroxide induced DNA damage: protection by turmeric (Curcuma longa).

Shalini VK, Srinivas L.

Department of Nutrition and Food Safety, Central Food Technological Research
Institute, Mysore, India.

Liposomal lipid peroxidation and peroxide induced DNA damage were investigated.
Inhibition of lipid peroxidation was studied using 400 microM uric acid,
beta-carotene, alpha-tocopherol, curcumin and butylated hydroxyanisole (BHA).
Curcumin, the active principle of turmeric (Curcuma longa), was as effective an
antioxidant as BHA. An aqueous extract of turmeric was also found to be an
effective inhibitor. The inhibition obtained using this aqueous extract,
incorporated into the liposome itself, was 70% at 300 ng/microliter. This
indicates the presence of yet another antioxidant in turmeric besides the
lipophilic curcumin. The aqueous antioxidant extended 80% protection to DNA
against peroxidative injury at 100 ng/microliter. This component of turmeric is
being characterised and investigated as an antioxidant/anticlastogen and as an
antipromoter.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 3696162 [PubMed - indexed for MEDLINE]

337: Contact Dermatitis. 1987 Sep;17(3):186.

Allergic contact dermatitis to Curcuma longa (turmeric).

Goh CL, Ng SK.

Middle Road Hospital, Singapore.

Publication Types:
Case Reports

PMID: 2960490 [PubMed - indexed for MEDLINE]

338: Food Chem Toxicol. 1987 Jul;25(7):545-7.

In vitro antimutagenicity of curcumin against environmental mutagens.

Nagabhushan M, Amonkar AJ, Bhide SV.

The effects of curcumin, the yellow pigment of the spice, turmeric (Curcuma
longa) on the mutagenicity of several environmental mutagens were investigated
in the Salmonella/microsome test with or without Aroclor 1254-induced rat-liver
homogenate (S-9 mix). With Salmonella typhimurium strain TA98 in the presence of
S-9 mix, curcumin inhibited the mutagenicity of bidi and cigarette smoke
condensates, tobacco and masheri extracts, benzo[a]pyrne and dimethyl
benzo[a]anthracene in a dose-dependent manner. Curcumin did not influence the
mutagenicity without S-9 mix of sodium azide, monoacetylhydrazine and
streptozocin in strain TA100 nor of 4-nitrophenylenediamine in strain TA98. Our
observations indicate that curcumin may alter the metabolic activation and
detoxification of mutagens.

Publication Types:
In Vitro

PMID: 3623345 [PubMed - indexed for MEDLINE]

339: Tumori. 1987 Feb 28;73(1):29-31.

Turmeric and curcumin as topical agents in cancer therapy.

Kuttan R, Sudheeran PC, Josph CD.

An ethanol extract of turmeric ("Curcuma longa") as well as an ointment of
curcumin (its active ingredient) were found to produce remarkable symptomatic
relief in patients with external cancerous lesions. Reduction in smell were
noted in 90% of the cases and reduction in itching in almost all cases. Dry
lesions were observed in 70% of the cases, and a small number of patients (10%)
had a reduction in lesion size and pain. In many patients the effect continued
for several months. An adverse reaction was noticed in only one of the 62
patients evaluated.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 2435036 [PubMed - indexed for MEDLINE]

340: Yao Xue Xue Bao. 1986 May;21(5):382-5.

[Separation and determination of curcuminoids in Curcuma longa L. and its
preparation by HPLC]

[Article in Chinese]

Zhao DY, Yang MK.

Publication Types:
English Abstract

PMID: 3606744 [PubMed - indexed for MEDLINE]

341: Eisei Shikenjo Hokoku. 1986;(104):124-8.

[Studies on the cultivation of turmeric (Curcuma longa L.). I. Varietal
differences in rhizome yield and curcuminoid content]

[Article in Japanese]

Aoi K, Kaburagi K, Seki T, Tobata T, Satake M, Kuroyanagi M.

Publication Types:
English Abstract

PMID: 3567424 [PubMed - indexed for MEDLINE]

342: Cancer Lett. 1985 Nov;29(2):197-202.

Potential anticancer activity of turmeric (Curcuma longa).

Kuttan R, Bhanumathy P, Nirmala K, George MC.

Anticancer activity of the rhizomes of turmeric was evaluated in vitro using
tissue culture methods and in vivo in mice using Dalton's lymphoma cells grown
as ascites form. Turmeric extract inhibited the cell growth in Chinese Hamster
Ovary (CHO) cells at a concentration of 0.4 mg/ml and was cytotoxic to
lymphocytes and Dalton's lymphoma cells at the same concentration. Cytotoxic
effect was found within 30 min at room temperature (30 degrees C). The active
constituent was found to be 'curcumin' which showed cytotoxicity to lymphocytes
and Dalton's lymphoma cells at a concentration of 4 micrograms/ml. Initial
experiments indicated that turmeric extract and curcumin reduced the development
of animal tumours.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 4075289 [PubMed - indexed for MEDLINE]

343: Chem Pharm Bull (Tokyo). 1985 Apr;33(4):1725-8.

Natural antioxidants. III. Antioxidative components isolated from rhizome of
Curcuma longa L.

Toda S, Miyase T, Arichi H, Tanizawa H, Takino Y.

PMID: 4042250 [PubMed - indexed for MEDLINE]

344: Tokai J Exp Clin Med. 1984 Mar;9(1):27-31.

Curcuma longa (Linn) drops in corneal wound healing.

Mehra KS, Mikuni I, Gupta U, Gode KD.

In this study, an attempt has been made to evaluate the cortisone like
inhibitory activity on healing of wounds of curcuma longa extracts-aqueous
extract (2.8%) and alcoholic extract (1.125%) on the healing of superficial and
penetrating corneal wounds in albino rabbits. It was observed that curcuma longa
aqueous drops (a) definitely delayed healing of superficial corneal wounds (P
less than 0.001), (b) delayed healing of penetrating corneal wounds also and
markedly reduced the tensile strength of corneal wounds (P less than 0.02), when
comparison was made with placebo and preservative drops.

PMID: 6535298 [PubMed - indexed for MEDLINE]

345: Planta Med. 1983 Nov;49(3):185-7.

Antihepatotoxic principles of Curcuma longa rhizomes.

Kiso Y, Suzuki Y, Watanabe N, Oshima Y, Hikino H.

Publication Types:
In Vitro

PMID: 6657788 [PubMed - indexed for MEDLINE]

346: Gastroenterology. 1983 Jun;84(6):1578-84.

Effect of 1-phenylpentanol on release of secretin and exocrine pancreatic
secretion in dogs and humans.

Chey WY, Millikan L, Lee KY, Watanabe S, Shiratori K, Takeuchi T.

1-Phenyl-1-hydroxy-N-pentane is a synthetic derivative of an ingredient of
Curcuma longa that is used as a condiment and dye. The effects of 1-phenyl-1-
hydroxy-N-pentane on release of secretin, gastrin, and pancreatic secretion of
bicarbonate and protein were studied in both dogs and humans. In fasting dogs
with gastric fistulas and modified Herrera's pancreatic fistulas, intraduodenal
administration of 1-phenyl-1-hydroxy-N-pentane (pH 6.7) in three different doses
(25, 50, and 100 mg/kg) resulted in significant increases in both plasma
secretin concentration and bicarbonate output. The increases in the two
variables were dose related. The bicarbonate output and plasma secretin
concentration produced by the doses of 1-phenyl-1-hydroxy-N-pentane correlated
well. No significant change occurred in either protein output or plasma gastrin
concentration. The effect of intragastric 1-phenyl-1-hydroxy-N-pentane on
release of secretin and pancreatic secretion was also studied in the digestive
state. While gastric pH was maintained at 5.5 by intragastric titration with 1 N
NaOH after intragastric administration of 5% liver extract solution,
intragastric administration of 1-phenyl-1-hydroxy-N-pentane (100 mg/kg) resulted
in significant increases in both plasma secretin concentrations and pancreatic
bicarbonate output. In the same experiment, the plasma gastrin concentration did
not change significantly, whereas gastric acid secretion decreased significantly
after the 1-phenyl-1-hydroxy-N-pentane administration. In 6 human volunteers,
both plasma secretin concentration and pancreatic bicarbonate output
significantly increased when 2% 1-phenyl-1-hydroxy-N-pentane solution, 30 ml/30
min, was infused in the upper jejunum. Again, no increase in the protein output
was apparent. These studies indicate that endogenous secretin is released by an
agent other than acid and suggest strongly that the increased pancreatic
bicarbonate secretion is attributed to the increased plasma concentration of
secretin. 1-Phenyl-1-hydroxy-N-pentane may be a useful agent for release of
secretin in subjects with achlorhydria, severe hyposecretory state, or total
gastrectomy.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

PMID: 6840488 [PubMed - indexed for MEDLINE]

347: Zhong Yao Tong Bao. 1983 Jan;8(1):27-9.

[Studies on Chinese Curcuma. III. Comparison of the volatile oil and phenolic
constituents from rhizome and tuber of Curcuma longa]

[Article in Chinese]

Chen YH.

PMID: 6235008 [PubMed - indexed for MEDLINE]

348: Zhong Yao Tong Bao. 1983 Jan;8(1):27-9.

[Studies on Chinese Curcuma. III. Comparison of the volatile oil and phenolic
constituents from the rhizoma and the tuber of Curcuma longa]

[Article in Chinese]

Chen YH.

PMID: 6220833 [PubMed - indexed for MEDLINE]

349: Indian J Exp Biol. 1980 Jan;18(1):73-5.

Toxicity studies on turmeric (Curcuma longa): acute toxicity studies in rats,
guineapigs & monkeys.

Shankar TN, Shantha NV, Ramesh HP, Murthy IA, Murthy VS.

PMID: 6772551 [PubMed - indexed for MEDLINE]

350: Indian J Exp Biol. 1979 Dec;17(12):1363-6.

Effect of turmeric (Curcuma longa) fractions on the growth of some intestinal &
pathogenic bacteria in vitro.

Bhavani Shankar TN, Sreenivasa Murthy V.

PMID: 540987 [PubMed - indexed for MEDLINE]

351: Indian J Med Res. 1978 Nov;68:864-6.

Antimicrobial efficacy of the essential oil of Curcuma longa.

Banerjee A, Nigam SS.

PMID: 730260 [PubMed - indexed for MEDLINE]

352: Z Allg Mikrobiol. 1977;17(8):617-22.

Effect of a new fluorochrome on pre- and post-UV treatment of Taphrina maculans
Butler.

Singh UP, Nagai S.

Taphrin maculans BUTLER incites leaf spots disease in turmeric (Curcuma longa
L.) plants. The pathogen forms two types of colonies namely, salmon-red and and
creamy-white in the artificial medium when isolated from a single infection
spot. Both strains resemble yeasts in morphology. The two strains were subjected
to UV irradiation. The salmon-red one showed higher resistance to UV than the
white one, presumably due to the presence of a red pigment in the former. When
spores of the salmon-red strain were pre-treated with a new fluorochrome HOECHST
33258 the survival decreased. Decreased survival of the salmon-red strain was
also observed during post-treatment which is probably due to the combined effect
of UV and dye. The creamy-white strain differs from the salmon-red one in UV
sensitivity, and also during combined treatment with UV and dye. During
pre-treatment the organism shows more survival than during post-treatment with
the fluorochrome. This differential response is discussed in the light of repair
mechanisms involved in the organism.

PMID: 610063 [PubMed - indexed for MEDLINE]

353: Indian J Med Res. 1976 Apr;64(4):601-8.

Comparison of anti-inflammatory activity of various extracts of Curcuma longa
(Linn).

Yegnanarayan R, Saraf AP, Balwani JH.

Publication Types:
Comparative Study

PMID: 965061 [PubMed - indexed for MEDLINE]

354: Planta Med. 1974 Nov;26(3):225-7.

Effect of Curcuma longa (rhizomes) on fertility in experimental animals.

Garg SK.

PMID: 4427957 [PubMed - indexed for MEDLINE]

355: Planta Med. 1974 Aug;26(1):9-19.

[Effect of an alcohol extract and of active ingredients from Curcuma longa on
bacteria and fungi (author's transl)]

[Article in German]

Lutomski J, Kedzia B, Debska W.

Publication Types:
English Abstract

PMID: 4848567 [PubMed - indexed for MEDLINE]

356: Indian J Med Res. 1972 Jan;60(1):138-42.

Anti-inflammatory and anti-arthritic activity of volatile oil of Curcuma longa
(Haldi).

Chandra D, Gupta SS.

PMID: 5029117 [PubMed - indexed for MEDLINE]

357: Indian J Med Res. 1971 Aug;59(8):1289-95.

Anti-inflammatory studies on Curcuma longa (turmeric).

Arora RB, Kapoor V, Basu N, Jain AP.

PMID: 5132235 [PubMed - indexed for MEDLINE]

358: J Pharm Pharmacol. 1953 Jul;5(7):448-57.

A chromatographic study of the curcuminoids in Curcuma longa, L.

SRINIVASAN KR.

PMID: 13070173 [PubMed - indexed for MEDLINE]

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