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, paribalaji@gmail.com.
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.
olatunde_farombi@yahoo.com
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.
mursradhika@yahoo.co.in
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. chengyang@smmail.com
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. trini@uvic.ca.
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. spelman123@earthlink.net.
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. vanielango@yahoo.com
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. immunpym@pusan.ac.kr
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. ipseetamohanty@yahoo.co.in
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. nabeelkhouri@yahoo.com
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 d
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