Clinical Studies

Abstracts are presented below for clinical studies on Indian Barberry.

• Botanical Name: Berberis Aristata

• Ayurvedic Name: Daruharidra

• Common Name: Indian Barberry

Plant Phytonutrient Profile

1: Environ Monit Assess. 2006 May;116(1/​3):315/​20.

Estimation of heavy metals in different berberis species and its market samples.

Srivastava SK, Rai V, Srivastava M, Rawat AK, Mehrotra S.

Pharmacognosy and Ethnopharmacology Division, National Botanical Research
Institute, Lucknow, 226001, India. pharmacognosy1@rediffmail.com

Popularity of herbal drugs is increasing all over the world because of lesser
side effects as compared to synthetic drugs. Besides, it costs less and easily
available to poor people particularly in developing countries. But quality
assurance of herbal drugs is very necessary prior to its use. Because in today's
polluted environment, even herbal drugs are not safe. Berberis spp. is very
important medicinal plant, having various medicinal properties. It is also
included in Indian and British pharmacopoeias. Its demand is quite high in
herbal drug market. So, to check the quality of market samples of this drug, ten
different samples were procured from different drug markets of India for heavy
metal estimation. Besides, genuine samples of four species of Berberis viz. B.
aristata, B. chitria, B. lycium, B. asiatica were also collected from natural
habitats to compare heavy metal concentration in both market and genuine
samples. It was found that market samples were much more contaminated than
genuine samples. Lead (Pb) concentration is far beyond from WHO permissible
limit (10 ppm) for herbal drugs, reaching to maximum 49.75 ppm in Amritsar
market sample. Likewise, concentration of all other metals like Cd, Cr and Ni
were also very high in market samples as compared to genuine samples.

Publication Types:
Comparative Study

PMID: 16779598 [PubMed /​ indexed for MEDLINE]

2: 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]

3: Drug Metab Dispos. 2004 Apr;32(4):405/​12.

Hepatobiliary excretion of berberine.

Tsai PL, Tsai TH.

National Research Institute of Chinese Medicine, 155/​1, Li/​Nong Street Section
2, Shih/​Pai, Taipei 112, Taiwan. thtsai@cma23.nricm.edu.tw

Berberine is a bioactive herbal ingredient isolated from the roots and bark of
Berberis aristata or Coptis chinensis. To investigate the detailed
pharmacokinetics of berberine and its mechanisms of hepatobiliary excretion, an
in vivo microdialysis coupled with high/​performance liquid chromatography was
performed. In the control group, rats received berberine alone; in the
drug/​treated group, 10 min before berberine administration, the rats were
injected with cyclosporin A (CsA), a P/​glycoprotein (P/​gp) inhibitor; quinidine,
both organic cation transport (OCT) and P/​gp inhibitors; SKF/​525A (proadifen), a
cytochrome P450 inhibitor; and probenecid to inhibit the glucuronidation. The
results indicate that berberine displays a linear pharmacokinetic phenomenon in
the dosage range from 10 to 20 mg kg(/​1), since a proportional increase in the
area under the concentration/​time curve (AUC) of berberine was observed in this
dosage range. Moreover, berberine was processed through hepatobiliary excretion
against a concentration gradient based on the bile/​to/​blood distribution ratio
(AUC(bile)/AUC(blood)); the active berberine efflux might be affected by P/​gp
and OCT since coadministration of berberine and CsA or quinidine at the same
dosage of 10 mg kg(/​1) significantly decreased the berberine amount in bile. In
addition, berberine was metabolized in the liver with phase I demethylation and
phase II glucuronidation, as identified by liquid chromatography/tandem mass
spectrometry. Also, the phase I metabolism of berberine was partially reduced by
SKF/​525A treatment, but the phase II glucuronidation of berberine was not
obviously affected by probenecid under the present study design.

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

PMID: 15039293 [PubMed /​ indexed for MEDLINE]

4: J AOAC Int. 2003 Nov/​Dec;86(6):1124/​7.

Spectrophotometric method for estimation of alkaloids precipitable with
Dragendorff's reagent in plant materials.

Sreevidya N, Mehrotra S.

National Botanical Research Institute, 2, Rana Pratap Marg, Lucknow, India 226
001.

A rapid, easy, and simple spectrophotometric method was developed for the
estimation of total alkaloids precipitated by Dragendorff's reagent (DR) in
plant materials. It is based on the formation of yellow bismuth complex in
nitric acid medium with thiourea. The yellow/​colored complex formed obeys
Lambert/​Beer's law in the concentration range of 0.06/​50 microg/mL with
lambdamax at 435 nm. Using this method, the alkaloidal percentage of certain
alkaloids (ajamalicine, papaverine, cinchonine, piperine, berberine) and some
plant materials containing alkaloids (Berberis aristata, Solanum nigrum, and
Piper longum) were determined. The method was compared with other methods. It
can be used for routine analysis of commercial samples by industries dealing
with herbal drugs for standardization of plant materials containing alkaloids
and for alkaloid/​containing pharmaceutical products.

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

PMID: 14979692 [PubMed /​ indexed for MEDLINE]

5: Indian J Exp Biol. 2001 Dec;39(12):1308/​10.

An experimental study of some indigenous drugs with special reference to
hydraulic permeability.

Upadhyay L, Mehrotra A, Srivastava AK, Rai NP, Tripathi K.

Department of Medicine, Institute of Medical Sciences, Banaras Hindu University,
Varanasi, India.

The effect of commonly used indigenous drugs for hepatic disorders i.e.
Tinospora cordifolia, (Guduchi/Amrita), Andrographis paniculata (Kalmegha),
Picrorhiza kurroa (Kutki), Phyllantnus niruri (Bhoomyamalaki) and Berberis
aristata (Daruharidra) was tested on the hydraulic permeability of water in the
presence of bile salt through a transport cell model. The data on hydraulic
permeability were calculated as t (time). JV = Lp x AP, where Lp = hydraulic
conductivity and AP is the pressure difference. It was observed that the value
of controlled hydraulic permeability (0.49 x 10(/​8) M3 S(/​1) N(/​1)) decreased in
the presence of indigenous drugs and bile salt. The results suggest that these
drugs might have the cell membrane stabilizing property which may lead to
prevention of the toxic effect of bile salts in various hepatic disorders.

PMID: 12018531 [PubMed /​ indexed for MEDLINE]

6: J Egypt Soc Parasitol. 2001 Dec;31(3):893/​904 + 1p plate.

Evaluation of the effect of a plant alkaloid (berberine derived from Berberis
aristata) on Trichomonas vaginalis in vitro.

Soffar SA, Metwali DM, Abdel/​Aziz SS, el/​Wakil HS, Saad GA.

Department of Parasitology, Faculty of Medicine, Ain Shams University, Cairo,
Egypt.

Berberine is a quaternary alkaloid derived from the plant Berberis aristata
having antibacterial, antiamoebic, antifungal, antihelminthic, leishmanicidal
and tuberculostatic properties. The effect of berberine sulphate salt on the
growth of Trichomonas vaginalis in vitro was compared to the efficacy of
metronidazole as a reference drug. Results showed that berberine sulphate was
comparable to metronidazole as regards potency with the advantage of being more
safe and possible replacement in metronidazole resistant cases.

Publication Types:
Evaluation Studies

PMID: 11775115 [PubMed /​ indexed for MEDLINE]

7: Folia Microbiol (Praha). 2001;46(2):137/​42.

Individual and combined effects of berberine and santonin on spore germination
of some fungi.

Singh B, Srivastava JS, Khosa RL, Singh UP.

Department of Mycology and Plant Pathology, Institute of Agricultural Sciences,
Banaras Hindu University, Varanasi/​221 005, India.

Berberine and santonin were isolated from rhizomes of Berberis aristata and
unexpanded flower buds of Artemisia maritima, respectively. Efficacy of these
two chemicals individually as well as of their mixtures, was tested against
spore germination of some saprophytic and obligate fungi. While berberine
individually was effective against most of the fungi, Helminthosporium spp. were
least affected even at the highest dose (1500 ppm). Santonin was equally
effective against several fungi. Mixture of both alkaloids found to be more
effective than individual ones. Keeping the dose of berberine constant and
santonin at two different concentrations (viz. 250 and 500 ppm) the spore
germination of Helminthosporium oryzae was stimulated. Increasing concentration
of santonin inhibited the spore germination of all other fungi tested,
Colletotrichum capsici being affected only by 20 and 5% (at berberine
concentration of 250 and 500 ppm, respectively). On the other hand, santonin
being constant and berberine at different concentrations, the mixture was
effective against all the fungi.

PMID: 11501401 [PubMed /​ indexed for MEDLINE]

8: Fitoterapia. 2000 Feb;71(1):25/​33.

Studies on preventive and curative effects of berberine on chemical/​induced
hepatotoxicity in rodents.

Janbaz KH, Gilani AH.

Department of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.

Berberis aristata is an edible plant employed in the South Asian Traditional
Medicine, particularly its fruits being used as a tonic remedy for liver and
heart. In this investigation, berberine, a known compound from this plant, was
studied for its possible antihepatotoxic action in rats. Pretreatment of animals
with berberine (4 mg/kg; orally twice daily for 2 days) prevented the
acetaminophen/​ or CCl4/​induced rise in serum levels of alkaline phosphatase
(ALP) and aminotransaminases (AST and ALT), suggestive of hepatoprotection.
Post/​treatment with three successive oral doses of berberine (4 mg/kg every 6 h)
reduced the hepatic damage induced by acetaminophen, while CCl4/​induced
hepatotoxicity was not modified, suggesting a selective curative effect against
acetaminophen. Pretreatment of animals with a single oral dose of berberine (4
mg/kg) induced prolongation of the pentobarbital (60 mg/kg, i.p.)/​induced
sleeping time as well as increased strychnine (0.3 mg/kg; i.p.)/​induced
toxicity, suggestive of inhibitory effect on microsomal drug metabolizing
enzymes, cytochrome P450s (CYPs).

PMID: 11449466 [PubMed /​ indexed for MEDLINE]

9: J Pharm Pharmacol. 2001 May;53(5):763/​8.

Inhibition of chemical carcinogenesis by berberine in rats and mice.

Anis KV, Rajeshkumar NV, Kuttan R.

Amala Cancer Research Centre, Kerala, India.

Berberine, an alkaloid isolated from the plant Berberis aristata, has been found
to inhibit significantly the carcinogenesis induced by 20/​methylcholanthrene
(200 microg/0.1 mL/mouse) or N/​nitrosodiethylamine (NDEA; 0.02% NDEA in
distilled water, 2.5 mL/animal by gavage, five days a week for 20 weeks) in a
dose/​dependent manner in small animals. Administration of berberine (0.5, 2.5 or
5.0 mg kg(/​1)) could reduce significantly the incidence of tumour in animals
after an injection of 20/​methylcholanthrene and increased their life span
compared with the control. When berberine (10, 25 or 50 mg kg(/​1)) was
administered simultaneously with NDEA, the markers of liver injury (liver
weight, gamma/​glutamyl transpeptidase activity and glutathione S/​transferase
level) were reduced significantly compared with animals treated with NDEA only,
which resulted in all the values being elevated. A similar decrease was noted in
the serum levels of lipid peroxide, bilirubin and glutamate pyruvate
transaminase. Morphology of liver tissue and levels of marker enzymes indicated
that berberine offered protection against chemical carcinogenesis.

PMID: 11370717 [PubMed /​ indexed for MEDLINE]

10: Altern Med Rev. 2000 Apr;5(2):175/​7.

Berberine.

[No authors listed]

Berberine is a plant alkaloid with a long history of medicinal use in both
Ayurvedic and Chinese medicine. It is present in Hydrastis canadensis
(goldenseal), Coptis chinensis (Coptis or goldenthread), Berberis aquifolium
(Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree
turmeric). The berberine alkaloid can be found in the roots, rhizomes, and stem
bark of the plants. Berberine extracts and decoctions have demonstrated
significant antimicrobial activity against a variety of organisms including
bacteria, viruses, fungi, protozoans, helminths, and chlamydia. Currently, the
predominant clinical uses of berberine include bacterial diarrhea, intestinal
parasite infections, and ocular trachoma infections.

PMID: 10767672 [PubMed /​ indexed for MEDLINE]

11: Gen Pharmacol. 1999 Nov;33(5):407/​14.

Possible mechanism of selective inotropic activity of the n/​butanolic fraction
from Berberis aristata fruit.

Gilani AH, Janbaz KH, Aziz N, Herzig MJ, Kazmi MM, Choudhary MI, Herzig JW.

Department of Physiology and Pharmacology, Faculty of Health Sciences, The Aga
Khan University, Karachi, Pakistan.

Berberis aristata is an edible plant employed in South Asian traditional
medicine; in particular, its fruit is used as a tonic remedy for liver and
heart. In isolated cardiac tissues, Berberis aristata fruit extract exhibits a
positive inotropic action. Activity/​directed fractionation using organic
solvents revealed that the cardiotonic activity is concentrated in the
n/​butanolic fraction (BF). The cardiac action of BF was investigated in
spontaneously beating right atria and in electrically driven right ventricular
strips and left atria obtained from reserpinized guinea pigs. The results show
that this fraction produces a dose/​dependent positive inotropic action with
little effect on heart rate. To study its possible mode of action, guinea pig
atria were pretreated with propranolol, a beta/​adrenoceptor blocking agent. This
treatment abolished the cardiotonic effect of isoprenaline, whereas the
cardiotonic effect of BF remained unaltered, suggesting that this effect does
not involve stimulation of beta/​adrenoceptors. On the other hand, application of
carbachol reverses only part of the BF/​induced increase in ventricular force of
contraction, indicating that besides a cyclic AMP (cAMP)/​dependent mechanism, a
cAMP/​independent mechanism underlies the inotropic action of BF. This is in line
with the observation that the dynamics of isometric twitch contractions are not
significantly altered by BF. Investigations in skinned myocardial preparations
showed that BF modulates the calcium/​dependent interaction of actin and myosin,
apparently by reducing the cooperativity of the calcium/​dependent binding of
myosin to actin, i.e., there is enhanced calcium activation at low to
physiological intracellular calcium, and reduced calcium activation at high
intracellular calcium concentrations as present, for example, in ischemic
calcium overload. These data indicate that the edible plant, Berberis aristata,
contains active principle(s) that cause(s) a selective inotropic effect,
involving/​in the form of the modulatory effect on actin myosin cooperativity/​a
novel mechanism of action. Further phytochemical and pharmacological studies may
lead to isolation and structural identification of an attractive, new
cardiotonic agent from Berberis aristata fruit.

PMID: 10553882 [PubMed /​ indexed for MEDLINE]

12: J Ethnopharmacol. 1996 Nov;54(2/​3):119/​24.

Activity of a crude extract formulation in experimental hepatic amoebiasis and
in immunomodulation studies.

Sohni YR, Bhatt RM.

Department of Biology, Alabama A&M University, Normal 35762, USA.

The activity of a crude extract formulation was evaluated in experimental
amoebic liver abscess in golden hamsters and in immunomodulation studies. The
formulation comprises the following five plants/​Boerhavia diffusa, Tinospora
cordifolia, Berberis aristata, Terminalia chebula and Zingiber officinale. The
formulation had a maximum cure rate of 73% at a dose of 800 mg/kg/day in hepatic
amoebiasis reducing the average degree of infection (ADI) to 1.3 as compared to
4.2 for sham/​treated controls. In immunomodulation studies humoral immunity was
enhanced as evidenced by the haemagglutination titre. The T/​cell counts remained
unaffected in the animals treated with the formulation but cell/​mediated immune
response was stimulated as observed in the leukocyte migration inhibition (LMI)
tests.

PMID: 8953425 [PubMed /​ indexed for MEDLINE]

13: J Ethnopharmacol. 1995 Jan;45(1):43/​52.

The antiamoebic effect of a crude drug formulation of herbal extracts against
Entamoeba histolytica in vitro and in vivo.

Sohni YR, Kaimal P, Bhatt RM.

Microbiology Department, CHM College, University of Bombay, India.

The antiamoebic effect of a crude drug formulation against Entamoeba histolytica
was studied. In the traditional system of medicine in India, the formulation has
been prescribed for intestinal disorders. It comprises of five medicinal herbs,
namely, Boerhavia diffusa, Berberis aristata, Tinospora cordifolia, Terminalia
chebula and Zingiber officinale. The dried and pulverized plants were extracted
in ethanol together and individually. In vitro amoebicidal activity was studied
to determine the minimal inhibitory concentration (MIC) values of all the
constituent extracts as well as the whole formulation. The formulation had a MIC
of 1000 micrograms/ml as compared with 10 micrograms/ml for metronidazole. In
experimental caecal amoebiasis in rats the formulation had a curative rate of
89% with the average degree of infection (ADI) reduced to 0.4 in a group dosed
with 500 mg/kg per day as compared with ADI of 3.8 for the sham/​treated control
group of rats. Metronidazole had a cure rate of 89% (ADI = 0.4) at a dose of 100
mg/kg per day and cured the infection completely (ADI = 0) when the dosage was
doubled to 200 mg/kg per day. There were varying degrees of inhibition of the
following enzyme activities of crude extracts of axenically cultured amoebae:
DNase, RNase, aldolase, alkaline phosphatase, acid phosphatase, alpha/​amylase
and protease.

Publication Types:
Comparative Study

PMID: 7739226 [PubMed /​ indexed for MEDLINE]

14: Biochem Soc Trans. 1992 Nov;20(4):347S.

Prevention of acetaminophen/​induced liver damage by Berberis aristata leaves.

Gilani AH, Janbaz KH.

Department of Pharmacology, Faculty of Health Sciences, Aga Khan University
Medical College, Karachi, Pakistan.

PMID: 1487011 [PubMed /​ indexed for MEDLINE]

15: Exp Parasitol. 1985 Dec;60(3):404/​13.

Leishmania donovani: amastigote inhibition and mode of action of berberine.

Ghosh AK, Bhattacharyya FK, Ghosh DK.

Berberine, an alkaloid from Berberis aristata Linnaeus, may be a useful drug for
the treatment of visceral leishmaniasis. In both the 8/​day and long/​term models
of Leishmania donovani infection in hamsters, it markedly diminished the
parasitic load and proved to be less toxic than pentamidine. It rapidly improved
the hematological picture of infected animals. Like pentamidine, it inhibited in
vitro multiplication of amastigotes in macrophage culture and their
transformation to promastigotes in cell free culture. Manometric studies showed
that both drugs had inhibitory action on both the endogenous and the
glucose/​stimulated respiration of amastigotes. They inhibited incorporation of
[14C]adenine, [14C]uracil, and [3H]thymidine into nucleic acids, and of
[14C]leucine into the protein of amastigotes, indicating an inhibitory action on
macromolecular biosynthesis. They also decreased deoxyglucose uptake. Using
spectrophotometric, spectrofluorimetric, and circular dichroism techniques,
berberine was found to interact in vitro with nuclear DNA from L. donovani
promastigotes.

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

PMID: 4076392 [PubMed /​ indexed for MEDLINE]

16: Infect Immun. 1982 Feb;35(2):471/​5.

Berberine inhibits intestinal secretory response of Vibrio cholerae and
Escherichia coli enterotoxins.

Sack RB, Froehlich JL.

Berberine, an alkaloid from the plant Berberis aristata, which has been known
since ancient times as an antidiarrheal medication in India and China, inhibited
by approximately 70% the secretory responses of the heat/​labile enterotoxins of
Vibrio cholerae and Escherichia coli in the rabbit ligated intestinal loop
model. The drug was effective when given either before or after enterotoxin
binding and when given either intraluminally or parenterally; it did not inhibit
the stimulation of adenylate cyclase by cholera enterotoxin and caused no
histological damage to intestinal mucosa. Berberine also markedly inhibited the
secretory response of E. coli heat/​stable enterotoxin in the infant mouse model.
Although the mechanism of action of the drug is not yet known, these data
provide a rationale for its apparent clinical usefulness in treating acute
diarrheal disease.

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

PMID: 7035365 [PubMed /​ indexed for MEDLINE]