berberis aristata: daru haridra: indian barberry - Hillgreen

BERBERIS ARISTATA: DARU HARIDRA: INDIAN BARBERRY
Berberis aristata (Berberidacease) a well-known liver tonic is widely distributed throughout India. It has
been traditionally used as a blood purifier. It is widely used in Chinese folk medicine as anti-arhythmics &
anti-hypertensive. Roots have been used in European folk medicine for inflammation.
DESCRIPTION
Stem- Berberis aristata available in pieces of variable length and thickness, bark about 0.4 – 0.8 cm thick,
pale yellowish-brown, soft closely and rather deeply furrowed, rough, brittle, xylem portion yellow, more
or less hard, radiate with xylem rays, pith mostly absent, when present small, yellowish-brown when
dried, fracture short in bark region, splintery in xylem; taste, bitter.
Powder-yellow; shows mostly fragments of cork ells, sieve elements, yellow coloured phloem fibres entire
or in pieces, stone cells in singles or in groups, numerous prismatic crystals of calcium oxalate, xylem
vessels having spiral thickening, thick-walled, lignified xylem fibres and ray cells.
TRADITIONAL MEDICINAL USES
Berberis aristata has played a prominent role in herbal healing for more than 2,500 years. The ancient
Egyptians used it to prevent plagues. India’s Ayurvedic healers used it foe dysentery. During the early
middle ages, European herbalists used it to treat liver and gallbladder ailments. Russian healers used it for
inflammations, high blood pressure, and for abnormal uterine bleeding. American Indians recognize
barberry as similar to Oregon grape.
Tincture made from Berberis aristata is used as a bitter tonic, stomachic, cholagogue, antiperiodic and
alterative, in cases of remittent as well as intermittent fevers and also in debility consequent therefrom
and is very effective in periodic neuralgia and menorrhagia. As an antiperiodic on frequently repeated
administration, it doses not produce is the case with cinchona and quinine and it may be used during the
attack of fever. Rasaut a preparation of Berberis aristata mixed with honey is useful in the treatment of
aphthous sores abrasions andulcerations of the skin. The plant is an emmenagogue and is useful in the
treatment of jaundice, enlargement of spleen, etc. the drug is also regarded as laxative, diaphoretic,
antipyretic and antiseptic.
Berberis aristata root bark decoction is externally used as a wash in painful eye affections, ulcers and
hemorrhoids. In the Unani system of medicine, it is used for the treatment of leprosy. Decoction of roots
of Berberis aristata is used for skin troubles and in blood purification.
CHEMICAL CONSTITUENTS
The chief constituent of the roots and stem bark of Berberis aristata is an alkaloid Berberine which is
reported to be responsible for hepatoprotective activity of Berberis aristata other constituents including
berbamine, aromoline, palmatine oxyacanthine and oxyberberine are also isolated. Alcoholic extract of
the bark of Berberis aristata yielded berberine, berberine chloride and palmatine chloride (yield of the
alkaloids as salts, is 4% of dry wt of bark).
Berberine

Berbamine
Palmatine
Oxyacanthine
PHARMACOLOGICAL ACTIVITIES AND CLINICAL TRIALS
Anti-carcinogenic activity
Berberin, 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 dosedependent
manner in small animals. Administration of berberine (0.5, 2.5 or 5.0 mg kg(-1) could reduce
significantly the incidence of tumor 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.
Anti-diarrheal activity
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
entertoxin 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.
Oral doses of berberine (>25 mg/kg) and Geranium extract showed significant inhibition of diarrhoea in
mice and both substances inhibited spontaneous peristalsis in rat intestine. Comparison to atropine and
papaverine indicated that the antidiarrhoeal activity of berberine differs form that of Geranium extract.

The effect of berberine on E. coli-induced intestinal fluid accumulation was observed in rats. Oral
administration of berberine (0.1 mg) together with the E. coli enterotoxin resulted in significant (P < 0.01)
reduction in fluid accumulation. Treatment with berberine prior to or after administration of the
enterotoxin was ineffective.
Intragastric administration of berberine sulphate reduced the purging effects of castor oil or Gassia
angustifolia leaf in mice. It did not affect the gastrointestinal transport of Chinese ink in normal mice.
The goal of drug therapy of diarrhoeal disease is to decrease stool water. This can be done in two ways:
increase the absorption of water and electrolytes or decrease the stimulated secretion. Berberine
probably does the later. Berberine does not significantly alter normal ileal water and electrolyte transport
as measured in vivo and in vitro. Two studies have been contradictory as to whether berberine alters
cholera toxin-induced stimulation of the adenylate cyclade-cAMP system. Hence the precise mechanism
of action of berberine is not known but its site of action appears to be distal to second messenger
production and may be at a level common to all stimuli of colonic chloride secretion.
Anti-fungal activity
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 satonin inhibited the spore
germination of all other fungi tested, collectotrichum 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.
Antihepatotoxic action
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 CC14-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 CC14-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 stychnine (0.3 mg/kg; i.p.)-induced toxicity, suggestive of inhibitory
effect on microsomal drug metabolizing enzymes, cytochromeP450s (CYPs).
Antihistaminic and anticholinergic activity
Berberry (Berberis vulgaris) is a well known medicinal plant in Iran and has also been used as food. The
antihistaminic and anticholinergic activity of aqueous extract of barberry fruits were investigated on
isolated guinea-pig ileum and dose response curves of histamine and acetylcholine with and without
extract were plotted. The pA2 values for antihistaminic activity of extract and dexchlorpheniramine were
calculated (extract; pA2 +/- S.E.M. = 4.50 +/- 0.01 [-log C (g/l)]; dexchlorpheniramine; pA2 +/- S.E.M. =
4.37 +/- 0.03[-log C (M)]) and compared with each other. The pa2values for anticholinergic activity of
extract and atropine were also calculated (extract, pA2 +/- S.E.M. = 8.99 +/- 0.13[-log C (M0] and
compared. The results indicated antihistaminic and anticholinergic activity of extract that seems to be of
the competitive type.

Anti-inflammatory activity
Extracts obtained from the roots and barks of various Berberis species are used as folk remedy worldwide
for the treatment of various inflammatory ailments including lumbago, rheumatism and to reduce fever.
Effects of the extracts and fractions from the roots of Berberis crataegina DC. (Berberidaceae) were
studied using various in vivo models of inflammation in mice and rats and observed potent inhibitory
activity against carrageenan-and serotonin-induced hind paw oedema, acetic acid-induced increased
vascular permeability, castor oil-induced diarrhoea and Freund’s complete adjuvant-induced (FCA)
arthritis models. Through bioassay-guided fractionation berberine was isolated as the main active
ingredient. Moreover, a dose-dependent analgesic activity was determined, which assessed by using the
model based on the inhibition of acetic acid-induced writhing reflexes as well as antipyretic activity on
FCA-induced increased body temperature. Acute and subchronic toxicity studies were also performed.
Extracts obtained from the roots of Berberidaceae species have been used in Eastern and Bulgarian folk
medicine in rheumatic and other chronic inflammatory disorders. The investigations of the chemical
composition and immunological properties show that their activity is mainly due to the alkaloid
constituents. In the present study the anti-inflammatory properties of total ethanol extract (TEE), three
alkaloid fractions, a major alkaloid berberine and oxyacanthine isolated from Berberis vulgaris roots were
compared. All these were applied in acute inflammation (carrageenan- and zymosan-induced paw
oedema), as the TEE showed the highest reducing effect. Their ability to alter in vivo and in vitro
complement activity was determined. Also, the TEE was most effective in a chronic inflammatory model
of adjuvant arthritis. The protoberberine fractions Bv2, Bv3 and berberine suppressed a delayed type and
berberine diminished antibody response against SRBC in vivo. The in vitro treatment of splenocytes with
berberine showed that the anti-SRBC antibody synthesis was influenced in a different manner depending
on the time course of its application. Oxyacanthine was less effective than berberine in the tests used.
Anti-microbial activity
The antimicrobial activity of Berberis heterophylla leaves, stems and root aqueous extracts was studied in
vitro on Gram-positive and Gram-negative bacteria and fungi. The in vitro antifungal activity of berberine
isolated from the same source against different Candida species was also investigated.
For the structure-activity relationship study on berberrubine derivatives, a series of compounds bearing 9-
O-acyl- and 9-O-alkyl-substityents were synthesized and tested for antimicrobial activity against Grampositive,
Gram-negative bacteria and fungi. Octanoyl, decanoyl, lauroxyl derivatives among the acyl
analogs and hexyl, heptyl, octyl, nonyl, decyl, undecyl derivatives among the alkyl analogs Gram-positive
bacteria and fungi. As a whole alkyl analogs were more active than acyl analogs for antimicrobial activity
on Gram-negative bacteria. Too short or too long substituents decreased activity. These results suggest
that the presence of lipophilic substituents with moderate sizes might be crucial for the optimal
antimicrobial activity.
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 chinesis (coptis or goldenthread), 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 helminths and chlamydia. Currently, the
perdominant clinical uses of berberine include bacterial diarrhea, intestinal parasite infections and ocular
trachoma infections.
Multidrug resistance pumps (MDRs) protect microbial cells from both synthetic and natural
antimicrobials. Amphipathic cations are preferred substrates of MDRs. Berberine alkaloids, which are
cationic antimicrobials produced by a variety of plants are readily extruded by MDRs. Several Berberis
medicinal plants producing berberine were found also to synthesize an inhibitor of the NorA MDR pump
of a human pathogen Staphylococcus aureus. The inhibitor was identified as 5’-methoxyhydnocarpin (5’-

MHC), previously reported as a minor component of chaulmoogra oil, a traditional therapy for leprosy. 5’-
MHC is an amphipathic weak acid and is distinctly different from the cationic substratesof NorA. 5’-MHC
had no antimicrobial activity alone but strongly potentiated the action of berberine and other NorA
substrates against S. aureus. MDR-dependent efflux of ethidium bromide and berberine from S. aureus
cells was completely inhibited by 5’-MHC. The level of accumulation of berberine in the cells was
increased strongly in the presence of 5’-MHC, indicating that this plant compound effectively disabled the
bacterial resistance mechanism against the berberine antimicrobial.
Antipyretic activity
Significant oral antipyretic activity in rabbits was exhibited by hexane-, chloroform- and water-soluble
extracts of Artemidia absinthium, Viola odorata, Melia azadirachta and Fumaria parviflora comparable in
potency aspirin. Pyresis was induced by subcutaneous yeast injections. Antipyretic activity was more
prominent in the hexane-soluble portions of these plants. Insignificant to no antipyretic effects were
produced by extracts of Butea frondosa, berberis lycium and Sisymbrium irio. No obvious toxic effects
were noted for any of the plant extracts up to doses of 1.6 g/kg.
Anti-tumor activity
The enzyme cyclooxygenase-2 (COX-2) is abundantly expressed in colon cancer cells and plays a key role
in colon tumorigenesis. Compounds inhibiting COX-2 transcriptional activity have therefore potentially a
chemopreventive property against colon tumor formation. An assay method for estimating Cox-2
transcriptional activity in human colon cancer cells was established using a beta-galactosidase reporter
gene system and examination was made of various medicinal herbs and their ingredients for an inhibitory
effect on COX-2 trascriptional activity. We found that berberine, an isoquinoline alkaloid present in plants
of the genera Berberis and Coptis, effectively inhibits COX-2 transcriptional activity in colon cancer cells in
a dose- and time-dependent manner at concentrations higher than 0.3 microM. The present findings may
further explain the mechanism of anti-inflammatory and anti-tumor promoting effects of berberine.
Activator protein 1 (AP-1) is a transcription factor which plays a critical role in inflammation and
carcinogenesis. The present study was conducted to investigate the effect of berberine, an isoquinoline
alkaloid present in plants of the genera Berberis and Coptis on the activity of AP-1 using a reporter gene
assay in human hepatoma cells. Berberine was shown to inhibit AP-1 activity in a dose- and timedependent
manner at concentrations higher than 0.3 microM. Berberine inhibited AP-1 activity almost
completely as low as 10 microM after 48 h treatment. The inhibitory effect on AP-1 activity in cancer cells
may further explain the anti-tumor promoting activity of berberine.
Cardiovascular activity
An in vitro study indicated that berberine inhibits voltage-dependent and ATP-sensitive potassium
channels. The hypoglycaemic and antiarrhythmic activity of berberine might be due to its potassium
channel-blocking effects. Intravenous administration of berberine (1 mg/kg) decreased the amplitude of
delayed after-depolarizations and blocked arrhythmias in rabbit ventricular muscles. The mechanism of
antiarrhythmic activity of berberine may therefore be due to suppression of delayed after-depolarizations
caused by a decrease in sodium influx.
Administration berberine sulphate increased the number of thrombocytes, decreased the activity of
factor XIII and promoted blood coagulation in intact and gamma-irradiated rats and mice.
Berberine inhibited platelet aggregation and platelet adhesiveness in rats with reversible middle cerebral
artery occlusion. Thromboxane B2 levels after treatment with berberine were lower than levels in
untreated ischaemic controls. The decline of platelet aggregation and decrease of thromboxane B20 may
be one of the important factors behind the antiischaemic activity of berberine.
Berberine markedly inhibited clot retraction in vitro, which may be due to direct inhibition of calcium ion
influx.

Cytotoxic activity
Berberine demonstrated cytotoxic activity in a particular yeast strain in vitro, blocking mutation in the
DNA strand-break repair pathway, and caused growth inhibition in vitro in human hepatoma cells,
increasing glucocorticoid receptor levels compared to control cells.
Berberine activated macrophages to be highly cytostatic against tumour cells and caused morphological
changes to human leukaemia cells was characteristic of apoptosis the programmed death function of the
cell.
Protoberberines have been identified as poisons of topoisomerases 1 and 11 (enzymes involved in DNA
replication and transcription) which supports their in vitro antitumour activity.
Diabetes mellitus
An uncontrolled clinical trial investigated the effect of berberine on 60 patients with type 11 diabetes
mellitus. The patients varied in severity of this disorder. Oral doses (0.3-0.5 g three times a day) were
prescribed for 1-3 months, together with a therapeutic diet prescribed for 1 month. Major symptoms of
diabetes disappeared patients strength improved, blood pressure became normal and blood lipids
decreased. Fasting glycaemic levels in 60% of patients ere controlled. Further testing in animal models
indicated that treatment with berberine led to healthier pancreatic tissue compared to controls. It is
suggested that the mechanism of action of berberine may be associated with promoting regeneration and
functional recovery of β-cells.
Effects on smooth muscle
Berberine causes a slow diminution of tone, amplitude, rate and response to acetylcholine in rat uterus.
Hydrastine increased the rate of uterine contraction, with slowly decreasing tone and amplitude.
Berberine and hydrastine together produced a rapid decrease in tone and amplitude, similar to that
produced by Hydrastis extract. The author suggested that, although commonly regarded as a uterine
stimulant, Hydrastis was in fact a uterine sedative. Hydrastis extract and total crude alkaloids of Hydrastis
demonstrated antispasmodic action on isolated mouse intestine and uterus.
In contrast, an alcohol extract of Hydrastis produced a vasoconstrictive effect but inhibited contraction of
rabbit arota induced by adrenaline, serotonin and histamine in vitro. However, berberine and hydrastine
did not show this vasoconstractive effect. Berberine demonstrated some inhibiting activity on aortic
contraction induced by adrenaline by hydrastine was inactive. The observe vasoconstrictive effect of
Hydrastis extract may be due to the presence of hydrastis, a decomposition product of hydrastin.
The four major alkaloids of Hydastis (berberine, hydrastine, canadine and canadaline) were tested on
rabbit aorta strips for adrenolytic activity (inhibition of adrenaline-induced contraction). The total extract
had a lower adrenolytic potency than the alkaloid mixture and the authors suggested that berberine,
canadine and canadaline act synergistically and the presence of other compounds (in particular hydrastin)
probably counteracts their activity.
The major alkaloids of Hydrastis (berberine, hydrastine, canadine and canadaline) evoked contractile
activity on isolated guinea pig ileum through an indirect cholinergic mechanism, acting on acetylcholine
release from nerve endings. They demonstrated differing contractile potencies depending on chemical
structure.
In confirmation of earlier research, an ethanolic extract of Hydrastis exhibited reversible relaxant a
activity on spontaneous contractions in non-pregnant rat uterus and also on contractions induced by
serotonin, oxytocin and acetylcholine. The extract also relaxed carbachol precontracted guinea pig
trachea. An ethanolic extract of Hydrastis induced strong relaxation in rabbit bladder detrusor muscle but
the four major individual alkaloids were inactive.

Gastrointestinal effects
Small intestine transit time in 20 healthy human subjects was significantly delayed after oral
administration of 1.2 g of berberine (P > 0.01). Therefore the antidiarrhoeal property of berberine might
be additionally mediated by its ability to delay small intestinal transit.
A clinical trail compared the effect of an antiulcer drug (rantidine) and four antibacterial drugs, one of
which was berberine (300 mg twice daily), on patients with H. pylori-associated duodenal ulcer disease.
Although the antibacterial drugs were more effective in H. pylori clearance and improvement of gastritis,
ranitidine proved more effective in ulcer healing (Acid secretion may therefore be of more importance in
ulcer formation than H. pylori).
Giardiasis
Berberine was administered at a dose of 5 mg/kg/day for 6 days to 25 giardiasis patients between the
ages of 1 to 10 years; 68% became negative for the presence of Giardia cysts. In a similar group receiving
placebo, only 25% experienced a parasitological cure. Flagyl (metronidazole) at a dosage of 10 mg/kg/day
for 6 days was 100% effective in another nine patients.
A clinical trial conducted on children (5 months to 14 years) with giardiasis compared the effect of
berberine with established antigiardial drugs. A group of 42 patients received 10 mg/kg/day of berberine
orally for 10 days; 90% of patients had negative stool specimens upon completion of treatment, although
a small number of cases relapsed 1 month later. This result compared favourably with the other three
antigiardial drugs investigated.
Immunomodulation activity
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 plant-
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 amoeblasis 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 evidence 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.
Influence on T-cell mediated immunity
The protoberberine alkaloid berberin is isolated as a main alkaloid from the roots and bark of Berberis
vulgaris. Berberine strongly inhibited in vitro the proliferative response of mouse spleen cells to Tdependent
mitogens concanavalin A (con A) and phytochemagglutinin (PHA). Spleen cells obtained from
berberine-treated mice (10 mg/kg/3) days) expressed enhanced proliferative response to both mitogens.
Berberine was applied to mice at different intervals before or after the induction of adjuvant arhritis (AIA)
and Candida albicans (C. albicans) infection. The application of the alkaloid to new born mice (5 days after
birth at a dose of 5 mg/kg/3 days) did not change the course of AIA and C. albicans infection. Its
application at three 10 day intervals (5 mg/kg), starting from the 5 day after birth increased the joint
inflammation in AIA. The host resistance to C. albicans infection was not affected, while the delayed type
hypersensitivity (DTH)-reaction against the pathogen was enhanced. The alkaloid inhibited the
development of AIA when applied after its onset (10 mg/kg from day +3 to +12 day). Berberine treatment
during the ongoing infection did not influence its outcome (from +2 to +10 day).
Berbamine, an ingredient of Berberis, which itself is widely utilized in Chinese folk medicine has been used
as a source of leukogenics, anti-arrhythmics and anti-hypertensives. In recent years the
immunosuppressive effects of berbamine has been demonstrated. In order to further investigate the
value of berbamine as an immunosuppressive agent, the delayed type hypersensitivity reaction (DTH)

esponse with sheep red blood cells (SRBC), the mixed lymphocyte reaction (MLR) and a skin model of
allograft rejection on mice were studied. Berbamine showed suppressive effects on DTH and MLR and
significantly prolonged allograft survival compared with untreated transplanted mice. The results indicate
that berbamine may be a potential agent in clinical transplantation.
Intropic activity
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 intropic 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 dosedependent
positive inotropic action with little effect of 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 low to
physiological 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 inotrpic 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.
Liver cirrhosis
Patients with cirrosis of liver have high plasma concentrations of tyramine, which can causes
cardiovascular and neurologic complications. An uncontrolled clinical trial investigated the effect of oral
berberine on hypertyraminaemia in cirrhotic patients over several months. Oral administration of
berberine (600-800 mg/day) corrected hypertyraminaemia and prevented the chemical tyramine levels
following chemical tyramine stimulation. This effect was probably due to inhibition of bacterial tyrosine
decarboxylase in the intestine.
Pharmacokinetics
Oral administration of 50 mg/100 g to rabbits resulted in a maximum level of berberine in the blood after
8 hours. Berberine was still found in the blood after 72 hours. Levels were highest in the heart pancreas
and liver and it was excreted through the stools and the urine.
A study investigated the concentration of berberine in rat plasma after oral administration of aqueous
extracts of Coptis spp. coadministration with aqueous extract of Glycyrrhiza did not influence the
bioavailability of berberine from the Coptis extract.
Toxicology
The oral LD in mice of berberine is 329 mg/kg. Oral doses of up to 100 mg/kg of berberin sulphate have
been well tolerated in animal studies without lasting effects. However, prolonged administration caused
organ damage and death after 8-10 days.
The oral LD of Hydrastis canadensis extract in mice is 1620 mg/kg.

The LD of berberine sulphate in mice by intraperitoneal route is 24.3 mg/kg. In high doses, berberine
caused haemorrhagic nephritis and eventually death by respiratory failure.
Trachoma
Fifty-one patients with clinically active trachoma lesions (stages 1 and 11) were treated for 8 weeks with
eyedrops of either 0.2% berberine chloride or the antitrachoma drug, sulfacetamide eyedrops gave the
best clinical results but the infective agent (Chlamydia trachomatis) remained present in the conjunctiva
and relapses of symptoms occurred. Berberine-treated patients showed only very mild ocular symptoms
and were negative for infective agent. Also, no relapses occurred among these patients.
A double-blind placebo-controlled clinical trial was conducted on 96 children with trachoma stage 11a or
11b over a period of 3 months. Berberine eyedrops (0.2%) were compared with berberine plus neomycin,
sulfacetamide and a placebo. In patients treated with berberine alone, 84% were clinically cured (p <
0.001) but only 50% were microbiologically cured. The response rate was higher in those treated with
berberine and neomycin and lower in the sulfacetamide group. Berberine treatment was better tolerated
than dulfacetamide.
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