Scientific Name(s): Berberis aristata Sims., Berberis vulgaris L., Mahonia aquifolium (Pursh) Nutt.
Common Name(s): Barberry, Berberis, Holly barberry, Jaundice berry, Oregon barberry, Oregon grape, Oregon grapeholly, Pepperidge bush, Sour-spine, Sowberry, Trailing mahonia, Woodsour
Clinical applications may include use in treating diabetes and dyslipidemia, although clinical trials are limited and are often of poor quality. Other activity includes antimicrobial, antioxidant, and anti-inflammatory effects. No clinical trials exist to support uses related to effects on the cardiovascular and central nervous systems or treating cancer.
Daily doses of 2 g of the berries and 1.5 to 3 g daily of dry bark have been used; however, there are limited clinical studies to substantiate barberry's varied uses.
Caution is warranted in the presence of cardiac arrhythmia. Use in children has not been validated.
Avoid use. There are documented adverse effects, including uterine stimulant effects.
Case reports are lacking; however, barberry exhibits anti-cytochrome P450 3A4 (CYP3A4) activity similar to that of grapefruit. Caution is warranted with coadministration of potentially toxic medicines such as cyclosporine.
GI symptoms (eg, nausea, vomiting, diarrhea), dizziness, and fainting have been reported. Effects on the cardiovascular system (eg, hypotension, decreased heart rate) and decreased respiration may occur with high dosages. The German Commission E reports that lower doses of berberine are well tolerated. Hypersensitivity has been documented.
Symptoms of poisoning are characterized by lethargy, stupor and daze, vomiting and diarrhea, and nephritis. A median lethal dose (LD50) for berberine was noted as 27.5 mg/kg in humans. Berberine showed mutagenicity in yeast cells and Ames test, while a phototoxic reaction between berberine alkaloid and ultraviolet A (UVA) light has been described.
Some 500 species of barberry are recognized, and plants within the genus Berberis and Mahonia have similar chemical composition. Barberry grows wild throughout Europe but has been naturalized to many regions of the eastern US. M. aquifolium is an evergreen shrub native to the northwestern US and Canada. Barberry grows to more than 3 m with branched, spiny, holly-like leaves and is widely planted as an ornamental. Its yellow flowers bloom from May to June and develop into red to blue/black oblong berries.1, 2, 3, 4
Barberry has a long history of use, dating back to the Middle Ages in Europe. Salishan tribe native elders of the Pacific Northwest used M. aquifolium to treat acne, and Native Americans utilized Mahonia berries to treat scurvy. The species B. aristata has been used in traditional Chinese and Nepalese medicine and in the Ayurvedic medical system for many years. The sundried fruits are eaten for antipyretic and diuretic effects in Turkey. A decoction of the plant has been used to treat GI ailments and coughs. The alkaloid berberine was included as an astringent in eye drops, but its use has become rare. The edible fruits have been used to prepare jams, jellies, and juices. The use of the plant in traditional medicine has been limited by the bitter taste of the bark and root. However, multiple medicinal uses for barberry have been listed and include treatments in cancer, cholera, and hypertension.2, 3, 5
Plant parts include the stem, root, fruit, flowers, and leaves. Alkaloids, tannins, phenolic compounds, sterols, and triterpenes have all been described. The isoquinoline alkaloids are of primary interest and include berberine, berbamine, and oxycanthine, among numerous others. Variation in content exists among the different species. Methods for identification and quantification have been established and berberine fingerprinting has been described.2, 4, 6, 7, 8
Uses and Pharmacology
Alkaloids isolated from M. aquifolium exhibited anti-inflammatory and antiproliferative activity.2, 3
Limited clinical studies have evaluated the efficacy of topical M. aquifolium in psoriasis. Efficacy was greater than with placebo but not as effective as with standard therapy; exacerbations have been described. Further studies are required. 9
Because of the association of Helicobacter pylori with gastritis, peptic ulcer, and gastric cancer, in vitro experimentation was conducted in H. pylori-infected gastric epithelial cells with 24 medicinal plants indigenous to Pakistan to evaluate their effect on secretion of interleukin (IL)-8 and generation of reactive oxygen species (ROS) in order to assess anti-inflammatory and cytoprotective effects. Although no significant direct cytotoxic effects on the gastric cells or bactericidal effects on H. pylori were found, root extract of barberry was observed to have mild and moderate inhibitory activity on IL-8 at 50 and 100 mcg/mL, respectively, and the most significant suppression on ROS generation in H. pylori-infected gastric cells of extracts tested.9
Antimicrobial effects have been described for Berberis spp. and berberine.2, 10, 11 In mice, a topical 20% root bark extract application was effective against cutaneous leishmaniasis,12 while chickens with severe diarrhea fed B. vulgaris root bark extract fared better through anticoccidal activity.13
Older, limited clinical studies evaluated berberine for treating diarrhea caused by Eschericia coli and cholera, and against microbes such as giardia and trichomonas.14, 15
Induction of apoptosis and cell cycle arrest, signalling, and tumor promotion have been shown in vitro by B. vulgaris and B. aristata extracts, and berberine and berbamine constituents.7, 10, 16, 17
Research reveals no clinical data regarding the use of barberry for cancer. Berberine alone has been evaluated as an adjunct to prevent adverse effects of radiation.18
Experiments have shown berberine to exhibit effects on the cardiovascular system, although the mechanisms remain poorly understood. Positive inotropic and negative chronotropic effects, as well as vasodilatory, antiarrhythmic, and hypotensive effects, have been described.7, 19, 20
Research reveals no clinical data regarding the use of Berberis or Mahonia spp. for cardiovascular conditions. Caution is warranted in the presence of cardiac arrhythmia.
Anti-acetylcholinesterase activity has occurred for berberine and extracts of B. vulgaris in animal studies and in vitro experiments.10, 21, 22, 23, 24 In mice, neuroprotective effects have been demonstrated whereby berberine inhibited apoptosis in hippocampal tissue and prevented dopaminergic neuronal damage on histology. Improvements in short-term memory and enhanced motor balance and coordination were observed in a mouse model of Parkinson disease.24 An anticonvulsant effect was demonstrated in mice.21
Research reveals no clinical data regarding the use of Berberis or Mahonia spp. for CNS-related conditions.
Studies in rodents both normotensive and with induced diabetes have consistently demonstrated improved glycemic control with administration of berberine and Berberis extracts. Inhibition of alpha-glucosidase activity has been demonstrated; however, the precise mechanism of action remains unclear.10, 25, 26, 27, 28
Berberine exerted a hypoglycemic action in a small trial of patients with type 2 diabetes.29 In women with metabolic-associated polycystic ovary syndrome, berberine taken over 3 months decreased fasting blood glucose levels.30 Findings from a larger, multicenter clinical trial evaluating this effect have not been concluded.31 Small clinical trials examining the effect of consumption of the fruit in type 2 diabetes showed improvements in the lipid profile and glycemic control.28, 32 Data from trials in which Berberis extracts were used in combination with other plant extracts cannot be attributed to a single plant.33, 34, 35
Studies in rodents have shown positive effects of berberine on the lipid profile.10, 36
Berberine alone improved the lipid profile in dyslipidemia in several clinical trials among participants with differing conditions, including familial hypercholesterolemia, obesity, and diabetes.37, 38, 39 Barberry taken over 6 weeks improved the lipid profile and influenced C-reactive protein in a randomized clinical study in 106 patients with metabolic syndrome; effect on blood pressure or other cardiovascular outcomes was not reported.40 Small clinical trials have been conducted examining the effect of barberry consumption in type 2 diabetes and demonstrated improvements in the lipid profile and glycemic control.28, 32 In 124 euglycemic, dyslipidemic patients intolerant to high doses of statins, administration of half the statin dose plus twice daily dosing of a B. aristata 588 mg/S. marianum 105 mg combination product significantly reduced fasting plasma glucose, insulin, insulin index and stabilized lipid levels compared to baseline and placebo in a 6-month double-blind, randomized, placebo-controlled trial. Lipid levels increased significantly during the study period in the placebo group. The intervention (a patented nutraceutical in Italy containing B. aristata extract standardized to 85% berberine plus S. marianum extract titrated to more than 60% flavanolignans) was well tolerated.53
Limited studies in rodents and when using homeopathic doses suggest B. vulgaris extracts possess activity against calcium oxalate deposition.41, 42 B. aristata improved benign prostatic hyperplasia in rats possibly by inhibition of androgen and anti-inflammatory effects.22, 43 A small clinical trial reported positive effects for B. vulgaris fruit extract in treating acne. The study was conducted for only 4 weeks, with results from a longer trial required.44 The American Academy of Dermatology/American Academy of Dermatology Association guidelines of care for the management of acne vulgaris (2016) states that oral barberry has been reported to have value in the treatment of acne (limited; moderate).55
Antioxidant effects have been documented.45, 46 Effects on the GI tract have been described in rodent studies. Protection against inflammatory-related damage and motility effects have been reported, suggesting therapeutic uses for inflammatory bowel conditions.47, 48
Further effects for berberine alone have been described in studies using Goldenseal (see Goldenseal monograph).
Barberry berries and root bark have been used as a source of berberine. Daily doses of 2 g of the berries and 1.5 to 3 g daily of dry bark have been used3; however, there are limited clinical studies to substantiate barberry's varied uses.2, 49 Berberine and related alkaloids are poorly absorbed when taken orally; in vitro and animal studies must be interpreted with care. Use in children has not been validated.
Pregnancy / Lactation
Avoid use. There are documented adverse effects, including uterine stimulant effects.3, 49, 50
Case reports are lacking; however, Berberis exhibits anti-CYP3A4 activity similar to that of grapefruit. Caution is warranted with coadministration of potentially toxic medicines such as cyclosporine.19, 51 Berberine may also induce P-glycoprotein.56
GI symptoms (eg, nausea, vomiting, diarrhea), dizziness, and fainting have been reported. Effects on the cardiovascular system (eg, hypotension, decreased heart rate) and decreased respiration may occur with high dosages.2, 3 Hypersensitivity has been documented.9 The German Commission E reports that doses of berberine 500 mg are well tolerated.49
Symptoms of poisoning are characterized by lethargy, stupor and daze, vomiting and diarrhea, and nephritis.49 An LD50 for berberine was noted as 27.5 mg/kg in humans.8
Berberine showed mutagenicity in yeast cells and Ames test.3 A phototoxic reaction between berberine alkaloids and UVA light has been described.52
1. Berberis vulgaris
L. USDA, NRCS. 2014. The PLANTS database
, 2014). National Plant Data Team, Greensboro, NC 27401-4901 USA. Accessed September 25, 2014.
2. Khan IA, Abourashed EA. Leung’s Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics
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3. Duke JA. Handbook of Medicinal Herbs
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4. Mokhber-Dezfuli N, Saeidnia S, Gohari AR, Kurepaz-Mahmoodabadi M. Phytochemistry and pharmacology of Berberis
species. Pharmacogn Rev
5. Isikli ND, Yilmaz I. Some physical properties of sun-dried Berberis
fruit (Berberis crataegina
). J Food Sci Technol
6. Zovko Koncić M, Kremer D, Karlović K, Kosalec I. Evaluation of antioxidant activities and phenolic content of Berberis vulgaris
L. and Berberis croatica
Horvat. Food Chem Toxicol
7. Potdar D, Hirwani RR, Dhulap S. Phyto-chemical and pharmacological applications of Berberis aristata
8. Duke J. Dr. Duke's phytochemical and ethnobotanical databases. Agricultural Research Service website. http://www.ars-grin.gov/duke
. Updated June 13, 1996. Accessed September 25, 2014.
9. Deng S, May BH, Zhang AL, Lu C, Xue CC. Plant extracts for the topical management of psoriasis: a systematic review and meta-analysis. Br J Dermatol
10. Abd El-Wahab AE, Ghareeb DA, Sarhan EE, Abu-Serie MM, El Demellawy MA. In vitro biological assessment of Berberis vulgaris
and its active constituent, berberine: antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effects. BMC Complement Altern Med
11. Rouhani S, Salehi N, Kamalinejad M, Zayeri F. Efficacy of Berberis vulgaris
aqueous extract on viability of Echinococcus granulosus
protoscolices. J Invest Surg
12. Salehabadi A, Karamian M, Farzad MH, Namaei MH. Effect of root bark extract of Berberis vulgaris
L. on Leishmania major
on BALB/c mice. Parasitol Res
13. Malik TA, Kamili AN, Chishti MZ, Tanveer S, Ahad S, Johri RK. In vivo anticoccidial activity of berberine [18, 5,6-dihydro-9,10-dimethoxybenzo(g)-1,3-benzodioxolo(5,6-a) quinolizinium]—an isoquinoline alkaloid present in the root bark of Berberis lycium
14. Rabbani GH, Butler T, Knight J, Sanyal SC, Alam K. Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli
and Vibrio cholerae
. J Infect Dis
15. Kin-Maung U, Myo-Khin, Nyunt-Nyunt-Wai, Aye-Kyaw, Tin-U. Clinical trial of berberine in acute watery diarrhoea. Br Med J (Clin Res Ed)
16. Ho YT, Yang JS, Lu CC, et al. Berberine inhibits human tongue squamous carcinoma cancer tumor growth in a murine xenograft model. Phytomedicine
17. Yang F, Nam S, Brown CE, et al. A novel berbamine derivative inhibits cell viability and induces apoptosis in cancer stem-like cells of human glioblastoma, via up-regulation of miRNA-4284 and JNK/AP-1 signaling. PLoS One
18. Li GH, Wang DL, Hu YD, et al. Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy. Med Oncol
19. Brenyo A, Aktas MK. Review of complementary and alternative medical treatment of arrhythmias. Am J Cardiol
20. Lau CW, Yao XQ, Chen ZY, Ko WH, Huang Y. Cardiovascular actions of berberine. Cardiovasc Drug Rev
21. Bonesi M, Loizzo MR, Conforti F, et al. Berberis aetnensis
and B. libanotica
: a comparative study on the chemical composition, inhibitory effect on key enzymes linked to Alzheimer's disease and antioxidant activity. J Pharm Pharmacol
22. Bhutada P, Mundhada Y, Bansod K, Dixit P, Umathe S, Mundhada D. Anticonvulsant activity of berberine, an isoquinoline alkaloid in mice. Epilepsy Behav
23. Simões Pires EN, Frozza RL, Hoppe JB, Menezes Bde M, Salbego CG. Berberine was neuroprotective against an in vitro model of brain ischemia: survival and apoptosis pathways involved. Brain Res
24. Kim M, Cho KH, Shin MS, et al. Berberine prevents nigrostriatal dopaminergic neuronal loss and suppresses hippocampal apoptosis in mice with Parkinson's disease. Int J Mol Med
25. Moazezi Z, Qujeq D. Berberis fruit extract and biochemical parameters in patients with type II diabetes. Jundishapur J Nat Pharm Prod
26. El-Sayed MM, Ghareeb DA, Talat HA, Sarhan EM. High fat diet induced insulin resistance and elevated retinol binding protein 4 in female rats; treatment and protection with Berberis vulgaris
extract and vitamin A. Pak J Pharm Sci
27. Ashraf H, Heidari R, Nejati V, Ilkhanipoor M. Effects of aqueous extract of Berberis integerrima
root on some physiological parameters in streptozotocin-induced diabetic rats. Iran J Pharm Res
28. Meliani N, Dib Mel A, Allali H, Tabti B. Hypoglycaemic effect of Berberis vulgaris
L. in normal and streptozotocin-induced diabetic rats. Asian Pac J Trop Biomed
29. Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism
30. Wei W, Zhao H, Wang A, et al. A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome. Eur J Endocrinol
31. Li Y, Ma H, Zhang Y, et al. Effect of berberine on insulin resistance in women with polycystic ovary syndrome: study protocol for a randomized multicenter controlled trial. Trials
32. Shidfar F, Ebrahimi SS, Hosseini S, Heydari I, Shidfar S, Hajhassani G. The effects of Berberis vulgaris
fruit extract on serum lipoproteins, apoB, apoA-I, homocysteine, glycemic control and total antioxidant capacity in type 2 diabetic patients. Iran J Pharm Res
33. Di Pierro F, Villanova N, Agostini F, Marzocchi R, Soverini V, Marchesini G. Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control. Diabetes Metab Syndr Obes
34. Di Pierro F, Putignano P, Villanova N, Montesi L, Moscatiello S, Marchesini G. Preliminary study about the possible glycemic clinical advantage in using a fixed combination of Berberis aristata
and Silybum marianum
standardized extracts versus only Berberis aristata
in patients with type 2 diabetes. Clin Pharmacol
35. Derosa G, Bonaventura A, Bianchi L, et al. Berberis aristata
fixed combination on lipid profile and insulin secretion in dyslipidemic patients. Expert Opin Biol Ther
36. Zhou Y, Cao S, Wang Y, et al. Berberine metabolites could induce low density lipoprotein receptor up-regulation to exert lipid-lowering effects in human hepatoma cells. Fitoterapia
37. Pisciotta L, Bellocchio A, Bertolini S. Nutraceutical pill containing berberine versus ezetimibe on plasma lipid pattern in hypercholesterolemic subjects and its additive effect in patients with familial hypercholesterolemia on stable cholesterol-lowering treatment. Lipids Health Dis
38. Hu Y, Ehli EA, Kittelsrud J, et al. Lipid-lowering effect of berberine in human subjects and rats. Phytomedicine
39. Cianci A, Cicero AF, Colacurci N, Matarazzo MG, De Leo V. Activity of isoflavones and berberine on vasomotor symptoms and lipid profile in menopausal women. Gynecol Endocrinol
40. Zilaee M, Kermany T, Tavalaee S, Salehi M, Ghayour-Mobarhan M, Ferns GA. Barberry treatment reduces serum anti-heat shock protein 27 and 60 antibody titres and high-sensitivity C-reactive protein in patients with metabolic syndrome: a double-blind, randomized placebo-controlled trial. Phytother Res
41. Jyothilakshmi V, Thellamudhu G, Kumar A, Khurana A, Nayak D, Kalaiselvi P. Preliminary investigation on ultra high diluted B. vulgaris
in experimental urolithiasis. Homeopathy
42. Bashir S, Gilani AH, Siddiqui AA, et al. Berberis vulgaris
root bark extract prevents hyperoxaluria induced urolithiasis in rats. Phytother Res
43. Dumbre RK, Kamble MB, Patil VR. Inhibitory effects by ayurvedic plants on prostate enlargement induced in rats. Pharmacognosy Res
44. Fouladi RF. Aqueous extract of dried fruit of Berberis vulgaris
L. in acne vulgaris, a clinical trial. J Diet Suppl
45. Qujeq D, Kamei S. In vitro antioxidant effects of barberry fruit extracts. Int J Mol Cell Med
46. Sahin K, Orhan C, Tuzcu M, et al. Berberis vulgaris
root extract alleviates the adverse effects of heat stress via modulating hepatic nuclear transcription factors in quails. Br J Nutr
47. Minaiyan M, Ghannadi A, Mahzouni P, Jaffari-Shirazi E. Comparative study of Berberis vulgaris
fruit extract and berberine chloride effects on acetic acid-induced colitis in rats. Iran J Pharm Res
48. Chen DP, Xiong YJ, Lv BC, et al. Effects of berberine on rat jejunal motility. J Pharm Pharmacol
49. Blumenthal M, Goldberg A, Brinckmann J, eds. Herbal Medicine: Expanded Commission E Monographs
. Newton, MA: Integrative Medicine Communications; 2000.
50. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG
51. Chatuphonprasert W, Nemoto N, Sakuma T, Jarukamjorn K. Modulations of cytochrome P450 expression in diabetic mice by berberine. Chem Biol Interact
52. Inbaraj JJ, Kukielczak BM, Bilski P, Sandvik SL, Chignell CF. Photochemistry and photocytotoxicity of alkaloids from goldenseal (Hydrastis canadensis
L.) 1. Berberine. Chem Res Toxicol
53. Derosa G, Romano D, D’Angelo A, Maffioli P. Berberis aristata
combined with Silybum marianum
on lipid profile in patients not tolerating statins at high doses. Atherosclerosis
54. Zaidi SF, Muhammad JS, Shahryar S, et al. Anti-inflammatory and cytoprotective effects of selected Pakistani medicinal plants in Helicobacter pylori
-infected gastric epithelial cells. J Ethnopharmacol
55. Zaenglein AL, Pathy AL, Schlosser BJ, at al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945-973.e33.26897386
56. Dietie A, Hume AL. Berberine may be a promising botanical for glycemic control. Pharmacy Today
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