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Special Report

Metabolic and cardiovascular effects of berberine: from preclinical evidences to clinical trial results

Arrigo CiceroCorrespondence[email protected]
&
Sibel Ertek
Pages 553-563 | Published online: 18 Jan 2017

  • Müller‑Nordhorn J, Binting S, Roll S, Willich SN: An update on regional variation in cardiovascular mortality within Europe. Eur. Heart J. 29(10), 1316–1326 (2008).
  • Baigent C, Keech A, Kearney PM et al.; Cholesterol Treatment Trialists’ (CTT) Collaborators: efficacy and safety of cholesterol‑lowering treatment: prospective meta‑analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366(9493), 1267–1278 (2005).
  • Fruchart JC, Sacks F, Hermans MP et al.: The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia. Am. J. Cardiol. 102(Suppl. 10), K1–K34 (2008).
  • Sénécal M, Fodor G, Gagné C et al.: Limitations of statin monotherapy for the treatment of dyslipidemia: a projection based on the Canadian Lipid Study – Observational. Curr. Med. Res. Opin. 25(1), 47–55 (2009).
  • Jacobson TA: Toward ‘pain‑free’ statin prescribing: clinical algorithm for diagnosis and management of myalgia. Mayo Clin. Proc. 83(6), 687–700 (2008).
  • Cicero AFG, Ertek S: Natural sources of antidyslipidaemic agents: is there an evidence‑based approach for their prescription? Med. J. Nutr. Metab. 1(2), 85–93 (2008).
  • Birdsall TC, Kelly GS: Berberine: therapeutic potential of an alkaloid found in several medicinal plants. Altern. Med. Rev. 2, 94–103 (1997).
  • Abidi P, Zhou Y, Jiang JD, Liu J: Extracellular signal regulated kinase‑dependent stabilization of hepatic low density lipoprotein receptor mRNA by herbal medicine berberine. Arterioscler. Thromb. Vasc. Biol. 25(10), 2170–2176 (2005).
  • Lee S, Lim HJ, Park JH et al.: Berberine induced LDLR up‑regulation involves JNK pathway. Biochem. Biophy. Res. Commun. 362(4), 853–857 (2007).
  • Cameron J, Ranheim T, Kulseth MA, Leren TP, Berge KE: Berberine decreases PCSK9 expression in HepG2 cells. Atherosclerosis 201(2), 266–273 (2008).
  • Li H, Chen W, Zhou Y et al.: Identification of mRNA binding proteins that regulate the stability of LDL receptor mRNA through AU‑rich elements. J. Lipid Res. 50, 820–831 (2009).
  • Choi BH, Ahn IS, Kim YH et al.: Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3‑L1 adipocyte. Exp. Mol. Med. 38(6), 599–605 (2006).
  • Brusq JM, Ancellin N, Grondin P et al.: Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine. J. Lipid Res. 47(6), 1281–1288 (2006)
  • Kong W, Wei J, Abidi P et al.: Berberine is a novel cholesterol lowering drug working through a unique mechanism distinct from statins. Nat. Med. 10(12), 1344–1351 (2004).
  • Confirms berberine’s tolerability in patients affected by liver disease, which often limits the prescription of conventional hypocholesterolemic drugs.
  • Cicero AF, Rovati LC, Setnikar I: Eulipidemic effects of berberine administered alone or in combination with other natural cholesterol‑lowering agents. A single‑blind clinical investigation. Arzneimittelforschung 57(1), 26–30 (2007).
  • Kong WJ, Wei J, Zuo ZY et al.: Combination of simvastatin with berberine improves the lipid‑lowering efficacy. Metabolism 57(8), 1029–1037 (2008).
  • Demonstrates the summatory effect of berberine with statin as lipid-lowering agent.
  • Kong WJ, Zhang H, Song DQ et al.: Berberine reduces insulin resistance through protein kinase C‑dependent up‑regulation of insulin receptor expression. Metabolism 58(1), 109–119 (2009).
  • Ko BS, Choi SB, Park SK et al.: Insulin sensitizing and insulinotropic action of berberine from Cortidis rhizoma. Biol. Pharm. Bull. 28(8), 1431–1437 (2005).
  • Zhang W, Xu YC, Guo FJ, Meng Y, Li ML: Antidiabetic effects of cinnamaldehyde and berberine and their impacts on retinol binding protein 4 expression in rats with Type 2 diabetes mellitus. Chin. Med. J. (Eng.) 121(21), 2124–2128 (2008).
  • Yin J, Hu R, Chen M et al.: Effects of berberine on glucose metabolism in vitro. Metabolism 51(11), 1439–1443 (2002).
  • Kim SH, Shin EJ, Kim ED et al.: Berberine activated GLUT‑1‑mediated glucose uptake in 3T3‑L1 adipocytes. Biol. Pharm. Bull. 30(11), 2120–2125 (2007).
  • Yin J, Gao Z, Liu D, Liu Z, Ye J: Berberine improves glucose metabolism through induction of glycolysis. Am. J. Physiol. Endocrinol. Metab. 294(1), E148–E156 (2008).
  • Yi P, Lu FE, Xu LJ, Chen G, Dong H, Wang KF: Berberine reverses free‑fattyacid‑induced insulin resistance in 3T3‑L1 adipocytes through targeting IKKb. World J. Gastroenterol. 14(6), 876–883 (2008).
  • Zhou L, Yang Y, Wang X et al.: Berberine stimulates glucose transport through a mechanism distinct from insulin. Metabolism 56(3), 405–412 (2007).
  • Cheng Z, Pang T, Gu M et al.: Berberine stimulated glucose uptake in L6 myotubes includes both AMPK and p 38 MAPK. Biochim. Biophys. Acta 1760(11), 1682–1689 (2006) .
  • Huang C, Zhang Y, Gong Z et al.: Berberine inhibits 3T3L1 adipocyte differentiation through the PPARg pathway. Biochem. Biophys. Res. Comun. 348(2), 571–578 (2006).
  • Wang SH, Wang WJ, Wang XF, Chen W: Effects of Astragalus polysaccharides and berberine on carbohydrate metabolism and cell differentiation in 3T3‑L1 adipocytes. Zhongguo Zhong Xi Yi Jie He Za Zhi 24(10), 926–928 (2004).
  • Lu SS, Yu YL, Zhu HJ et al.: Berberine promotes glucagons‑like peptide‑1 (7–36 amide) secretion in streptozocin‑induced diabetic rats. J. Endocrinol. 200(2), 159–165 (2009)
  • Zhou J, Zhou S, Tang J et al.: Protective effect of berberine on b cells in streptozotocin‑ and high carbohydrate/ high‑fat‑diet‑induced diabetic rats. Eur. J. Pharmacol. 606(1–3), 262–268 (2009).
  • Pan GY, Wang GJ, Liu XD, Fawcett JP, Xie YY: The involvement of p‑glycoprotein in berberine absorption. Pharmacol. Toxicol. 91(4), 193–197 (2002).
  • Turner N, Li JY, Gosby A et al.: 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), 1414–1418 (2008).
  • Yin J, Zhang H, Ye J: Traditional Chinese medicine in treatment of metabolic syndrome. Endocr. Metab. Immune. Disord. Drug Targets 8(2), 99–111(2008).
  • Wang ZQ, Lu FE, Leng SH et al.: Facilitating effects of berberine on rat pancreatic islets through modulating hepatic nuclear factor 4 a expression and glucokinase activity. World J. Gastroenterol. 14 (39), 6004–6011 (2008).
  • Leng S, Lu F, Xu L: Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion. Acta Pharmacol. Sin. 25(4), 496–502 (2004).
  • Liu WH, Hei ZQ, Nie H et al.: Berberine ameliorates renal injury in streptozocininduced diabetic rats by suppression of both oxidative stress and aldose reductase. Chin. Med. J. 121(8), 706–712 (2008).
  • Very complex and complete study, the first that proposed a new lipid-lowering mechanism of action to explain the biological effects of berberine confirmed by a randomized clinical trial.
  • Zhang Y, Li X, Zou D et al.: Treatment of Type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J. Clin. Endocrinol. Metab. 93(7), 2559–2565 (2008).
  • Yin J, Xing H, Ye J: Efficacy of berberine in patients with Type 2 diabetes mellitus. Metabolism 57(5), 712–717 (2008).
  • Zhao W, Xue R, Zhou ZX, Kong WJ, Jiang JD: Reduction of blood lipid by berberine in hyperlipidemic patients with chronic hepatitis or liver cirrhosis. Biomed. Pharmacother. 62(10), 730–731 (2008).
  • Liu W, Tang F, Deng Y et al.: Berberine reduces fibronectin and collagen accumulation in rat glomerular mesangial cells cultured under high glucose condition. Mol. Cell. Biochem. 325(1–2), 99–105 (2009).
  • Fatehi‑Hassanabad Z, Jafarzadeh M, Tarhini A, Fatehi M: The antihypertensive and vasodilator effects of aqueous extract from Berberis vulgaris fruit on hypertensive rats. Phytother. Res. 19(3), 222–225 (2005).
  • Peychev L: Pharmacological investigation on the cardiovascular effects of Berberine vulgaris on tested animals. Pharmacia 52(1), 118–121 (2005).
  • Chun YT, Yip TT, Lau KL, Kong YC, Sankawa U: A biochemical study on hypotensive effects of berberine in rats. Gen. Pharmacol. 10(3), 177–182 (1979).
  • Wong KK: Mechanism of the aortic relaxation induced by low concentrations of berberine. Planta Med. 64(8), 756–757 (1998).
  • Ko WH, Yao XQ, Lau CW et al.: Vasorelaxant and antiproliferative effects of berberine. Eur. J. Pharmacol. 399(2–3), 187–196 (2000).
  • Kang DG, Sohn EJ, Kwon EK et al.: Effects of berberine on angiotensinconverting enzyme and NO/cGMP system in vessels. Vascul. Pharmacol. 39(6), 281–286 (2002).
  • Olmez E, Ilhan M: Evaluation of the a‑adrenoceptor antagonistic action of berberine in isolated organs. Arzneimittelforschung 42(9), 1095–1097 (1992).
  • Chiou WE, Yen MH, Chen CF: Mechanism of vasodilatory effect of berberine in rat mesenteric artery. Eur. J. Pharmacol. 204(1), 35–40 (1991).
  • Pan LR, Tang Q, Fu Q, Hu BR, Xiang JZ, Qian JQ: Roles of nitric oxide in protective effect of berberine in ethanol‑induced gastric ulcer mice. Acta Pharmacol. Sin. 26(11), 1334–1338 (2005).
  • Liang KW, Yin SC, Ting CT et al.: Berberine inhibits platelet‑derived growth factorinduced growth and migration partly through an AMPK–dependent pathway in vascular smooth muscle cells. Eur. J. Pharmacol. 590(1–3), 343–354 (2008).
  • Liang KW, Ting CT, Yin SC et al.: Berberine suppresses MEK/ERK‑dependent Egr‑1 signalling pathway and inhibits vascular smooth muscle regrowth after in vitro mechanical injury. Biochem. Pharmacol. 71(6), 806–817 (2006).
  • Cho BJ, Im EK, Kwon JH et al.: Berberine inhibits the production of lysophosphatidylcholine‑induced reactive oxygen species and the ERK1,2 pathway in smooth muscle cells. Mol. Cell 20(3), 429–434 (2005).
  • Xu MG, Wang JM, Chen L et al.: Berberineinduced upregulation of endothelial progenitor cells is related to nitric oxide production in healthy subjects. Cardiology 112(4), 279–286 (2008).
  • >Demostrates a direct vascular anti-aging effect of berberine in humans.
  • Xu MG, Wang JM, Chen L, Wang Y, Yang Z, Tao J: Berberine‑induced mobilization of circulating endothelial progenitor cells improves human small artery elasticity. J. Hum. Hypertens. 22(6), 389–393 (2008).
  • Wang JM, Yang Z, Xu MG et al.: Berberine induced decline in circulating CD31+/ CD42‑ microparticles is associated with improvement of endothelial function in humans. Eur. J. Pharmacol. 614(1–3), 77–83 (2009).
  • Hong Y, Hui SS, Chan BT, Hou J: Effect of berberine on catecholamine levels in rats with experimental cardiac hypertrophy. Life Sci. 72(22), 2499–2507 (2003).
  • Hong Y, Hui SC, Chan TY, Hou JY: Effect of berberine on regression of pressure overload induced cardiac hypertrophy in rats. Am. J. Chin. Med. 30(4), 589–599 (2002).
  • Huang WM, Yan H, Jin JM, Yu C, Zhang H: Beneficial effects of berberine on hemodynamics during acute ischemic left ventricular failure in dogs. Chin. Med. J. 105(12), 1014–1019 (1992).
  • Wang YX, Zheng YM, Zhou XB: Inhibitory effects of berberine on ATP‑sensitive K+ channels in cardiac myocytes. Eur. J. Pharmacol. 316(2–3), 307–315 (1996).
  • Marin‑Neto JA, Maciel BC, Secches AL, Gallo L Jr: Cardiovascular effects of berberine in patients with severe congestive heart failure. Clin. Cardiol. 11(4), 253–260 (1988).
  • First clinical test of berberine in heart failure.
  • Zeng XH, Zeng XJ, Li YY: Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am. J. Cardiol. 92(2), 173–176 (2003).
  • Lau CW, Yao XQ, Chen ZY, Ko WH, Huang Y: Cardiovascular actions of berberine. Cardiovasc. Drug Rev. 19(3), 234–244 (2001).
  • Huang CG, Chu ZL, Wei SJ, Jiang H, Jiao BH: Effects of berberine on arachidonic acid metabolism in rabbit platelets and endothelial cells. Thromb. Res. 106(4–5), 223–227 (2002).
  • Huang CG, Chu ZL, Yang ZM: The progress in pharmacological researches on berberine. Comun. Inform. Pharm. 9(4), 10–12 (1991).
  • Holy EW, Akhmedov A, Lüscher TF, Tanner FC: Berberine a natural lipid‑lowering drug, exerts prothrombic effects on vascular cells. J. Mol. Cell. Cardiol. 46(2), 234–240 (2009).
  • Guo Y, Wang QZ, Li FM, Jiang X, Zuo YF, Wang L: Biochemical pathways in the antiatherosclerotic effect of berberine. Chin. Med. J. (Eng.) 121(13), 1197–1203 (2008).
  • Pandey MK, Sung B, Kunnumakkara AB et al.: Berberine modifies cysteine 179 of IkBa kinase, suppresses nuclear factor‑k‑Bregulated antiapoptotic gene products, and potentiates apoptosis. Cancer Res. 68(13), 5370–5379 (2008).
  • Hwang JM, Wang CJ, Chou FP et al.: Inhibitory effect of berberine on tert‑butylhydroperoxide‑induced oxidative damage in rat liver. Arch. Toxicol. 76(11), 664–670 (2002).
  • Li BX, Zhang MS, Bao LH: Study of pharmacokinetics of berberine after oral administration in human being. J. Haerbin Med. Univ. 29, 382–385 (1995)
  • Yuan J, Shen XZ, Zhu XS: Effect of berberine on transit time of human small intestine. Zhongguo Zhong Xi Yi Jie He Za Zhi 14(12), 718–720 (1994).
  • Imanshahidi M, Hosseinzadeh H: Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother. Res. 22(8), 999–1012 (2008).
  • Hu YJ, Liu Y, Xiao XH: Investigation of the interaction between berberine and human serum albumin. Biomacromolecules DOI: 10.1021/bm801120k (2009) (Epub ahead of print).
  • Tan YZ, Wu AC, Tan BY et al.: Study on the interactions of berberine displace other drug from their plasma proteins binding sites. Chin. Pharmacol. Bull. 18, 576–578 (2002).
  • Chan E: Displacement of bilirubin from albumin by berberine. Biol. Neonat. 63(4), 201–208 (1993).
  • Tsai PL, Tsai TH: Hepatobiliary excretion of berberine. Drug. Metab. Dispos. 32(4), 405–412 (2003).
  • Zuo F, Nakamura N, Akao T, Hattori M: Pharmacokinetics of berberine and its main metabolites in conventional and pseudo germ‑free rats determined by liquid chromatography/ion trap mass spectrometry. Drug Metab. Dispos. 34(12), 2064–2072 (2006).
  • Chen CM, Chang HC: Determination of berberine in plasma, urine and bile by high performance liquid chromatography. J. Chromatogr. 665(1), 117–123 (1995).
  • Pan JF, Yu C, Zhu DY et al.: Identification of three sulfate‑conjugated metabolites of berberine chloride in healthy volunteers’ urine after oral administration. Acta Pharmacol. Sin. 23(1), 77–82 (2002).
  • Raner GM, Cornelius S, Moulick K et al.: Effects of herbal products on human cytochrome P450(2E1) activity. Food Chem. Tox. 45(12), 2359–2365 (2007).
  • Zhao X, Zhang JJ, Wang X, Bu XY, Lou YQ, Zhang GL: Effect of berberine on hepatocyte proliferation inducible nitric oxide synthase expression, cyrochrome 450 2E1 and 1A2 activities in diethylnitrosamine‑ and phenobarbital‑treated rats. Biomed. Pharmacother. 62(9), 567–572 (2008).
  • Xin HW, Wu XC, Li Q et al.: The effects of berberine on the pharmacokinetics of cyclosporine A in healthy volunteers. Methods Find. Exp. Clin. Pharmacol. 28(1), 25–29 (2006).
  • Wu X, Li Q, Xin H, Yu A, Zhong M: Effects of berberine on the blood concentration of cyclosporine A in renal transplanted recipients: clinical and pharmacokinetic study. Eur. J. Clin. Pharmacol. 61(8), 567–572 (2005).
  • Vrzal R, Zdarilova A, Ulrichova J et al.: Activation of the aryl hydrocarbon receptor by berberine in HepG2 and H4IIEcells: biphasic effect on CYP1A1. Biochem. Pharmacol. 70(6), 925–936 (2005).
  • Lin HL, Liu TY, Wu CW, Chi CW: Berberine modulates expression of mdr1 gene product and the responses of the digestive tract cancers to Paclitaxel. Br. J. Cancer. 81(3), 416–422 (1999).
  • Sabir M, Bhide NK: Study of some pharmacological actions of berberine. Indian J. Physiol. Pharmacol. 15(3), 111–132 (1971).
  • Pasqual MS, Lauer CP, Moyna P, Henriques JA: Genotoxicity of the isoquinoline alkaloid berberine in prokaryotic and eukaryotic organisms. Mutat. Res. 286(2), 243–252 (1993).
  • Grycova L, Dostal J, Marek R: Quarternary protoberberine alkaloids. Phytochemistry 68(2), 150–175 (2007).
  • Holy EW, Akhmedov A, Lüscher TF, Tanner FC: Berberine, a natural lipidlowering drug, exerts prothrombotic effects on vascular cells. J. Mol. Cell. Cardiol. 46(2), 234–240 (2009).
  • Chu ZL, Huang CG, Xu ZP. The anti‑platelet effect of berberine and its mechanism. Zhongguo Zhong Xi Yi Jie He Za Zhi 14(8), 510–512 (1994).

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