|Molar mass||336.36122 g/mol|
|Melting point||145 °C (293 °F; 418 K)|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|what is: / ?)(|
Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants as Berberis [e.g. Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), Berberis aristata (tree turmeric)], Hydrastis canadensis (goldenseal), Xanthorhiza simplicissima (yellowroot), Phellodendron amurense (Amur cork tree), Coptis chinensis (Chinese goldthread 黄连素 or Huang Lian Su), Tinospora cordifolia, Argemone mexicana (prickly poppy), and Eschscholzia californica (Californian poppy). Berberine is usually found in the roots, rhizomes, stems, and bark.
Berberine was supposedly used in China as a broad-spectrum anti-microbial medicine by Shennong around 3000 BC. This first recorded use of Berberine is described in the ancient Chinese medical book The Divine Farmer's Herb-Root Classic.
Due to Berberine's strong yellow color, Berberis species were used to dye wool, leather, and wood. Wool is still dyed with berberine today in northern India. Under ultraviolet light, berberine shows a strong yellow fluorescence, so it is used in histology for staining heparin in mast cells. As a natural dye, berberine has a colour index of 75160.
- 1 Traditional use
- 2 Newer and experimental uses
- 3 Contraindications
- 4 Biosynthesis
- 5 See also
- 6 References
As a Chinese traditional medicine or dietary supplement, berberine has shown some activity against fungal infections, Candida albicans, yeast, parasites, and bacterial/viral infections. Berberine seems to exert synergistic effects with fluconazole even in drug-resistant C. albicans infections.
Berberine is considered antibiotic. When applied in vitro and in combination with methoxyhydnocarpin, an inhibitor of multidrug resistance pumps, berberine inhibits growth of Staphylococcus aureus and Microcystis aeruginosa, a toxic cyanobacterium.
Berberine prevents and suppresses proinflammatory cytokines, E-selectin, and genes, and increases adiponectin expression which partly explains its versatile health effects. Berberine is a nucleic acid-binding isoquinoline alkaloid with wide potential therapeutic properties.
Newer and experimental uses
Diabetes, dyslipidemias and cardiovascular conditions
During the last few decades, many studies have shown berberine has various beneficial effects on the cardiovascular system and significant anti-inflammatory activities. A Canadian report suggested berberine can effectively reduce intracellular superoxide levels in LPS-stimulated macrophages. Such a restoration of cellular redox by berberine is mediated by its selective inhibition of gp91phox expression and enhancement of SOD activity.
Berberine exerts up-regulating activity on both the low-density-lipoprotein receptor (LDLR) and the insulin receptor (InsR). This one-drug-multiple-target characteristic might be suitable for the treatment of metabolic syndrome.
Berberine has been shown to lower elevated blood glucose as effectively as metformin. The mechanisms of action include inhibition of aldose reductase, inducing glycolysis, preventing insulin resistance through increasing insulin receptor expression and acting like incretins. A new study suggested berberine may overcome insulin resistance via modulating key molecules in insulin signaling pathway, leading to increased glucose uptake in insulin-resistant cells.
Berberine might exert its insulinotropic effect in isolated rat islets by up-regulating the expression of hepatocyte nuclear factor 4 alpha, which probably acts solely or together with other HNFs to modulate glucokinase activity, rendering β cells more sensitive to glucose fluctuation and to respond more effectively to glucose challenge.
Berberine seems to inhibit human dipeptidyl peptidase-4 (DPP4), as well as the prodiabetic target human protein tyrosine phosphatase 1B (h-PTP 1B), which explain at least some of its antihyperglycemic activities. Berberine suppresses intestinal disaccharidases with beneficial metabolic effects in diabetic states.
A recent comprehensive metabonomics method, applied to 60 type 2 diabetics, suggested administration of berberine down-regulates the high level of free fatty acids which are known to be toxic to the pancreas and cause insulin resistance. These results suggest berberine might play a pivotal role in the treatment of type 2 diabetes, concluded the authors.
Berberine has been shown to boost the effects of metformin and 2,4-thiazolidinedione (TZD), and can partly replace the commercial drugs, which could lead to a reduction in toxicity and side effects of the latter.
Berberine inhibits FOXO1, which integrates insulin signaling with mitochondrial function. Inhibition of Foxo1 can improve hepatic metabolism during insulin resistance and the metabolic syndrome.
Berberine lowers elevated blood total cholesterol, LDL cholesterol, triglycerides and atherogenic apolipoproteins (apo B) (Apo B), but the mechanism of action is distinct from that of statins. Berberine reduces LDL cholesterol by upregulating LDLR mRNA expression posttranscriptionally while downregulating the transcription of proprotein convertase subtilisin/kexin type 9 (PCSK9), a natural inhibitor of LDL receptor (LDLR), and increasing in the liver the expression of LDL receptors through extracellular signal-regulated kinase (ERK) signaling pathway, while statins inhibit cholesterol synthesis in the liver by blocking HMG-CoA-reductase. This explains why berberine does not cause side effects typical of statins. Berberine and plant stanols synergistically inhibit cholesterol absorption in hamsters.
Berberine seems to improve the arterial endothelial function in humans. Berberine activates AMP-activated protein kinase (AMPK), specifically extracellular signal-regulated kinases (ERK), which plays a central role in glucose and lipid metabolism, suppresses proinflammatory cytokines, and reduces MMP-9 and EMMPRIN expression, which are all beneficial changes for heart health.
Berberine reduces hepatic fat content in rats with nonalcoholic fatty liver disease. Berberine also prevents proliferation of hepatic stellate cells (HSCs), which are central for the development of fibrosis during liver injury.
Congestive heart failure
According to a Chinese report, combined use of berberine with cyclosporin A (CsA) could markedly increase the blood concentration of CsA and reduce the dosage of CsA required, save the cost for medical service, and shows no obvious adverse reaction in heart-transplant recipients.
Berberine has drawn extensive attention towards its antineoplastic effects. It seems to suppress the growth of a wide variety of tumor cells, including breast cancer, leukemia, melanoma, epidermoid carcinoma, hepatoma, pancreatic cancer, oral carcinoma, tongue carcinoma, glioblastoma, prostate carcinoma and gastric carcinoma. Animal studies have shown that berberine can suppress chemical-induced carcinogenesis, clastogenesis, tumor promotion, tumor invasion, prostate cancer, neuroblastoma, and leukemia.
It is a radiosensitizer of tumor cells, but not of normal cells. How berberine mediates these effects is not fully understood, but its ability to inhibit angiogenesis and to modulate Mcl-1, Bcl-xL, cyclooxygenase (COX)-2, MDR, tumor necrosis factor (TNF)- and IL-6, iNOS, IL-12, intercellular adhesion molecule-1 and ELAM-1 expression, MCP-1 and CINC-1, cyclin D1, activator protein (AP-1), HIF-1, PPAR-, and topoisomerase II has been shown. By using yeast mutants, berberine was found to bind and inhibit stress-induced mitogen-activated protein kinase kinase activation. Because apoptotic, carcinogenic, and inflammatory effects and various gene products (such as TNF-α, IL-6, COX-2, adhesion molecules, cyclin D1, and MDR) modulated by berberine are regulated by the transcription factor nuclear factor- B (NF- B), it is postulated this pathway plays a major role in the action of berberine. Berberine suppressed NF-κB activation induced by various inflammatory agents and carcinogens. This alkaloid also suppressed constitutive NF-κB activation found in certain tumor cells. It seems to protect against side effects of radiation therapy in lung cancer. However, new studies suggest that while berberine decreases cell growth, it increases the side population (stem cell) fraction of H460 lung cancer cells. In lung cancer it can also act through suppression of TGF-β1-induced epithelial-to-mesenchymal transition. Berberine enhances chemosensitivity to some chemotherapeutic agents like irinotecan .
Berberine, 300 mg three times a day orally, also seems to inhibit complication of abdominal or pelvic radiation, called radiation-induced acute intestinal symptoms. The studies suggest its use in clinical development may be more as a cytostatic agent than a cytotoxic compound.
Berberine seems to act as an herbal antidepressant and a neuroprotector against neurodegenerative disorders. Berberine inhibits prolyl oligopeptidase (POP) in a dose-dependent manner. Berberine is also known to bind to sigma receptors like many synthetic antidepressant drugs. As berberine is a natural compound that has been safely administered to humans, preliminary results suggest the initiation of clinical trials in patients with depression, bipolar affective disorder, schizophrenia, or related diseases in which cognitive capabilities are affected, with either the extract or pure berberine. New experimental results suggest berberine may have a potential for inhibition and prevention of Alzheimer's disease (AD), mainly through both cholinesterase (ChEs) inhibitory and β-amyloids pathways, and additionally through antioxidant capacities.
Other studies have shown berberine to increase noradrenaline and serotonin levels in the brain (rats) while inhibiting dopaminergic activity. The half-life of berberine in vivo seems to be three to four hours, thus suggesting administration three times a day if steady levels are to be achieved.
Berberine can ameliorate proinflammatory cytokines-induced intestinal epithelial tight junction damage in vitro, and berberine may be one of the targeted therapeutic agents that can restore barrier function in intestinal disease states.
A new study identified a key cellular mechanism underlying the protective effect of berberine on HIV PI-induced inflammatory response in macrophages. Modulation of the endoplasmic reticulum stress response represents a potential therapeutic target for various inflammatory diseases and metabolic syndromes, including HIV PI-associated atherosclerosis. The report shows the potential application of berberine as a complementary therapeutic agent for HIV/AIDS.
Berberine use in newborns has been associated with kernicterus, a bilirubin-induced brain dysfunction. Also, at dosages about 60-100 times as large as a human pharmacological dose, a small dose-response teratogenic effect was observed in rodents. For these reasons, berberine is not usually recommended for use during pregnancy, although there are some reason to believe that this may not be harmful.
The alkaloid berberine has a tetracyclic skeleton derived from a benzyltetrahydroisoquinoline system with the incorporation of an extra carbon atom provided by S-adenosyl methionine (SAM) via an N-methyl group. Formation of the berberine bridge is readily rationalized as an oxidative process in which the N-methyl group is oxidized to an iminium ion, and a cyclization to the aromatic ring occurs by virtue of the phenolic group.
Reticuline is known as the immediate precursor of protoberberine alkaloids in plants. Berberine is an alkaloid derived from tyrosine. L-DOPA and 4-hydroxypyruvic acid both come from L-Tyr. Although two tyrosine molecules are used in the biosynthetic pathway, only the phenylethylamine fragment of the tetrahydroisoquinoline ring system is formed via DOPA, the remaining carbon atoms come from tyrosine via 4-hydroxyphenylacetaldehyde. L-DOPA loses carbon dioxide to form dopamine 1. Likewise, 4-hydroxypyruvic acid also loses carbon dioxide to form 4-hydroxyphenyl-acetaldehyde 2. Dopamine 1 then reacts with 4-hydroxy-phenylacetaldehyde 2 to form (S)-norcolaurine 3 in a reaction similar to the Mannich reaction. After oxidation and methylation by SAM, (S)-reticuline 4 is formed. (S)-reticuline serves as a pivotal intermediate to other alkaloids. Oxidation of the tertiary amine then occurs and an iminium ion is formed 5. In a Mannich-like reaction the ortho position to the phenol is nucleophilic, and electrons are pushed to form 6. Product 6 then undergoes keto-enol tautomerism to form (S)-scoulerine, which is then methylated by SAM to form (S)-tetrahydrocolumbamine 7. Product 7 is then oxidized to form the methylenedioxy ring from the ortho-methoxyphenol, via an O2-, NADPH- and cytochrome P-450-dependent enzyme, giving (S)-canadine 8. (S)-canadine is then oxidized to give the quaternary isoquinolinium system of berberine. This happens in two separate oxidation steps, both requiring molecular oxygen, with H2O2 and H2O produced in the successive processes.
- Sanguinarine, a plant-based compound with very similar chemical classification as berberine
- Coptisine for a related pharmacological discussion
- Goldenseal for a related pharmacological discussion
- Jatrorrhizine another protoberberine alkaloid
- The Merck Index, 10th Ed. (1983), p.165, Rahway: Merck & Co.
- Zhang Q, Cai L, Zhong G, Luo W (2010). "Simultaneous determination of jatrorrhizine, palmatine, berberine, and obacunone in Phellodendri Amurensis Cortex by RP-HPLC". Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 35 (16): 2061–4. doi:10.4268/cjcmm20101603. PMID 21046728.
- Weiß, Dieter (2008). "Fluoreszenzfarbstoffe in der Natur" (in German). Retrieved 17 July 2009.
- "B3251 Berberine chloride form". Sigma-Aldrich. 2013. Retrieved 2 Aug 2013.
- Birdsall TC, Kelly GS (1997). "Berberine: Therapeutic potential of an alkaloid found in several medicinal plants" (PDF). Alternative Medicine Reviews 2 (2): 94–103.
- Gibbs PJ, Seddon KR (April 2000). "Berberine" (PDF). Alternative Medicine Review (British Library) 5 (2): 175–7. ISBN 0-7123-0649-8. PMID 10767672.
- Xu Y, Wang Y, Yan L, Liang RM, Dai BD, Tang RJ et al. (November 2009). "Proteomic analysis reveals a synergistic mechanism of fluconazole and berberine against fluconazole-resistant Candida albicans: endogenous ROS augmentation". Journal of Proteome Research 8 (11): 5296–304. doi:10.1021/pr9005074. PMID 19754040.
- Yu HH, Kim KJ, Cha JD, Kim HK, Lee YE, Choi NY et al. (2005). "Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus". Journal of Medicinal Food 8 (4): 454–61. doi:10.1089/jmf.2005.8.454. PMID 16379555.
- "Poster Presentations". FEBS Journal 277: 37. 2010. doi:10.1111/j.1742-4658.2010.07680.x.
- Li Y., Zuo G.-Y. 'Advances in studies on antimicrobial activities of alkaloids" Chinese Traditional and Herbal Drugs 2010 41:6 (1006-1014)
- Stermitz FR, Lorenz P, Tawara JN, Zenewicz LA, Lewis K (February 2000). "Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5'-methoxyhydnocarpin, a multidrug pump inhibitor". Proceedings of the National Academy of Sciences of the United States of America 97 (4): 1433–7. Bibcode:2000PNAS...97.1433S. doi:10.1073/pnas.030540597. PMC 26451. PMID 10677479.
- Zhang S, Zhang B, Xing K, Zhang X, Tian X, Dai W (2010). "Inhibitory effects of golden thread (Coptis chinensis) and berberine on Microcystis aeruginosa". Water Science & Technology 61 (3): 763. doi:10.2166/wst.2010.857. PMID 20150713.
- Babbar OP, Chhatwal VK, Ray IB, Mehra MK (December 1982). "Effect of berberine chloride eye drops on clinically positive trachoma patients". The Indian Journal of Medical Research 76 (Suppl): 83–8. PMID 7185757.
- Kalla, G.; Singhi, M.K.; Kalla, Gyaneshwar (1996). "Cutaneous leishmaniasis in Jodhpur district". Indian Journal of Dermatology, Venereology and Leprology 62 (3): 149–51.
- Hu Y, Chen X, Duan H, Hu Y, Mu X (2009). "Chinese herbal medicinal ingredients inhibit secretion of IL-6, IL-8, E-selectin and TXB2in LPS-induced rat intestinal microvascular endothelial cells". Immunopharmacology and Immunotoxicology 31 (4): 550–5. doi:10.3109/08923970902814129. PMID 19874221.
- Choi BH, Kim YH, Ahn IS, Ha JH, Byun JM, Do MS (2009). "The inhibition of inflammatory molecule expression on 3T3-L1 adipocytes by berberine is not mediated by leptin signaling". Nutrition Research and Practice 3 (2): 84–8. doi:10.4162/nrp.2009.3.2.84. PMC 2788178. PMID 20016706.
- Bhadra K, Kumar GS (2011). "Therapeutic potential of nucleic acid-binding isoquinoline alkaloids: Binding aspects and implications for drug design". Medicinal Research Reviews 31 (6): 821–62. doi:10.1002/med.20202. PMID 20077560.
- Kuo CL, Chi CW, Liu TY (January 2004). "The anti-inflammatory potential of berberine in vitro and in vivo". Cancer Lett 203 (2): 127–137. doi:10.1016/j.canlet.2003.09.002. PMID 14732220.
- Sarna LK, Wu N, Hwang SY, Siow YL, O K (2010). "Berberine inhibits NADPH oxidase mediated superoxide anion production in macrophages". Can J Physiol Pharmacol. 88 (3): 369–78. doi:10.1139/Y09-136. PMID 20393601.
- Yin J, Zhang H, Ye J (June 2008). "Traditional chinese medicine in treatment of metabolic syndrome". Endocrine, Metabolic & Immune Disorders Drug Targets 8 (2): 99–111. doi:10.2174/187153008784534330. PMC 2467395. PMID 18537696.
- Wang YX, Wang YP, Zhang H, Kong WJ, Li YH, Liu F et al. (November 2009). "Synthesis and biological evaluation of berberine analogues as novel up-regulators for both low-density-lipoprotein receptor and insulin receptor". Bioorganic & Medicinal Chemistry Letters 19 (21): 6004–8. doi:10.1016/j.bmcl.2009.09.059. PMID 19800225.
- Wang Y, Campbell T, Perry B, Beaurepaire C, Qin L (March 2010). "Hypoglycemic and insulin-sensitizing effects of berberine in high-fat diet- and streptozotocin-induced diabetic rats". Metabolism: Clinical and Experimental 60 (2): 298–305. doi:10.1016/j.metabol.2010.02.005. PMID 20304443.
- Wang C, Li J, Lv X, Zhang M, Song Y, Chen L et al. (August 2009). "Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high fat diet and streptozotocin". European Journal of Pharmacology 620 (1–3): 131–7. doi:10.1016/j.ejphar.2009.07.027. PMID 19686728.
- Gu Y, Zhang Y, Shi X, Li X, Hong J, Chen J et al. (May 2010). "Effect of traditional Chinese medicine berberine on type 2 diabetes based on comprehensive metabonomics". Talanta 81 (3): 766–72. doi:10.1016/j.talanta.2010.01.015. PMID 20298851.
- Zhang H, Wei J, Xue R, Wu JD, Zhao W, Wang ZZ et al. (September 2009). "Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression". Metabolism: Clinical and Experimental 59 (2): 285–92. doi:10.1016/j.metabol.2009.07.029. PMID 19800084.
- Wang JM, Yang Z, Xu MG, Chen L, Wang Y, Su C et al. (July 2009). "Berberine-induced decline in circulating CD31+/CD42- microparticles is associated with improvement of endothelial function in humans". European Journal of Pharmacology 614 (1–3): 77–83. doi:10.1016/j.ejphar.2009.04.037. PMID 19401197.
- Zhang Y, Li X, Zou D, Liu W, Yang J, Zhu N et al. (July 2008). "Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine". The Journal of Clinical Endocrinology and Metabolism 93 (7): 2559–65. doi:10.1210/jc.2007-2404. PMID 18397984.
- Yin J, Xing H, Ye J (May 2008). "Efficacy of berberine in patients with type 2 diabetes mellitus". Metabolism: Clinical and Experimental 57 (5): 712–7. doi:10.1016/j.metabol.2008.01.013. PMC 2410097. PMID 18442638.
- Wu LY, Ma ZM, Fan XL, Zhao T, Liu ZH, Huang X et al. (November 2009). "The anti-necrosis role of hypoxic preconditioning after acute anoxia is mediated by aldose reductase and sorbitol pathway in PC12 cells". Cell Stress & Chaperones 15 (4): 387–94. doi:10.1007/s12192-009-0153-6. PMC 3082650. PMID 19902381.
- Yin J, Gao Z, Liu D, Liu Z, Ye J (January 2008). "Berberine improves glucose metabolism through induction of glycolysis". American Journal of Physiology. Endocrinology and Metabolism 294 (1): E148–56. doi:10.1152/ajpendo.00211.2007. PMC 2464622. PMID 17971514.
- Kong WJ, Zhang H, Song DQ, Xue R, Zhao W, Wei J et al. (January 2009). "Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression". Metabolism 58 (1): 109–19. doi:10.1016/j.metabol.2008.08.013. PMID 19059538.
- Lou T, Zhang Z, Xi Z, et al. "Berberine Inhibits Inflammatory Response and Ameliorates Insulin Resistance in Hepatocytes." Inflammation. 2010 Nov 26.Abstract
- Lu SS, Yu YL, Zhu HJ, Liu XD, Liu L, Liu YW et al. (February 2009). "Berberine promotes glucagon-like peptide-1 (7-36) amide secretion in streptozotocin-induced diabetic rats". The Journal of Endocrinology 200 (2): 159–65. doi:10.1677/JOE-08-0419. PMID 18996945.
- Liu LZ, Cheung SC, Lan LL, Ho SK, Xu HX, Chan JC et al. (December 2009). "Berberine Modulates Insulin Signaling Transduction in Insulin-resistant Cells". Molecular and Cellular Endocrinology 317 (1–2): 148–53. doi:10.1016/j.mce.2009.12.027. PMID 20036710.
- Wang ZQ, Lu FE, Leng SH, Fang XS, Chen G, Wang ZS et al. (October 2008). "Facilitating effects of berberine on rat pancreatic islets through modulating hepatic nuclear factor 4 α expression and glucokinase activity". World journal of gastroenterology 14 (39): 6004–11. doi:10.3748/wjg.14.6004. PMC 2760199. PMID 18932278.
- Al-masri IM, Mohammad MK, Tahaa MO (July 2009). "Inhibition of dipeptidyl peptidase IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine". Journal of Enzyme Inhibition and Medicinal Chemistry 24 (5): 1061–6. doi:10.1080/14756360802610761. PMID 19640223.
- Liu L, Yu YL, Yang JS, Li Y, Liu YW, Liang Y et al. (March 2010). "Berberine suppresses intestinal disaccharidases with beneficial metabolic effects in diabetic states, evidences from in vivo and in vitro study". Naunyn-Schmiedeberg's Archives of Pharmacology 381 (4): 371–81. doi:10.1007/s00210-010-0502-0. PMID 20229011.
- Prabhakar PK, Doble M (August 2009). "Synergistic effect of phytochemicals in combination with hypoglycemic drugs on glucose uptake in myotubes". Phytomedicine 16 (12): 1119–26. doi:10.1016/j.phymed.2009.05.021. PMID 19660925.
- Sun X, Zhang X, Hu H, Lu Y, Chen J, Yasuda K et al. (September 2009). "Berberine inhibits hepatic stellate cell proliferation and prevents experimental liver fibrosis". Biological & Pharmaceutical Bulletin 32 (9): 1533–7. doi:10.1248/bpb.32.1533. PMID 19721228.
- Cheng Z, Guo S, Copps K, Dong X, Kollipara R, Rodgers JT et al. (November 2009). "Foxo1 integrates insulin signaling with mitochondrial function in the liver". Nature Medicine 15 (11): 1307–11. doi:10.1038/nm.2049. PMID 19838201.
- Zhou JY, Zhou SW, Zhang KB, Tang JL, Guang LX, Ying Y et al. (June 2008). "Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic hyperlipidemic rats". Biological & Pharmaceutical Bulletin 31 (6): 1169–76. doi:10.1248/bpb.31.1169. PMID 18520050.
- Holy EW, Akhmedov A, Lüscher TF, Tanner FC (February 2009). "Berberine, a natural lipid-lowering drug, exerts prothrombotic effects on vascular cells". Journal of Molecular and Cellular Cardiology 46 (2): 234–40. doi:10.1016/j.yjmcc.2008.10.011. PMID 19014947.
- Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C et al. (December 2004). "Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins". Nature Medicine 10 (12): 1344–51. doi:10.1038/nm1135. PMID 15531889.
- Kim WS, Lee YS, Cha SH, Jeong HW, Choe SS, Lee MR et al. (April 2009). "Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity". American Journal of Physiology– Endocrinology and Metabolism 296 (4): E812–9. doi:10.1152/ajpendo.90710.2008. PMID 19176354.
- Li H, Dong B, Park SW, Lee HS, Chen W, Liu J (August 2009). "HNF1α plays a critical role in PCSK9 gene transcription and regulation by a natural hypocholesterolemic compound berberine". The Journal of Biological Chemistry 284 (42): 28885–95. doi:10.1074/jbc.M109.052407. PMC 2781434. PMID 19687008.
- Abidi P, Zhou Y, Jiang JD, Liu J (October 2005). "Extracellular signal-regulated kinase-dependent stabilization of hepatic low-density lipoprotein receptor mRNA by herbal medicine berberine". Arteriosclerosis, Thrombosis, and Vascular Biology 25 (10): 2170–6. doi:10.1161/01.ATV.0000181761.16341.2b. PMID 16100034.
- Wang Y, Jia X, Ghanam K, Beaurepaire C, Zidichouski J, Miller L (2009). "Berberine and plant stanols synergistically inhibit cholesterol absorption in hamsters". Atherosclerosis 209 (1): 111–7. doi:10.1016/j.atherosclerosis.2009.08.050. PMID 19782362.
- Wang Y, Huang Y, Lam KS, Li Y, Wong WT, Ye H et al. (June 2009). "Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase". Cardiovascular Research 82 (3): 484–92. doi:10.1093/cvr/cvp078. PMID 19251722.
- Turner N, Li JY, Gosby A, To SW, Cheng Z, Miyoshi H et al. (May 2008). "Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action". Diabetes 57 (5): 1414–8. doi:10.2337/db07-1552. PMID 18285556.
- Cui G, Qin X, Zhang Y, Gong Z, Ge B, Zang YQ (August 2009). "Berberine differentially modulates the activities of Erk, p38 MAPK and JNK to suppress Th17 and Th1 T cell differentiation in type 1 diabetic mice". The Journal of Biological Chemistry 284 (41): 28420–9. doi:10.1074/jbc.M109.012674. PMC 2788891. PMID 19661066.
- Lamontagne J, Pepin E, Peyot ML, Joly E, Ruderman NB, Poitout V et al. (April 2009). "Pioglitazone acutely reduces insulin secretion and causes metabolic deceleration of the pancreatic β-cell at submaximal glucose concentrations". Endocrinology 150 (8): 3465–74. doi:10.1210/en.2008-1557. PMC 2717855. PMID 19406947.
- Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y et al. (August 2006). "Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states". Diabetes 55 (8): 2256–64. doi:10.2337/db06-0006. PMID 16873688.
- Jeong HW, Hsu KC, Lee JW, Ham M, Huh JY, Shin HJ et al. (April 2009). "Berberine suppresses proinflammatory responses through AMPK activation in macrophages". American Journal of Physiology– Endocrinology and Metabolism 296 (4): E955–64. doi:10.1152/ajpendo.90599.2008. PMID 19208854.
- Huang Z, Wang L, Meng S, Wang Y, Chen T, Wang C (July 2009). "Berberine reduces both MMP-9 and EMMPRIN expression through prevention of p38 pathway activation in PMA-induced macrophages". International Journal of Cardiology 146 (2): 153–158. doi:10.1016/j.ijcard.2009.06.023. PMID 19576641.
- Chang X, Yan H, Fei J, Jiang M, Zhu H, Lu D et al. (September 2010). "Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats" (PDF). The Journal of Lipid Research 51 (9): 2504–2515. doi:10.1194/jlr.m001958. PMID 20567026.
- Qi MY, Feng Y, Dai DZ, Li N, Cheng YS, Dai Y (February 2010). "CPU86017, a berberine derivative, attenuates cardiac failure through normalizing calcium leakage and downregulated phospholamban and exerting antioxidant activity". Acta Pharmacol Sin 31 (2): 165–74. doi:10.1038/aps.2009.180. PMC 4002834. PMID 20139899.
- Huang WM, Yan H, Jin JM, Yu C, Zhang H (December 1992). "Beneficial effects of berberine on hemodynamics during acute ischemic left ventricular failure in dogs". Chinese Medical Journal 105 (12): 1014–9. PMID 1299549.
- Riccioppo Neto F (February 1993). "Electropharmacological effects of berberine on canine cardiac Purkinje fibres and ventricular muscle and atrial muscle of the rabbit". British Journal of Pharmacology 108 (2): 534–7. doi:10.1111/j.1476-5381.1993.tb12836.x. PMC 1908004. PMID 8448600.
- Marin-Neto JA, Maciel BC, Secches AL, Gallo Júnior L (April 1988). "Cardiovascular effects of berberine in patients with severe congestive heart failure". Clinical Cardiology 11 (4): 253–60. doi:10.1002/clc.4960110411. PMID 3365876.
- Zeng XH, Zeng XJ, Li YY (July 2003). "Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy". The American Journal of Cardiology 92 (2): 173–6. doi:10.1016/S0002-9149(03)00533-2. PMID 12860219.
- Wu M., Wang J., Liu L.-T. "Advance of studies on anti-atherosclerosis mechanism of berberine", Chinese Journal of Integrative Medicine 2010 16:2 (188-192)
- Huang XS, Yang GF, Pan YC (August 2008). "[Effect of berberin hydrochloride on blood concentration of cyclosporine A in cardiac transplanted recipients]". Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi (in Chinese) 28 (8): 702–4. PMID 18928093.
- Sun Y, Xun K, Wang Y, Chen X (October 2009). "A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs". Anticancer Drugs 20 (9): 757–69. doi:10.1097/CAD.0b013e328330d95b. PMID 19704371.
- Tang J, Feng Y, Tsao S, Wang N, Curtain R, Wang Y (August 2009). "Berberine and Coptidis Rhizoma as novel antineoplastic agents: a review of traditional use and biomedical investigations". Journal of Ethnopharmacology 126 (1): 5–17. doi:10.1016/j.jep.2009.08.009. PMID 19686830.
- Kim JB, Yu JH, Ko E, Lee KW, Song AK, Park SY et al. (October 2009). "The alkaloid Berberine inhibits the growth of Anoikis-resistant MCF-7 and MDA-MB-231 breast cancer cell lines by inducing cell cycle arrest". Phytomedicine 17 (6): 436–40. doi:10.1016/j.phymed.2009.08.012. PMID 19800775.
- Serafim TL, Oliveira PJ, Sardao VA, Perkins E, Parke D, Holy J (May 2008). "Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line". Cancer Chemotherapy and Pharmacology 61 (6): 1007–18. doi:10.1007/s00280-007-0558-9. PMID 17661039.
- Pinto-Garcia L, Efferth T, Torres A, Hoheisel JD, Youns M (May 2010). "Berberine Inhibits Cell Growth and Mediates Caspase-Independent Cell Death in Human Pancreatic Cancer Cells". Planta Medica 76 (11): 1155–61. doi:10.1055/s-0030-1249931. PMID 20455200.
- Ho YT, Lu CC, Yang JS, Chiang JH, Li TC, Ip SW et al. (October 2009). "Berberine induced apoptosis via promoting the expression of caspase-8, -9 and -3, apoptosis-inducing factor and endonuclease G in SCC-4 human tongue squamous carcinoma cancer cells". Anticancer Research 29 (10): 4063–70. PMID 19846952.
- Auyeung KK, Ko JK (October 2009). "Coptis chinensis inhibits hepatocellular carcinoma cell growth through nonsteroidal anti-inflammatory drug-activated gene activation". International journal of molecular medicine 24 (4): 571–7. doi:10.3892/ijmm_00000267. PMID 19724899.
- Tang F, Wang D, Duan C, Huang D, Wu Y, Chen Y et al. (October 2009). "Berberine inhibits metastasis of nasopharyngeal carcinoma 5-8F cells by targeting Rho kinase-mediated Ezrin phosphorylation at threonine 567". The Journal of Biological Chemistry 284 (40): 27456–66. doi:10.1074/jbc.M109.033795. PMC 2785675. PMID 19651779.
- Sindhu G, Manoharan S (April 2010). "Anti-Clastogenic Effect of Berberine against DMBA-Induced Clastogenesis". Basic Clin Pharmacol Toxicol. 107 (4): 818–24. doi:10.1111/j.1742-7843.2010.00579.x. PMID 20406204.
- Pandey MK, Sung B, Kunnumakkara AB, Sethi G, Chaturvedi MM, Aggarwal BB (July 2008). "Berberine modifies cysteine 179 of IκBα kinase, suppresses nuclear factor-κB-regulated antiapoptotic gene products, and potentiates apoptosis". Cancer Research 68 (13): 5370–9. doi:10.1158/0008-5472.CAN-08-0511. PMID 18593939.
- Kim JB, Ko E, Han W, Shin I, Park SY, Noh DY (November 2008). "Berberine diminishes the side population and ABCG2 transporter expression in MCF-7 breast cancer cells". Planta Medica 74 (14): 1693–700. doi:10.1055/s-0028-1088313. PMID 18951337.
- Kim S, Choi JH, Kim JB, Nam SJ, Yang JH, Kim JH et al. (2008). "Berberine suppresses TNF-α-induced MMP-9 and cell invasion through inhibition of AP-1 activity in MDA-MB-231 human breast cancer cells". Molecules 13 (12): 2975–85. doi:10.3390/molecules13122975. PMID 19052522.
- Liu J, He C, Zhou K, Wang J, Kang JX (January 2009). "Coptis extracts enhance the anticancer effect of estrogen receptor antagonists on human breast cancer cells". Biochemical and Biophysical Research Communications 378 (2): 174–8. doi:10.1016/j.bbrc.2008.10.169. PMC 3454467. PMID 19000652.
- Thirupurasundari CJ, Padmini R, Devaraj SN (February 2009). "Effect of berberine on the antioxidant status, ultrastructural modifications and protein bound carbohydrates in azoxymethane-induced colon cancer in rats". Chemico-biological Interactions 177 (3): 190–5. doi:10.1016/j.cbi.2008.09.027. PMID 18951886.
- Mantena SK, Sharma SD, Katiyar SK (February 2006). "Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells". Molecular Cancer Therapeutics 5 (2): 296–308. doi:10.1158/1535-7163.MCT-05-0448. PMID 16505103.
- Muralimanoharan SB, Kunnumakkara AB, Shylesh B, Kulkarni KH, Haiyan X, Ming H et al. (April 2009). "Butanol fraction containing berberine or related compound from nexrutine inhibits NFκB signaling and induces apoptosis in prostate cancer cells". The Prostate 69 (5): 494–504. doi:10.1002/pros.20899. PMC 2674392. PMID 19107816.
- Choi MS, Oh JH, Kim SM, Jung HY, Yoo HS, Lee YM et al. (May 2009). "Berberine inhibits p53-dependent cell growth through induction of apoptosis of prostate cancer cells". International Journal of Oncology 34 (5): 1221–30. PMID 19360335.
- Wang GY, Lv QH, Dong Q, Xu RZ, Dong QH (2009). "Berbamine induces Fas-mediated apoptosis in human hepatocellular carcinoma HepG2 cells and inhibits its tumor growth in nude mice". Journal of Asian Natural Products Research 11 (3): 219–28. doi:10.1080/10286020802675076. PMID 19408145.
- Choi MS, Yuk DY, Oh JH, Jung HY, Han SB, Moon DC et al. (November 2008). "Berberine inhibits human neuroblastoma cell growth through induction of p53-dependent apoptosis". Anticancer Research 28 (6A): 3777–84. PMID 19189664.
- Lin CC, Ng LT, Hsu FF, Shieh DE, Chiang LC (January 2004). "Cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents (berberine, coptisine and icariin) on hepatoma and leukaemia cell growth". Clin. Exp. Pharmacol. Physiol. 31 (1–2): 65–9. doi:10.1111/j.1440-1681.2004.03951.x. PMID 14756686.
- Lin CC, Lin SY, Chung JG, Lin JP, Chen GW, Kao ST (March 2006). "Down-regulation of cyclin B1 and up-regulation of Wee1 by berberine promotes entry of leukemia cells into the G2/M-phase of the cell cycle". Anticancer Research 26 (2A): 1097–104. PMID 16619512.
- Khan M, Giessrigl B, Vonach C, Madlener S, Prinz S, Herbaceck I et al. (January 2010). "Berberine and a Berberis lycium extract inactivate Cdc25A and induce α-tubulin acetylation that correlate with HL-60 cell cycle inhibition and apoptosis". Mutation Research 683 (1–2): 123–30. doi:10.1016/j.mrfmmm.2009.11.001. PMID 19909759.
- Lin S, Tsai SC, Lee CC, Wang BW, Liou JY, Shyu KG (1 September 2004). "Berberine inhibits HIF-1α expression via enhanced proteolysis". Molecular Pharmacology 66 (3): 612–9. doi:10.1124/mol.66.3 (inactive 2015-01-10). PMID 15322253.
- Liu Y, Yu H, Zhang C, Cheng Y, Hu L, Meng X et al. (November 2008). "Protective effects of berberine on radiation-induced lung injury via intercellular adhesion molecular-1 and transforming growth factor-β-1 in patients with lung cancer". European Journal of Cancer 44 (16): 2425–32. doi:10.1016/j.ejca.2008.07.040. PMID 18789680.
- Qi HW, Xin LY, Xu X, Ji XX, Fan LH (Jan 2014). "Epithelial-to-mesenchymal transition markers to predict response of Berberine in suppressing lung cancer invasion and metastasis". J Transl Med. 12: 22. doi:10.1186/1479-5876-12-22. PMC 3944941. PMID 24456611.
- Yu M, Tong X, Qi B, Qu H, Dong S, Yu B et al. (Jan 2014). "Berberine enhances chemosensitivity to irinotecan in colon cancer via inhibition of NF-κB". J Mol Med Rep 9 (1): 249–54. doi:10.3892/mmr.2013.1762. PMID 24173769.
- Li GH, Wang DL, Hu YD, Pu P, Li DZ, Wang WD et al. (September 2009). "Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy". Medical Oncology (Northwood, London, England) 27 (3): 919–25. doi:10.1007/s12032-009-9307-8. PMID 19757213.
- Kulkarni SK, Dhir A (July 2009). "sigma-1 receptors in major depression and anxiety". Expert Review of Neurotherapeutics 9 (7): 1021–34. doi:10.1586/ern.09.40. PMID 19589051.
- Kulkarni SK, Dhir A (June 2009). "Current investigational drugs for major depression". Expert Opinion on Investigational Drugs 18 (6): 767–88. doi:10.1517/13543780902880850. PMID 19426122.
- Kulkarni SK, Dhir A (July 2008). "On the mechanism of antidepressant-like action of berberine chloride". European Journal of Pharmacology 589 (1–3): 163–72. doi:10.1016/j.ejphar.2008.05.043. PMID 18585703.
- Kulkarni SK, Dhir A (December 2009). "Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders". Phytotherapy Research 24 (3): 317–24. doi:10.1002/ptr.2968. PMID 19998323.
- Xiang J, Yu C, Yang F; Yu; Yang; Yang; Ding (December 2009). "Conformation-activity studies on the interaction of berberine with acetylcholinesterase: Physical chemistry approach". Progress in Natural Science 19 (12): 1721–5. doi:10.1016/j.pnsc.2009.07.010.
- Huang L, Shi A, He F, Li X (December 2009). "Synthesis, biological evaluation, and molecular modeling of berberine derivatives as potent acetylcholinesterase inhibitors". Bioorganic & Medicinal Chemistry 18 (3): 1244–51. doi:10.1016/j.bmc.2009.12.035. PMID 20056426.
- Jung HA, Min BS, Yokozawa T, Lee JH, Kim YS, Choi JS (August 2009). "Anti-Alzheimer and antioxidant activities of Coptidis Rhizoma alkaloids". Biological & Pharmaceutical Bulletin 32 (8): 1433–8. doi:10.1248/bpb.32.1433. PMID 19652386.
- Peng WH, Lo KL, Lee YH, Hung TH, Lin YC (August 2007). "Berberine produces antidepressant-like effects in the forced swim test and in the tail suspension test in mice". Life Sciences 81 (11): 933–938. doi:10.1016/j.lfs.2007.08.003. PMID 17804020.
- Lee B, Yang CH, Hahm DH, Choe ES, Lee HJ, Pyun KH et al. (October 2007). "Inhibitory Effects of Coptidis rhizoma and Berberine on Cocaine-induced Sensitization". Evidence-based Complementary and Alternative Medicine 6 (1): 85–90. doi:10.1093/ecam/nem070. PMC 2644267. PMID 18955248.
- Zhao YN, Ding Y, Wang RF, Xing DM, Cheng J, Du L (2004). "A new approach to investigate the pharmacokinetics of traditional chinese medicine YL2000". The American journal of Chinese Medicine 32 (6): 921–929. doi:10.1142/S0192415X04002521. PMID 15673197.
- Li N, Gu L, Qu L, Gong J, Li Q, Zhu W et al. (2010). "Berberine attenuates pro-inflammatory cytokine-induced tight junction disruption in an in vitro model of intestinal epithelial cells". European Journal of Pharmaceutical Sciences 40 (1): 1–8. doi:10.1016/j.ejps.2010.02.001. PMID 20149867.
- Gu L, Li N, Gong J, Li Q, Zhu W, Li J (2011). "Berberine ameliorates intestinal epithelial tight-junction damage and down-regulates myosin light chain kinase pathways in a mouse model of endotoxinemia". The Journal of infectious diseases 203 (11): 1602–12. doi:10.1093/infdis/jir147. PMID 21592990.
- Zha W, Liang G, Xiao J, Studer EJ, Hylemon PB, Pandak WM et al. (2010). Luo Y, ed. "Berberine Inhibits HIV Protease Inhibitor-Induced Inflammatory Response by Modulating ER Stress Signaling Pathways in Murine Macrophages". PLoS ONE 5 (2): e9069. Bibcode:2010PLoSO...5.9069Z. doi:10.1371/journal.pone.0009069. PMC 2817721. PMID 20161729.
- Chan E (1993). "Displacement of bilirubin from albumin by berberine". Biology of the neonate 63 (4): 201–8. doi:10.1159/000243932. PMID 8513024.
- Jahnke GD, Price CJ, Marr MC, Myers CB, George JD (2006). "Developmental toxicity evaluation of berberine in rats and mice". Birth Defects Res B Dev Reprod Toxicol 77 (3): 201–8. doi:10.1002/bdrb.20075. PMID 16634078.
- Linn YC, Lu J, Lim LC, Sun H, Sun J, Zhou Y et al. (2012). "Berberine-induced haemolysis revisited: safety of Rhizoma coptidis and Cortex phellodendri in chronic haematological diseases". Phytotherapy research 26 (5): 682–6. doi:10.1002/ptr.3617. PMID 22002596.
- Dewick, P. (2009). Medicinal Natural Products: A Biosynthetic Approach (3rd ed.). West Sussex, England: Wiley. p. 357. ISBN 0-471-49641-3.
- Park SU, Facchini PJ (June 2000). "Agrobacterium rhizogenes-mediated transformation of opium poppy, Papaver somniferum l., and California poppy, Eschscholzia californica cham., root cultures". Journal of Experimental Botany 51 (347): 1005–16. doi:10.1093/jexbot/51.347.1005. PMID 10948228.
- Dewick, P. (2009). Medicinal Natural Products: A Biosynthetic Approach (3rd ed.). West Sussex, England: Wiley. p. 358. ISBN 0-471-49641-3.