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Barberry (Berberis sp)


Berberis aristata Image
Synonyms / Common Names / Related Terms
Agrecejo, almindelig berberis (Danish), alvo (Spanish), berbamine, Berberidaceae (family), berberidis cortex, Berberis aristata, Berberis dumetorum, berberidis radicis cortex, Berberis thunbergii, berberine bisulfate, berberitze, berberrubine, berberry, bervulcine, columbamine, crespino (Italian), curcuma, epine-vinette (French), European barberry, isotetrandine, jatorrhizine, jaundice berry, Lebanon barberry, mountain grape, oxyacanthine, palmatine, pipperidge bush, piprage, red barberry, sauerdorn (German), sowberry, uva-espin (Portuguese), vinettier, vulcracine.
Note: For further information regarding barberry's constituent berberine, please see the berberine monograph.



Mechanism of Action
Pharmacology:
  • Constituents: Medicinally used parts of barberry include the stem bark and root bark, although the berries have also been traditionally used. The chief constituent of barberry bark is berberine, a yellow crystalline, bitter alkaloid, one of the few that occurs in plants belonging to several different natural orders. Other constituents of Berberis are oxyacanthine, berbamine, berberrubine, bervulcine, columbamine, isotetrandine, jatorrhizine, oxycanthine, palmatine, vulcracine37,38, carbohydrates, organic acids, some vitamins, poliphenolic compounds, pectin, tannin, and mineral elements.39
  • According to one study, there is 6.1% of berberine in the root bark of Berberis vulgaris, and 0.4% in the woody portions of the root.40 The berries contain citric (vitamin C) and malic acids, and possess astringent and anti-scorbutic properties.
  • Adrenergic activity: Berberine has been found to competitively inhibit the binding of yohimbine in a fashion similar to that of clonidine, suggesting berberine has partial agonist activity at platelet alpha-2 receptors.33
  • Anti-amoebic activity: In an animal in vivo study, berberine has been shown to be effective at treating amoebiasis in a dose dependent manner in both mice and hamsters.41 The greatest effect was seen at doses of 100mg/kg in mice and 150mg/kg in hamsters.
  • Berberine, in doses of 2mg/kg intramuscularly or 3mg/kg given orally, was shown to prevent the development of hepatic amoebiasis in hamsters when given in three doses (every four hours).42
  • Antihypertensive activity: Berberine sulfate solution (5mg/mL) produced a dose-dependent decrease in blood pressure in anesthetized dogs, cats, frogs, and rats that was not inhibited by intravenous atropine, mepyramine maleate, pentolinium tartrate, propranolol or phenoxybenzamine.23 An in vitro study found that intravenous berberine caused a hypotensive effect in rats at a dose of 4mg/kg (p<0.01 for systolic; p<0.001 for diastolic); bradycardia occurred at 6mg/kg (p<0.01).22
  • The aqueous extract from Berberis vulgaris fruit (B.V.) was tested in male Sprague-Dawley rats (200-250g) to evaluate its antihypertensive effects on DOCA-induced hypertension.31 After five weeks, the rats were anaesthetized with thiopental (30mg/kg, intraperitoneal) and the arterial blood pressure was measured. The mean arterial blood pressure and heart rate were 231 +/- 6.4 (mmHg) and 506 +/- 12 (beats/min), respectively. Administration of B.V. extracts significantly reduced the rat arterial blood pressure. In in vitro studies, rings of descending aorta were cut and mounted for isometric tension recording in an organ chamber containing Krebs solution. Mesenteric beds were also removed and perfused with Krebs solution. After one hour of stabilization, preparations (aortic rings or mesenteric beds) were precontracted with phenylephrine (10(-5) M), then different concentrations of B.V. (0.4, 2 and 4mg/mL) were added which caused a relaxation in these vessels. To investigate the mechanism of action of the extract, the tissues were incubated with either L-NAME (10(-5) M) or indomethacin (10(-5) M) for 20 min. In the aortic rings L-NAME pretreatment could only reduce the vasodilatory effects of a low concentration of B.V. (0.4mg/mL), but indomethacin was without effect. In isolated perfused mesenteric beds preincubation with either L-NAME or indomethacin did not modify the vasodilator effects of the aqueous extract from B.V. fruit. The present results suggest that the antihypertensive and vasodilatory effects of B.V. fruit extract are mainly endothelial-independent and it may be used to treat hypertension, a status with endothelial dysfunction.
  • In another animal study, the effects of crude aqueous extract of barberry on rat arterial blood pressure and the contractile responses of isolated rat aortic rings and mesenteric bed to phenylephrine were investigated.30 Administration of the extract (0.05-1mg/100g body weight of rat) significantly reduced the mean arterial blood pressure and heart rate in anaesthetized normotensive and desoxycorticosteron acetate-induced hypertensive rats in a dose-dependent manner. Concentration-response curves for phenylephrine effects on isolated rat aortic rings and the isolated mesenteric beds in the presence of the extract were significantly shifted to the right. Application of the extract (1-50mcg/mL) shifted the activation threshold voltage to more negative potentials, leading to an enhancement in magnitude of the outward potassium current recorded from cells present in rat brain slices of parabrachial nucleus and cerebellum. This effect on potassium current may explain the sedative and neuroprotective effects of barberry. The present data support the hypothesis that the aqueous extract of barberry has beneficial effects on both cardiovascular and neural system suggesting a potential use for treatment of hypertension, tachycardia and some neuronal disorders, such as epilepsy and convulsion.
  • Anti-inflammatory activity: Berberine sulfate administered subcutaneously to the ears of mice in doses of 4 and 8mg/kg significantly inhibited xylene-induced swelling.10
  • The addition of berberine significantly inhibited the transformation of lymphocytes despite the presence of known mitogens in vitro, as measured by [3H] thymidine uptake by lymphocytes.3
  • Berberine has also been shown to inhibit activator protein-1 activity, which is essential for inflammation in an in vitro study.4
  • Berberine has been shown to inhibit the transcriptional activity of cyclo-oxygenase 2 (COX-2) enzyme in in vitro studies.4 COX-2 is induced by cytokines to engage in inflammation.
  • Berberine was shown to have statistically significant inhibition of interleukin 1 (IL-1) at doses of 10 and 20μg/mL.8
  • In an in vitro study, berberine was studied for its effects on the inhibition of interleukin-8 (IL-8).5 IL-8 is a cytokine that is actively involved in inflammatory processes. Berberine was shown to decrease IL-8 production by 40% when compared to control. However, a study conducted by Kostalova et al. showed that while a crude extract of berberine can decrease IL-8 production, the polysaccharide isolated from the crude extract can be a potent inducer of IL-8.36
  • Berberine was shown to significantly decrease leukotriene formation via an in vitro study. Monocyte production was decreased by 14%. In addition, PGE2 generation by monocytes was significantly inhibited by berberine by 78%.9
  • Berberine inhibited edema and inflammation induced in the guinea pig paw by carrageenan or zymosan solution.6
  • Antimicrobial activity (bacterial, fungal): Berberis heterophylla leaves, stems and root aqueous extracts, has purported antimicrobial activity in vitro on Gram-positive and Gram-negative bacteria and fungi.11 Berberine, at concentrations of 10mg/mL, exhibited antifungal activity versus Alternaria, Candida albicans, Curvularia, Drchslera, Fusarium, Mucor and Rhizopus oryzae; and concentrations of 25mg/mL were able to inhibit the growth of Aspergillus flavus and Aspergillus fumigates in vitro.1 Berberine was shown to have weak to moderate activity against Malassezia species.2
  • Berberine (0.5mg) injected into chick embryos, reduced the mortality rate of the embryos due to the injection of trachoma organisms into the yolk sac.43 Berberine demonstrated activity against Streptococcus pneumoniae in an in vivo study with white mice.44 The mice were given 6mg intraperitoneally every six trachoma hours for 24 hours. Only 57% of the infected mice were protected against infection in comparison to 100% in the arm that received ampicillin. Furthermore, a methanol extract of berberine has demonstrated cidal activity against T. vaginalis, G. lamblia, and E. histolytica in vitro.45
  • Berberine sulfate was shown to possess antimicrobial activity versus Gram-positive, Gram-negative, fungal and protozoan organisms in vitro, through the inhibition of RNA and protein synthesis.46 It has also been found to be bactericidal versus Vibrio cholera at concentrations of 35mcg/mL and versus Staphylococcus aureus at a concentration of 50mcg/mL.46
  • An in vitro study conducted by Chung et al. showed berberine to be effective in suppressing the growth of Helicobacter pylori in a dose dependent manner.20
  • Antineoplastic activity: In vitro study showed berberine to induce differentiation of human teratocarcinoma cells into cells with neuronal cell morphology, beginning one day after the addition of 0.1mg/mL berberine to the culture medium.47
  • An in vitro study evaluating the ability of 9-substituent protoberberine compounds to inhibit DNA topoisomerase I and II, found that 9-ethoxycarbonyl berberine significantly inhibits topoisomerase II.48
  • Proberberine exhibited similar actions to that of topoisomerase I and II poisons (sic), from three up to more than 10 times cytotoxic against solid cell tumors.49 The most potent against SF-268 cells was DM-II-24.
  • Berberine was shown in vitro to inhibit the DNA fragmentation and apoptosis of thymocytes induced by etoposide and camptothecin.50 Berberine has also been shown to inhibit activator protein-1 activity, which is essential for carcinogenesis in an in-vitro study.4 It can inhibit the transcriptional activity of cyclo-oxygenase 2 (COX-2) enzyme in in vitro studies.4 Studies have shown that the expression of COX-2 plays a role in colon tumorigenesis. Therefore, berberine may be tumor protective in colon cancer.
  • Another in vivo mice study showed that berberrubin, an isolate of barberry, is effective against sarcoma-180 ascities and that it has strong antitumor effects.51
  • After three days of continuous exposure in vitro, berberine significantly inhibited hepatoma cell growth in a dose-dependent manner, and also inhibited the release of alpha-fetoprotein after 18 hours of exposure.52
  • Berberine, in concentrations of 25(/mL, induced apoptosis during the S-phase of the cell cycle in promyelocytic leukemia HL-60 cells in vitro.53
  • Berberine has been shown to inhibit the in vitro synthesis of DNA, RNA, protein and lipids in ascitic tumor cell lines; however, this inhibition did not carry over to experiments performed in mice; and, when glucose was added to the in vitro cultures, inhibition was prevented.54
  • In a murine model of Lewis lung carcinoma, the oral administration of berberine, the active ingredient in barberry, for two weeks significantly inhibited mediastinal lymph node metastasis; however, there was no inhibition of tumor growth in the lung parenchyma.55
  • In vitro, berberine activated macrophages to inhibit the growth of tumor cells at concentrations above 0.15mcg/mL.56 Additionally, at concentrations above 1.5(/mL, berberine successfully inhibited DNA synthesis in the tumor cells.
  • In an experiment on mouse skin, berberine inhibited the action of tumor promoters, teleocidin and 12-O-tetradecanoylphorbol-13-acetate.57
  • In vitro, the addition of berberine to culture of six human brain tumor cell lines resulted in a mean 91% cell kill.27 In the rat model of gliosarcoma, berberine administration resulted in a mean 80.9% cell kill.27
  • Intravenous berberine, administered at a concentration of 0.2mg/kg/min, significantly raised left ventricular end-diastolic pressure in anesthetized dogs with embolized left main coronary arteries, simulating left ventricular heart failure.17
  • An in vitro study investigated the antimutagenic properties of berberine.58 In a Euglena gracilis assay, where the cells were mutated by acridine orange, 0.03mcg/mL of berberine was shown to significantly decrease the number of mutant cells, however there are no statistics to accompany the claim.
  • Li et al. have found that protoberberines, organic cations, are able to intercalate DNA and inhibit the enzyme topisomerase I with differing affinities dependent upon their substituent structures.59
  • Liu et al. conducted an animal study observing the effects of cyclophosphamide 2.5mg/kg for three days, berbamine 20mg/kg once daily for seven days, combination of cyclophosphamide and berbamine, and placebo on a Walker tumor.60 When compared to the control group on day eight, cyclophosphamide monotherapy had significantly decreased the activity of the tumor by 39.6% (p<0.05), berbamine monotherapy had decreased the activity by 44.9% (p<0.05), and the combination of the two decreased the activity by 61.8% (p<0.01).
  • Anti-oxidant activity: Berberine was shown to have antioxidant effects similar to that of vitamin E in the riboflavin system.12 Its effects are greater than vitamin E in the xanthine oxidase system.
  • In a comparative study, protoberberine, a constituent of barberry, was shown to inhibit lipoxygenase and lipid perioxidation leading to its antioxidant properties.61,13 It shown to have more activity in oxyberberine, corytuberine, and columbamine than in berberine.
  • Anti-parasitic activity: In vitro study has demonstrated the ability of berberine to completely inhibit the growth of promastigotes at a concentration of 5(/mL, while inhibiting endogenous respiration of the organism and inhibiting nucleic acid and protein synthesis.62 Subsequent study has shown berberine chloride to interact with Leishmania donovani nuclear DNA, inhibiting the multiplication of amastigotes in macrophage culture in vitro and to decrease the parasite load in animals.63
  • Anti-platelet activity: In vitro study has found that berberine inhibits platelet-activating factor aggregation of platelets with 50% inhibition at a concentration of 38(/mL; and, berberine inhibits the binding of platelet-activating factor to rabbit platelets with 50% inhibition seen at a concentration of 480(/mL64.
  • Animal study has shown berberine to inhibit platelet aggregation caused by ADP, arachidonic acid and collagen, as well as decrease the amount of thromboxane-B2 in rats with ischemic cerebral artery occlusion at doses of 20mg/kg for 1, 3, or 5 days.65
  • Anti-complementary activity was found to be due to the alkaloid fraction especially bisbenzylisoquinoline, a derivative of barberry.7
  • Xuan et al. conducted an animal study that showed that tetrahydroberberine, related to barberry, inhibited platelet aggregation in vivo and in vitro, which lead to the prevention of venous thrombosis.66
  • Antiproliferative activity: Some of the main constituents on barberry (berberine, berbamine, and oxyacanthine) have been shown to be effective in suppressing the proliferative activity of keratinocyes.16 In an in vitro study, berberine was shown with statistical significance to slow proliferation (p<0.05). In addition, the other two constituents tested, berbamine and oxyacanthine, was shown to be three times more effective than berberine (p<0.05).
  • Anti-secretory activity: Berberine sulfate administered orally in doses of 60mg/kg, significantly decreased the vascular permeability caused by 0.7% acetic acid in mice.10 Subcutaneous administration of berberine sulfate in doses of 20 and 50mg/kg inhibited vascular permeability induced by histamine.10
  • In rat ileum, berberine was shown to increase the absorption of Cl and bicarbonate. It also decreased the short circuit current. When berberine was administered to cholera toxin treated tissue, Na and Cl absorption was stimulated and adenylate cyclase was inhibited.67
  • Berberine has been shown to inhibit mast cell activation as well as mast cell dependent Cl secretion in in vitro studies involving rat colon.68
  • Berberine, significantly reduced the secretory response of pig jejunal segments induced by perfusion with a solution containing E. coli heat-stable enterotoxin.69 Also shown to inhibit the secretory response of E. coli. In rabbits and infant mice.70
  • Berberine significantly reduced the net secretion of water and electrolytes induced by E. coli heat stable enterotoxin in pig jejunum.28 In normal jejunal segments, berberine administration reversed the secretion of water and electrolytes induced by neostigmine.28
  • Berberine, an active ingredient in barberry, has been shown to inhibit the secretory response to E. coli heat-stable toxin in the intestines of Wistar rats when both berberine and toxin were administered together.71
  • Berberine was shown to have antisecretory effects on V. cholerae in rabbits even after the enterotoxin has already settled in the host.70
  • Cardiovascular activity: Berberine extract showed inhibitory activity on adrenaline-induced aortic contraction.72
  • A study in dogs to show the effects of berberine on Left Ventricular dP/dT (LV dP/dT) and Left Ventricular End Diastolic Pressure (LVEDP) in a failing heart.17 LV dP/dT is a measure of the contractile ability of the heart and it is a good measure of the initial velocity of the myocardial contraction. LVEDP is a measurement of the left ventricle's ability to receive blood from the left atrium thereby a measure of compliance. Berberine was shown to significantly increase LV dP/dT, LVEDP, and decrease total peripheral resistance (p<0.01). Cardiac output was also increase significantly (p<0.05) and ejection fraction was increased significantly (p<0.001).
  • Wang depicted the anti-arrhythmic properties of berberine in an in vitro and in an in vivo study.73 It was shown that even at 3mcM of berberine, amplitude of delayed after depolarization was decreased and triggered activity in ventricular papillary muscle was abolished. At 30mcM of berberine, delayed after depolarization either was decreased or no longer existed.
  • In vitro, berberine caused bradycardia in isolated right and left atria excised from guinea pigs, which was not prevented by atropine.74 Berberine also has exhibited positive inotropic effects, preventing and abolishing ouabain-induced ventricular arrhythmias75,76,77 in experiments in anesthetized dogs76 ,77. In guinea pigs, berberine had positive inotropic and negative chronotropic effects.74 Additional experiments in animals with induced ventricular arrhythmias and atrial fibrillation have also demonstrated the ability of berberine to restore normal sinus rhythm.15
  • Berberine also showed to have a concentration-dependent time to peak tension and cardiac relaxation time. Huang conducted an animal study showing the benefits of berberine on the ability to suppress ventricular premature beats (p<0.001) and ventricular tachycardia.14 ,78 Zalewski, et al. have found through animal study that berberine, in doses of 0.2mg/kg/min and 0.7mg/kg/min, increased cardiac output, and decreased total peripheral resistance and heart rate; while doses of 0.02mg/kg/min only increased cardiac output.79
  • Tetrahydroberberine, similar to berberine, was shown to reduce the infarct size of the left anterior descending artery four hours after ligation.80 The results of this study suggest that tetrahydroberberine can protect the myocardium from ischemic and reperfusion injury.
  • Berberine sulfate bolus injection (1mg/kg), administered to rats one minute after undergoing coronary artery occlusion, significantly reduced early mortality from ventricular fibrillation or complete arterioventricular block (36% mortality as compared to 66% mortality in the control group).81
  • Cholinergic activity: The administration of berberine (0.1 and 0.5g/kg) for 14 days was effective in improving scopolamine-induced amnesia in rats, an effect that was augmented by physostigmine and neostigmine.82 Results suggest that the anti-amnesic effect of berberine administration may be related to the increase in the peripheral and central cholinergic neuronal system activity.
  • Diuretic activity: Barberry contains vitamin C and may have a mild diuretic activity due to the acid content.
  • Gastrointestinal activity: Berberine given orally at doses of 0.06 to 20mg/kg daily significantly prolonged the latent period and decreased the frequency of purging (p<0.05).83 Also, in intact mice that received 10mg/kg daily, it delayed intestinal motility (p=0.01).
  • Oral berberine sulfate (40 and 80mg/kg) significantly decreased the occurrence of diarrhea induced by the ingestion of castor oil and Cassia angustifolia in mice.10
  • Sack et al. found through animal experiments with rabbit ligated intestinal loops, that berberine sulfate significantly inhibited the actions of V. cholera crude enterotoxin and E. coli heat-labile enterotoxin when administered before or up to 4 hours after toxin injection.70 In addition, berberine sulfate, at concentrations of 0.05 and 0.1mg, significantly inhibited the secretory response of infant mice to E. coli heat stable enterotoxin.
  • Swabb et al. found that berberine reduced the secretion of water, sodium, chloride and bicarbonate induced by cholera-toxin in rat ilea and prevented the edema seen in non-berberine treated controls.84
  • In twenty healthy subjects, the oral administration of 1.2g berberine significantly delayed small intestinal transit time of a meglucamine diatrizoate and sorbitol test mixture (71.10 ± 22.04min, control vs. 98.25 ± 29.03min, berberine, p<0.01).25 Results suggest that the antidiarrheal property of berberine might be mediated, at least in part, by its ability to delay the small intestinal transit.
  • Hepatic activity: Berberine has been shown to increase the secretion of bilirubin in rats with hyperbilirubinemia acutely, but the effect diminished with continued berberine exposure.85 A more recent study has shown berberine to displace bilirubin from albumin in both in vitro and animal studies, resulting in an increase in serum total- and direct-bilirubin concentrations.26 In an in vitro study, berberine was shown to be hepatoprotective when administered twice daily for two days before receiving toxic doses of acetaminophen.21 
  • Hypoglycemic activity: Rats with alloxan-induced diabetes mellitus treated with berberine had significantly lower blood sugar concentrations than control rats.19 Berberine also improved insulin resistance and liver glycogen levels similarly to metformin when given to rats fed a high fat diet.18 It is unclear whether bayberry exhibits the same effects.
  • Immunomodulating activity: An in vivo study was conducted using mice to test the immunosuppressant effects of berbamine at doses of 25mg/kg daily and 50mg/kg daily compared to control.86 With higher doses of berbamine, more splenic cells were suppressed; statistically significant when the mitogen is concanacalin A (ConA) at both doses and at 50mg/kg delay the mixed lymphocyte reaction (MLR) (p<0.01). Berbamine wash shown to significantly inhibit mitogen induced lymphocyte transformation (p<0.01).34
  • Berbamine 10μg/mL has been shown to inhibit neutrophil adherence and chemotaxis (p<0.05).34 Berbamine was also shown to suppress the uptake of neutrophil locomotion and neutrophil deoxyglucose uptake (p<0.05).
  • An in vivo study investigated the effects of berbamine on T-cell mediated immunity judged by delayed type hypersensitivity response (DTH) and mixed lymphocyte reaction (MLR).87 Four arms existed in the study: control, berbamine 25mg/kg daily, berbamine 50mg/kg daily, and cyclosporin 20mg/kg daily. High doses of berbamine showed a statistically significant difference in the MLR when compared to control (p<0.01). In regard to the DTH, both cyclosporin and high dose berbamine showed statistical significance (p<0.01) and the low dose berbamine just reach statistical significance (p=0.05).
  • In an in vitro study, berberine's effect on T-cell mediation was studied.88 T-cell effect was measured by the induction and development of adjuvant-induced arthritis in compromised hosts infected with Candida albicans.
  • Berbamine at 40mg/kg daily was shown to significantly decrease the total white blood cell infiltration while lowering polymorphonuclear leukocytes.35 At 80mg/kg daily, berbamine significantly reduced mononuclear leukocyte counts as well. A trend towards dose dependent inhibition of tumor necrosis factor and platelet activating factor was shown with the administration of berbamine.
  • Leukogenic activity: Berbamine, a derivative of barberry, has been shown in studies to have leukogenic effects in rats and dogs.60 In mice, combination therapy of cyclophosphamide 60mg/kg on day 1, 20mg/kg on days 8 and 11, and 30mg/kg on days 14 and 18, and berbamine 20mg/kg once daily for 21 days, or monotherapy with cyclophosphamide alone were administered to see the effects on white cell counts at day 14, day 21, and 7 days after end of treatment. The combination therapy group had significantly more white blood cells than then control at each monitoring interval (p<0.05).60 In dogs, a similar study was conducted and there was a trend towards the cyclophosphamide and berbamine arm, however, no statistic significance was shown.60 It is unclear whether the effects can be attributed solely to berberine.
  • Muscle relaxant activity: In an animal study, berberine sulphate (20mcg/mL) pretreatment blocked the response of ileum, trachea and rectal muscles to acetylcholine.89
  • Berberine inhibited muscle contractions of the guinea pig ileum and rat uterus induced by acetylcholine, carbachol, histamine, potassium chloride and bradykinin.23
  • Berberine was shown to increase the amplitude of slow-response action potentials induced by histamine by 6.2%; increase the maximum rate of depolarization by 21.1%; increase the action potential duration (APD) by 50.1% (APD 50) and 47.2% (APD 100) and effective refractory period by 92.2%.29
  • Osteoporosis activity: Berberine has been shown to inhibit parathyroid hormone-stimulated bone resorption in animal study.24 Berberine, in doses of 30 to 50mg/kg daily, has demonstrated an ability to prevent a decrease in bone mineral density of lumbar vertebra in ovariectomized rats and induce apoptosis of osteoclastic cells.24
  • Sedative activity: In animal study, berberine, an active ingredient in barberry, produced sedation and potentiated the sedative effects of pentobarbitone when administered via the intraperitoneal or intraventricular routes.32
  • Berberine has been shown to lower rectal temperature, reduce spontaneous motor activity and prolong hexobarbitone-induced sleeping time when administered to mice.23

Pharmacodynamics/Kinetics:
  • No pharmacokinetic data of barberry is available for humans. However, in humans, the oral administration of 1.2g berberine significantly delayed small intestinal transit time.25
  • Absorption: After receiving 500mg/kg of berberine, the whole blood concentrations were 0.8μg/mL at 8 hours in infant rabbits.90 According to the hazardous substance data bank, berberine is able to be absorbed through skin.
  • Metabolism: Muscles and liver reach peak berberine concentration after 12 hours.
  • Distribution: In rats, at a dose of 0.1g/kg taken orally, the area under the curve (AUC) is 0.713 ± 0.116mcg?h/mL, serum concentration maximum (Cmax) is 0.083 ± 0.007mcg/mL, and time to maximum concentration (Tmax) is 2.4 ± 0.2 hours.91 The blood levels plateau at 4 to 24 hours.
  • Elimination: Based on unsubstantiated reports, the elimination half-life of berberine in rats, after oral and intraperitoneal administration, is between 5 and 6 hours. Peak urinary excretion of berberine is seen at 12 to 24 hours, while peak fecal excretion is seen after 48 hours. Berberine is excreted through urine and feces.90
  • Minimum inhibitory concentration (MIC): An in vitro study assessing the antibacterial activity of berberine found that an aqueous extract containing berberine had an MIC of 50(/mL versus Clostridium tetani.92 Berberine also inhibited the growth of Candida krusei with an MIC <4(/mL in vitro.93
  • The MIC of berberine sulfate for Streptococcus pyogenes was found to be 30mcg/mL; and, berberine was found to inhibit the adherence of S. pyogenes to epithelial cells, immobilized fibronectin and hexadecane at concentrations below the MIC.94 Subsequent in vitro study has found that berberine sulfate (1mg/mL) causes morphological changes in these organisms: nuclear chromatin clumping in E. histolytica after 24 hours of exposure; irregular shaped vacuoles in G. lamblia culture after three hours of incubation; and, and increased number of autophagic vacuoles in T. vaginalis culture.95
  • IC50: In an in vitro study, the antiplasmodial and cytotoxic activity of natural bisbenzylisoquinoline, a constituent of barberry, were studied.96 Berberine was shown to have an acceptable amount of activity against Plasmodium and an IC50 between 100 and 200.

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