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Berberine and Its Role in Chronic Disease

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Anti-inflammatory Nutraceuticals and Chronic Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 928))

Abstract

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 [2] (Amur corktree), Coptis chinensis (Chinese goldthread), Tinospora cordifolia, Argemone mexicana (prickly poppy) and Eschscholzia californica (Californian poppy). In vitro it exerts significant anti-inflammatory and antioxidant activities. In animal models berberine has neuroprotective and cardiovascular protective effects. In humans, its lipid-lowering and insulin-resistance improving actions have clearly been demonstrated in numerous randomized clinical trials. Moreover, preliminary clinical evidence suggest the ability of berberine to reduce endothelial inflammation improving vascular health, even in patients already affected by cardiovascular diseases. Altogether the available evidences suggest a possible application of berberine use in the management of chronic cardiometabolic disorders.

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References

  1. Banegas JR, López-García E, Dallongeville J et al (2011) Achievement of treatment goals for primary prevention of cardiovascular disease in clinical practice across Europe: the EURIKA study. Eur Heart J 32:2143–2152

    Article  PubMed  PubMed Central  Google Scholar 

  2. Saha S, Gerdtham UG, Johansson P (2010) Economic evaluation of lifestyle interventions for preventing diabetes and cardiovascular diseases. Int J Environ Res Public Health 7:3150–3195

    Article  PubMed  PubMed Central  Google Scholar 

  3. King DE, Mainous AG, Matheson EM, Everett CJ (2013) Impact of healthy lifestyle on mortality in people with normal blood pressure, LDL cholesterol, and C-reactive protein. Eur J Cardiovasc Prev Rehabil 20(1):73–79

    Article  Google Scholar 

  4. Cicero AF, Derosa G, D’angelo A et al (2009) Gender-specific haemodynamic and metabolic effects of a sequential training programme on overweight-obese hypertensives. Blood Press 18:111–116

    Article  CAS  PubMed  Google Scholar 

  5. Cicero AF, Ertek S (2008) Natural sources of antidyslipidaemic agents: is there an evidence-based approach for their prescription? Med J Nutr Metab 2:85–93

    Article  Google Scholar 

  6. NCEP Expert Panel (2001) Expert Panel on detection, evaluation and treatment of high blood cholesterol in adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) (Adult Treatment Panel III). J Am Med Assoc 285:2486–2497

    Article  Google Scholar 

  7. Catapano AL, Reiner Z, De Backer G et al (2011) European Society of Cardiology (ESC); European Atherosclerosis Society (EAS). ESC/EAS Guidelines for the management of dyslipidaemias The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis 217:3–46

    Article  CAS  PubMed  Google Scholar 

  8. Hasani-Ranjbar S, Nayebi N, Moradi L et al (2010) The efficacy and safety of herbal medicines used in the treatment of hyperlipidemia: a systematic review. Curr Pharm Res 16:2935–2947

    Article  CAS  Google Scholar 

  9. McGowan MP, Proulx S (2009) Nutritional supplements and serum lipids: does anything work? Curr Atheroscler Rep 11:470–476

    Article  CAS  PubMed  Google Scholar 

  10. Kim JY, Kwon O (2011) Culinary plants and their potential impact on metabolic overload. Ann NY Acad Sci 1229:133–139

    Article  CAS  PubMed  Google Scholar 

  11. Xia X, Weng J (2010) Targeting metabolic syndrome: candidate natural agents. J Diabetes 2:243–249

    Article  CAS  PubMed  Google Scholar 

  12. Birdsall TC, Kelly GS (1997) Berberine: therapeutic potential of an alkaloid found in several medicinal plants. Altern Med Rev 2:94–103

    Google Scholar 

  13. Vuddanda PR, Chakraborty S, Singh S (2010) Berberine: a potential phytochemical with multispectrum therapeutic activities. Expert Opin Investig Drugs 19:1297–1307

    Article  CAS  PubMed  Google Scholar 

  14. Souri E, Dehmobed-Sharifabadi A, Nazifia A, Farsam H (2004) Antioxidant activity of sixty plants from Iran. Iran J Pharm Res 13:55–59

    Google Scholar 

  15. Chevallier A (2001) The encyclopedia of medicinal plants. Dorling Kindersley, St Leonards, pp 234–237

    Google Scholar 

  16. Timothy CBN, Gregory S, Kelly ND (1997) Berberine: therapeutic potential of an alkaloid found in several medicinal plants. Altern Med Rev 13:94–103

    Google Scholar 

  17. Kunwar RM, Nepal BK, Kshhetri HB et al (2006) Ethnomedicine in Himalaya: a case study from Dolpa, Humla, Jumla and Mustang districts of Nepal. J Ethnobiol Ethnomed 13:27

    Article  Google Scholar 

  18. Fatehi-Hassanabad Z, Jafarzadeh M, Tarhini A, Fatehi M (2005) The antihypertensive and vasodilator effects of aqueous extract from Berberis vulgaris fruit on hypertensive rats. Phytother Res 13(3):222–225

    Article  Google Scholar 

  19. Ivanovska N, Philipov S (1996) Study on the anti-inflammatory action of Berberis vulgaris root extract, alkaloid fractions and pure alkaloids. Int J Immunopharmacol 13(10):553–561

    Article  Google Scholar 

  20. Imanshahidi M, Hosseinzadeh H (2008) Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, Berberine. Phytother Res 13:999–1012

    Article  CAS  Google Scholar 

  21. Mills S, Bone K (2000) Principals and practice of phytotherapy. Churchill Livingstone, Edinburgh, pp 338–341

    Google Scholar 

  22. Bone K (2003) A clinical guide to blending liquid herbs: herbal formulations for the individual patient. Churchill Livingstone, St Louis, pp 422–429

    Google Scholar 

  23. Khosrokhavar R, Ahmadiani AS (2010) Antihistaminic and anticholinergic activity of methanolic extract of barberry fruit (Berberis vulgaris) in the Guinea-Pig Ileum. J Med Plants 13:99–105

    Google Scholar 

  24. Akhter MH, Sabir M, Bhide NK (1979) Possible mechanism of antidiarrheal effect of berberine. Indian J Med Res 13:233–241

    Google Scholar 

  25. Rabbani GHBT, Knight J, Sanyal SC, Alam K (1987) Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholera. J Infect Dis 13:979–984

    Article  Google Scholar 

  26. Amin AH, Subbaiah TV, Abbasi KM (1969) Berberine sulfate: antimidrobial activity, bioassay, and mode of action. Can J Microbiol 13:1067–1076

    Article  Google Scholar 

  27. Sabir M (1971) Study of some pharmacological actions of berberine. Indian J Physiol Pharmacol 13:111–132

    Google Scholar 

  28. Pan GY, Wang GJ, Liu XD, Fawcett JP, Xie YY (2002) The involvement of P-glycoprotein in berberine absorption. Pharmacol Toxicol 91:193–197

    Article  CAS  PubMed  Google Scholar 

  29. Tsai PL, Tsai TH (2003) Hepatobiliary excretion of berberine. Drug Metab Dispos 32:405–412

    Article  Google Scholar 

  30. Zuo F, Nakamura N, Akao T, Hattori M (2006) 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 34:2064–2072

    Article  CAS  PubMed  Google Scholar 

  31. Chen CM, Chang HC (1995) Determination of berberine in plasma, urine and bile by high performance liquid chromatograpy. J Chromatogr 665:117–123

    Article  CAS  Google Scholar 

  32. Raner GM, Cornelious S, Moulick K et al (2007) Effects of herbal products on human cytochrome P450(2E1) activity. Food Chem Tox 45:2359–2365

    Article  CAS  Google Scholar 

  33. Zhao X, Zhang JJ, Wang X et al (2008) Effect of berberine on hepatocyte proliferation inducible nitric oxide synthase expression, cytochrome 450 2E1 and 1A2 activities in diethylnitrosamine- and Phenobarbital-treated rats. Biomed Pharmacother 62:567–572

    Article  CAS  PubMed  Google Scholar 

  34. Furukawa S, Fujita T, Shimabukuro M et al (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Investig 114(12):1752–1761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bonnefont-Rousselot D (2002) Glucose and reactive oxygen species. Curr Opin Clin Nutr Metab Care 5(5):561–568

    Article  CAS  PubMed  Google Scholar 

  36. Alberici LC, Vercesi AE, Oliveira HC (2011) Mitochondrial energy metabolism and redox responses to hypertriglyceridemia. J Bioenerg Biomembr 43(1):19–23

    Article  CAS  PubMed  Google Scholar 

  37. Rösen P, Nawroth PP, King G et al (2001) The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a congress series sponsored by UNESCO-MCBN, the American diabetes association and the German diabetes society. Diab Metab Res Rev 17(3):189–212

    Article  Google Scholar 

  38. Evans JL, Goldfine ID, Maddux BA, Grodsky GM (2003) Are oxidative stress—activated signaling pathways mediators of insulin resistance and β-cell dysfunction? Diabetes 52(1):1–8

    Article  CAS  PubMed  Google Scholar 

  39. Kaneto H, Xu G, Fujii N, Bonner-Weir S, Weir GC (2002) Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression. J Biol Chem 277(33):30010–30018

    Article  CAS  PubMed  Google Scholar 

  40. Scivittaro V, Ganz MB, Weiss MF (2000) AGEs induce oxidative stress and activate protein kinase C-β(II) in neonatal mesangial cells. Am J Physiol 278(4):F676–F683

    CAS  Google Scholar 

  41. Goldin A, Beckman JA, Schmidt AM, Creager MA (2006) Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 114(6):597–605

    Article  CAS  PubMed  Google Scholar 

  42. Frey RS, Ushio-Fukai M, Malik AB (2009) NADPH oxidase-dependent signaling in endothelial cells role in physiology and pathophysiology. Antioxid Redox Signal 11:791–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Furukawa S, Fujita T, Shimabukuro M et al (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Investig 114:1752–1761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Maiese K (2015) New insights for oxidative stress and diabetes mellitus. Oxid Med Cell Longev 2015:875961

    Article  PubMed  PubMed Central  Google Scholar 

  45. Wu XD, Liu WL, Zeng K et al (2014) Advanced glycation end products activate the miRNA/RhoA/ROCK2 pathway in endothelial cells. Microcirculation 21(2):178–186

    Article  CAS  PubMed  Google Scholar 

  46. Cheng F, Wang Y, Li J et al (2013) Berberine improves endothelial function by reducing endothelial microparticles-mediated oxidative stress in humans. Int J Cardiol 167:936–942

    Article  PubMed  Google Scholar 

  47. 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 88:369–378

    Article  CAS  PubMed  Google Scholar 

  48. Hsieh S, Kuo WH, Lin TW et al (2007) Protective effects of berberine against low-density lipoprotein (LDL) oxidation and oxidized LDL-induced cytotoxicity on endothelial cells. J Agric Food Chem 55:10437–10445

    Article  CAS  PubMed  Google Scholar 

  49. Kim JE, Kim YW, Lee IK et al (2008) AMP-activated protein kinase activation by 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) inhibits palmitate-induced endothelial cell apoptosis through reactive oxygen species suppression. J Pharmacol Sci 106:394–403

    Article  CAS  PubMed  Google Scholar 

  50. Wang S, Zhang M, Liang B et al (2010) AMPKα2 deletion causes aberrant expression and activation of NAD(P)H oxidase and consequent endothelial dysfunction in vivo: role of 26S proteasomes. Circ Res 106:1117–1128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ceolotto G, Gallo A, Papparella I et al (2007) Rosiglitazone reduces glucose-induced oxidative stress mediated by NAD(P)H oxidase via AMPK-dependent mechanism. Arterioscler Thromb Vasc Biol 27:2627–2633

    Article  CAS  PubMed  Google Scholar 

  52. Lee KH, Lo HL, Tang WC et al (2014) A gene expression signature-based approach reveals the mechanisms of action of the Chinese herbal medicine berberine. Sci Rep 4:6394

    Article  CAS  PubMed  Google Scholar 

  53. Turner N, Li JY, Gosby A, To SW, Cheng Z, Miyoshi H et al (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):1414–1418

    Article  CAS  PubMed  Google Scholar 

  54. Li Z, Geng YN, Jiang JD, Kong WJ (2014) Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus. Evid Based Complement Alternat Med 2014:289264

    PubMed  PubMed Central  Google Scholar 

  55. Morrow VA, Foufelle F, Connell JM et al (2003) Direct activation of AMP-activated protein kinase stimulates nitric-oxide synthesis in human aortic endothelial cells. J Biol Chem 278:31629–31639

    Article  CAS  PubMed  Google Scholar 

  56. Zhang ZM, Jiang B, Zheng XX (2005) Effect of l-tetrahydropalmatine on expression of adhesion molecules induced by lipopolysaccharides in human umbilical vein endothelium cell. Zhongguo Zhong Yao Za Zhi 30(11):861–864

    CAS  PubMed  Google Scholar 

  57. Wang Y, Huang Y, Lam KS et al (2009) Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase. Cardiovasc Res 82(3):484–492

    Article  CAS  PubMed  Google Scholar 

  58. Kukidome D, Nishikawa T, Sonoda K et al (2006) Activation of AMP-activated protein kinase reduces hyperglycemia-induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells. Diabetes 55:120–127

    Article  CAS  PubMed  Google Scholar 

  59. Xie Z, Zhang J, Wu J, Viollet B, Zou MH (2008) Upregulation of mitochondrial uncoupling protein-2 by the AMP-activated protein kinase in endothelial cells attenuates oxidative stress in diabetes. Diabetes 57(12):3222–3230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Chatuphonprasert W, Lao-ong T, Jarukamjorn K (2013) Improvement of superoxide dismutase and catalase in streptozotocin-nicotinamide-induced type 2-diabetes in mice by berberine and glibenclamide. Pharm Biol (Epub ahead of print). doi:10.3109/13880209.2013.839714

    Google Scholar 

  61. Lao-ong T, Chatuphonprasert W, Nemoto N, Jarukamjorn K (2012) Alteration of hepatic glutathione peroxidase and superoxide dismutase expression in streptozotocin-induced diabetic mice by berberine. Pharm Biol 50(8):1007–1012

    Article  CAS  PubMed  Google Scholar 

  62. Ceballos-Picot I, Witko-Sarsat V, Merad-Boudia M et al (1996) Glutathione antioxidant system as a marker of oxidative stress in chronic renal failure. Free Radic Biol Med 21:845–853

    Article  CAS  PubMed  Google Scholar 

  63. Abd El-Wahab AE, Ghareeb DA, Sarhan EE et al (2013) In vitro biological assessment of Berberis vulgaris and its active constituent, berberine: antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effects. BMC Complement Altern Med 13:218

    Article  PubMed  PubMed Central  Google Scholar 

  64. Hsu YY, Chen CS, Wu SN, Jong YJ, Lo YC (2012) Berberine activates Nrf2 nuclear translocation and protects against oxidative damage via a phosphatidylinositol 3-kinase/Akt-dependent mechanism in NSC34 motor neuron-like cells. Eur J Pharm Sci 46:415–425

    Article  CAS  PubMed  Google Scholar 

  65. Mo C, Wang L, Zhang J et al (2014) The crosstalk between Nrf2 and AMPK signal pathways is important for the anti-inflammatory effect of berberine in LPS-stimulated macrophages and endotoxin-shocked mice. Antioxid Redox Signal 20(4):574–588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Hsu YY, Tseng YT, Lo YC (2013) Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth. Toxicol Appl Pharmacol 272(3):787–796

    Article  CAS  PubMed  Google Scholar 

  67. Bae J, Lee D, Kim YK et al (2013) Berberine protects 6-hydroxydopamine-induced human dopaminergic neuronal cell death through the induction of heme oxygenase-1. Mol Cells 35(2):151–157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Vomhof-Dekrey EE, PickloSr MJ (2012) The Nrf2-antioxidant response element pathway: a target for regulating energy metabolism. J Nutr Biochem 23(10):1201–1206

    Article  CAS  PubMed  Google Scholar 

  69. Xie X, Chang X, Chen L et al (2013) Berberine ameliorates experimental diabetes-induced renal inflammation and fibronectin by inhibiting the activation of RhoA/ROCK signaling. Mol Cell Endocrinol 381(1–2):56–65

    Article  CAS  PubMed  Google Scholar 

  70. Choi B-H, Ahn I-S, Kim Y-H et al (2006) Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte. ExpMol Med 38(6):599–605

    CAS  Google Scholar 

  71. Lou T, Zhang Z, Xi Z et al (2011) Berberine inhibits inflammatory response and ameliorates insulin resistance in hepatocytes. Inflammation 34(6):659–667

    Article  CAS  PubMed  Google Scholar 

  72. Jeong HW, Hsu KC, Lee JW et al (2009) Berberine suppresses proinflammatory responses through AMPK activation in macrophages. Am J Physiol Endocrinol Metab 296(4):E955–E964

    Article  CAS  PubMed  Google Scholar 

  73. Lin W-C, Lin JY (2011) Five bitter compounds display different anti-inflammatory effects through modulating cytokine secretion using mouse primary splenocytes in vitro. J Agric Food Chem 59(1):184–192

    Article  CAS  PubMed  Google Scholar 

  74. Shang W, Liu J, Yu X, Zhao J (2010) Effects of berberine on serum levels of inflammatory factors and inflammatory signaling pathway in obese mice induced by high fat diet. Zhongguo Zhong Yao Za Zhi 35(11):1474–1477

    CAS  PubMed  Google Scholar 

  75. Chen Y, Wang Y, Zhang J, Sun C, Lopez A (2011) Berberine improves glucose homeostasis in streptozotocin-induced diabetic rats in association with multiple factors of insulin resistance. ISRN Endocrinol 2011:519371

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Xing L-J, Zhang L, Liu T (2011) Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease (NAFLD) rat liver. Eur J Pharmacol 668(3):467–471

    Article  CAS  PubMed  Google Scholar 

  77. Cui G, Qin X, Zhang Y et al (2009) Berberine differentially modulates the activities of ERK, p 38 MAPK, and JNK to suppress Th17 and Th1 T cell differentiation in type 1 diabetic mice. J Biol Chem 284(41):28420–28429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Chueh WH, Lin JY (2012) Protective effect of isoquinoline alkaloid berberine on spontaneous inflammation in the spleen, liver and kidney of non-obese diabetic mice through downregulating gene expression ratios of pro-/anti-inflammatory and Th1/Th2 cytokines. Food Chem 131(4):1263–1271

    Article  CAS  Google Scholar 

  79. Zhang Y, Li X, Zou D et al (2008) Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab 93(7):2559–2565

    Article  CAS  PubMed  Google Scholar 

  80. Meng S, Wang LS, Huang ZQ et al (2012) Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention. Clin Exp Pharmacol Physiol 39(5):406–411

    Article  CAS  PubMed  Google Scholar 

  81. Dubois RN, Abramson SB, Crofford L (1998) Cyclooxygenase in biology and disease. FASEB J 12(12):1063–1073

    CAS  PubMed  Google Scholar 

  82. Mima A (2013) Inflammation and oxidative stress in diabetic nephropathy: new insights on its inhibition as new therapeutic targets. J Diab Res 2013:248563

    Google Scholar 

  83. Lee D, Bae J, Kim YK et al (2013) Inhibitory effects of berberine on lipopolysaccharide-induced inducible nitric oxide synthase and the high-mobility group box 1 release in macrophages. Biochem Biophys Res Commun 431(3):506–511

    Article  CAS  PubMed  Google Scholar 

  84. Zhou Y, Liu SQ, Yu L et al (2015) Berberine prevents nitric oxide-induced rat chondrocyte apoptosis and cartilage degeneration in a rat osteoarthritis model via AMPK and p38 MAPK signaling. Apoptosis 20(9):1187–1199

    Article  CAS  PubMed  Google Scholar 

  85. Gratas-Delamarche A, Derbré F, Vincent S, Cillard J (2014) Physical inactivity, insulin resistance, and the oxidative-inflammatory loop. Free Rad Res 48(1):93–108

    Article  CAS  Google Scholar 

  86. Solinas G, Karin M (2010) JNK1 and IKKbeta: molecular links between obesity and metabolic dysfunction. FASEB J 24(8):2596–2611

    Article  CAS  PubMed  Google Scholar 

  87. Karin M (1999) Positive and negative regulation of IκB kinase activity through IKKβ subunit phosphorylation. Science 284(5412):309–313

    Article  PubMed  Google Scholar 

  88. Yi P, Lu FE, Xu LJ et al (2008) Berberine reverses free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ. World J Gastroenterol 14(6):876–883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Pandey MK, Sung B, Kunnumakkara AB et al (2008) Berberine modifies cysteine 179 of IκBα kinase, suppresses nuclear factor-κB-regulated antiapoptotic gene products, and potentiates apoptosis. Cancer Res 68(13):5370–5379

    Article  CAS  PubMed  Google Scholar 

  90. Shi J, Wei L (2013) Rho kinases in cardiovascular physiology and pathophysiology: the effect of fasudil. J Cardiovasc Pharmacol 62(4):341–354

    Article  CAS  PubMed  Google Scholar 

  91. Xie X, Peng J, Chang X et al (2013) Activation of RhoA/ROCK regulates NF-κB signaling pathway in experimental diabetic nephropathy. Mol Cell Endocrinol 369(1–2):86–97

    Article  CAS  PubMed  Google Scholar 

  92. Remppis A, Bea F, Greten HJ et al (2010) Rhizoma Coptidis inhibits LPS-induced MCP-1/CCL2 production in murine macrophages via an AP-1 and NFκB-dependent pathway. Mediat Inflamm 2010:194896

    Article  CAS  Google Scholar 

  93. Kuo CL, Chi CW, Liu TY (2004) The anti-inflammatory potential of berberine in vitro and in vivo. Cancer Lett 203(2):127–137

    Article  CAS  PubMed  Google Scholar 

  94. Schonthaler HB, Guinea-Viniegra J, Wagner EF (2011) Targeting inflammation by modulating the Jun/AP-1 pathway. Ann Rheum Dis 70(1):i109–i112

    Article  CAS  PubMed  Google Scholar 

  95. Ricote M, Li AC, Willson TM et al (1998) The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation. Nature 391(6662):79–82

    Article  CAS  PubMed  Google Scholar 

  96. Delerive P, Martin-Nizard F, Chinetti G et al (1999) Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway. Circ Res 85(5):394–402

    Article  CAS  PubMed  Google Scholar 

  97. Pasceri V, Wu HD, Willerson JT, Yeh ETH (2000) Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-γ activators. Circulation 101(3):235–238

    Article  CAS  PubMed  Google Scholar 

  98. Chen FL, Yang ZH, Liu Y et al (2008) Berberine inhibits the expression of TNFα, MCP-1, and IL-6 in AcLDL-stimulated macrophages through PPARγ pathway. Endocrine 33(3):331–337

    Article  CAS  PubMed  Google Scholar 

  99. Feng AW, Gao W, Zhou GR et al (2012) Berberine ameliorates COX-2 expression in rat small intestinal mucosa partially through PPARγ pathway during acute endotoxemia. Int Immunopharmacol 12(1):182–188

    Article  CAS  PubMed  Google Scholar 

  100. Krook A, Wallberg-Henriksson H, Zierath JR (2004) Sending the signal: molecular mechanisms regulating glucose uptake. Med Sci Sports Exerc 36:1212–1217

    Article  CAS  PubMed  Google Scholar 

  101. Kim SH, Shin EJ, Kim ED (2007) Berberine activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes. Biol Pharm Bull 30:2120–2125

    Article  CAS  PubMed  Google Scholar 

  102. Pan GY, Huang ZJ, Wang GJ et al (2003) The antihyperglycaemic activity of berberine arises from a decrease of glucose absorption. Planta Med 69:632–636

    Article  CAS  PubMed  Google Scholar 

  103. Shetty M, Loeb JN, Vikstrom K, Ismail-Beigi F (1993) Rapid activation of GLUT-1 glucose transporter following inhibition of oxidative phosphorylation in clone 9 cells. J Biol Chem 268:17225–17232

    CAS  PubMed  Google Scholar 

  104. Rubin D, Ismail-Beigi F (2003) Distribution of Glut1 in detergent-resistant membranes (DRMs) and non-DRM domains: effect of treatment with azide. Am J Physiol Cell Physiol 285:C377–C383

    Article  CAS  PubMed  Google Scholar 

  105. Barnes K, Ingram JC, Porras OH et al (2002) Activation of GLUT1 by metabolic and osmotic stress: potential involvement of AMP-activated protein kinase (AMPK). J Cell Sci 115:2433–2442

    CAS  PubMed  Google Scholar 

  106. Barros LF, Barnes K, Ingram JC et al (2001) Hyperosmotic shock induces both activation and translocation of glucose transporters in mammalian cells. Pflugers Arch 442:614–621

    Article  CAS  PubMed  Google Scholar 

  107. Louters LL, Dyste SG, Frieswyk D et al (2006) Methylene blue stimulates 2-deoxyglucose uptake in L929 fibroblast cells. Life Sci 78:586–591

    Article  CAS  PubMed  Google Scholar 

  108. Kumar A, Xiao YP, Laipis PJ (2004) Glucose deprivation enhances targeting of GLUT1 to lipid rafts in 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab 286:E568–E576

    Article  CAS  PubMed  Google Scholar 

  109. Roelofs B, Tidball A, Lindborg AE et al (2006) Acute activation of glucose uptake by glucose deprivation in L929 fibroblast cells. Biochimie 88:1941–1946

    Article  CAS  PubMed  Google Scholar 

  110. Jing M, Ismail-Beigi F (2007) Critical role of 5′-AMP-activated protein kinase in the stimulation of glucose transport in response to inhibition of oxidative phosphorylation. Am J Physiol Cell Physiol 292:C477–C487

    Article  CAS  PubMed  Google Scholar 

  111. Jing M, Cheruvu VK, Ismail-Beigi F (2008) Stimulation of glucose transport in response to activation of distinct AMPK signaling pathways. Am J Physiol Cell Physiol 295:C1071–C1082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Meyer JA, Froelich JM, Reid GE, Karunarathne WK, Spence DM (2008) Metal-activated C-peptide facilitates glucose clearance and the release of a nitric oxide stimulus via the GLUT1 transporter. Diabetologia 51:175–182

    Article  CAS  PubMed  Google Scholar 

  113. Kong WJ, Zhang H, Song DQ et al (2009) Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. Metabolism 58:109–119

    Article  CAS  PubMed  Google Scholar 

  114. Ko BS, Choi SB, Park SK et al (2005) Insulin sensitizing and insulin otropic action of berberine from Cortidis rhizoma. Biol Pharm Bull 28:1431–1437

    Article  CAS  PubMed  Google Scholar 

  115. Zhang W, Xu YC, Guo FJ, Meng Y, Li ML (2008) Antidiabetic effects of cinnamaldehyde and berberine and their impacts on retinol binding protein 4 expression in rats with type 2 diabetes mellitus. Chin Med J121:2124–2128

    Google Scholar 

  116. Ni WJ, Ding HH, Tang LQ (2015) Berberine as a promising anti-diabetic nephropathy drug: An analysis of its effects and mechanisms. Eur J Pharmacol 760:103–112

    Article  CAS  PubMed  Google Scholar 

  117. Yin J, Gao Z, Liu D, Liu Z, Ye J (2008) Berberine improves glucose metabolism through induction of glycolysis. Am J Physiol Endocrinol Metab 294:E148–E156

    Article  CAS  PubMed  Google Scholar 

  118. Chang W, Zhang M, Li J et al (2013) Berberine improves insulin resistance in cardiomyocytes via activation of 5′-adenosine monophosphate-activated protein kinase. Metabolism 62(8):1159–1167

    Article  CAS  PubMed  Google Scholar 

  119. Liu LZ, Cheung SC, Lan LL et al (2010) Berberine modulates insulin signaling transduction in insulin-resistant cells. Mol Cell Endocrinol 317(1–2):148–153

    Article  CAS  PubMed  Google Scholar 

  120. Zhang H, Wei J, Xue R et al (2010) Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism 59(2):285–292

    Article  PubMed  CAS  Google Scholar 

  121. Dong H, Wang N, Zhao L, Lu F (2012) Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evidence-Based Complement Altern Med 2012:591654

    Article  Google Scholar 

  122. Dong H, Zhao Y, Zhao L, Lu F (2013) The effects of berberine on blood lipids: a systemic review and meta-analysis of randomized controlled trials. Planta Med 79(6):437–446

    Article  CAS  PubMed  Google Scholar 

  123. Cicero AF, Tartagni E, Ertek S (2014) Nutraceuticals for metabolic syndrome management: from laboratory to benchside. Curr Vasc Pharmacol 12:565–571

    Article  CAS  PubMed  Google Scholar 

  124. Cianci A, Cicero AF, Colacurci N, Matarazzo MG, De Leo V (2012) Activity of isoflavones and berberine on vasomotor symptoms and lipid profile in menopausal women. Gynecol Endocrinol 28:699–702

    Article  CAS  PubMed  Google Scholar 

  125. Dong B, Li H, Singh AB, Cao A, Liu J (2015) Inhibition of PCSK9 transcription by berberine involves down-regulation of hepatic HNF1α protein expression through the ubiquitin-proteasome degradation pathway. J Biol Chem 290(7):4047–4058

    Article  CAS  PubMed  Google Scholar 

  126. Kong W, Wei J, Abidi P et al (2004) Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med 10:1344–1351

    Article  CAS  PubMed  Google Scholar 

  127. Lubrano V, Balzan S (2014) LOX-1 and ROS, inseparable factors in the process of endothelial damage. Free Radic Res 48:841–848

    Article  CAS  PubMed  Google Scholar 

  128. Kong WJ, Liu J, Jiang JD (2006) Human low-density lipoprotein receptor gene and its regulation 4. J Mol Med 84:29–36

    Article  CAS  PubMed  Google Scholar 

  129. Cominacini L, Anselmi M, Garbin U et al (2005) Enhanced plasma levels of oxidized low-density lipoprotein increase circulating nuclear factor-kappa B activation in patients with unstable angina. J Am Coll Cardiol 46:799–806

    Article  CAS  PubMed  Google Scholar 

  130. Pirillo A, Catapano AL (2013) Soluble lectin-like oxidized low density lipoprotein receptor-1 as a biochemical marker for atherosclerosis-related diseases. Dis Markers 35:413–418

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Guan S, Wang B, Li W, Guan J, Fang X (2010) Effects of berberine on expression of LOX-1 and SR-BI in human macrophage-derived foam cells induced by ox-LDL. Am J Chin Med 38:1161–1169

    Article  CAS  PubMed  Google Scholar 

  132. Huang Z, Dong F, Li S et al (2012) Berberine-induced inhibition of adipocyte enhancer-binding protein 1 attenuates oxidized low-density lipoprotein accumulation and foam cell formation in phorbol 12-myristate 13-acetate-induced macrophages. Eur J Pharmacol 690(1–3):164–169

    Article  CAS  PubMed  Google Scholar 

  133. Chi L, Peng L, Pan N, Hu X, Zhang Y (2014) The anti-atherogenic effects of berberine on foam cell formation are mediated through the upregulation of sirtuin 1. Int J Mol Med 34(4):1087–1093

    CAS  PubMed  Google Scholar 

  134. Chi L, Peng L, Hu X, Pan N, Zhang Y (2014) Berberine combined with atorvastatin downregulates LOX-1 expression through the ET-1 receptor in monocyte/macrophages. Int J Mol Med 34(1):283–290

    CAS  PubMed  Google Scholar 

  135. Xiao M, Men LN, Xu MG et al (2014) Berberine protects endothelial progenitor cell from damage of TNF-α via the PI3K/AKT/eNOS signaling pathway. Eur J Pharmacol 743:11–16

    Article  CAS  PubMed  Google Scholar 

  136. Wu YH, Chuang SY, Hong WC et al (2012) Berberine reduces leukocyte adhesion to LPS-stimulated endothelial cells and VCAM-1 expression both in vivo and in vitro. Int J Immunopathol Pharmacol 25:741–750

    CAS  PubMed  Google Scholar 

  137. Kulkarni SK, Dhir A (2010) Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders. Phytother Res 24(3):317–324

    Article  CAS  PubMed  Google Scholar 

  138. Kulkarni SK, Dhir A (2008) On the mechanism of antidepressant-like action of berberine chloride. Eur J Pharmacol 589:163–172

    Article  CAS  PubMed  Google Scholar 

  139. Peng WH, Lo KL, Lee YH, Hung TH, Lin YC (2007) Berberine produces antidepressant-like effects in the forced swim test and in the tail suspension test in mice. Life Sci 81:933–938

    Article  CAS  PubMed  Google Scholar 

  140. Kong LD, Cheng CH, Tan RX (2001) Monoamine oxidase inhibitors from rhizoma of Coptis chinensis. Planta Med 67:74–76

    Article  CAS  PubMed  Google Scholar 

  141. Kumar A, Ekavali Chopra K et al (2015) Current knowledge and pharmacological profile of berberine: an update. Eur J Pharmacol 761:288–297

    Article  CAS  PubMed  Google Scholar 

  142. Kupeli E, Kosar M, Yesilada E, Hüsnü K, Başer C (2002) A comparative study on the anti-inflammatory, antinociceptive and antipyretic effects of isoquinoline alkaloids from the roots of Turkish berberis species. Life Sci 72:645–657

    Article  CAS  PubMed  Google Scholar 

  143. Chen C, Yu Z, Li Y, Fichna J, Storr M (2014) Effects of berberine in the gastrointestinal tract—a review of actions and therapeutic implications. Am J Chin Med 42(5):1053–1070

    Article  CAS  PubMed  Google Scholar 

  144. Chan E (1993) Displacement of bilirubin from albumin by berberine. Biol Neonat 63:201–208

    Article  CAS  Google Scholar 

  145. Tan YZ, Wu AC, Tan BY et al (2002) Study on the interactions of berberine displace other drug from their plasma proteins binding sites. Chin Pharmacol Bull 18:576–578

    CAS  Google Scholar 

  146. Xin HW, Wu XC, Li Q et al (2006) The effects of berberine on the pharmacokinetics of cyclosporine A in healthy volunteers. Methods Find Exp Clin Pharmacol 28:25–29

    Article  CAS  PubMed  Google Scholar 

  147. Wu X, Lu Q, Xin H, Zhong M (2005) Effects of berberine on the blood concentration of cyclosporine A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol 61:567–572

    Article  CAS  PubMed  Google Scholar 

  148. Cicero AF, Tartagni E, Ertek S (2014) Safety and tolerability of injectable lipid-lowering drugs: a review of available clinical data. Expert Opin Drug Saf 13(8):1023–1030

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Cardiovascular Disease Prevention Research Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Via Albertoni 15, 40138, Bologna, Italy

    Arrigo F. G. Cicero & Alessandra Baggioni

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  1. Arrigo F. G. Cicero
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  2. Alessandra Baggioni
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Correspondence to Arrigo F. G. Cicero .

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  1. Banaras Hindu University , Varanasi, Uttar Pradesh, India

    Subash Chandra Gupta

  2. MD Anderson Cancer Center, University of Texas, Houston, Texas, USA

    Sahdeo Prasad

  3. Anti-Inflammation Research Institute, San Diego, California, USA

    Bharat B. Aggarwal

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Cicero, A.F.G., Baggioni, A. (2016). Berberine and Its Role in Chronic Disease. In: Gupta, S., Prasad, S., Aggarwal, B. (eds) Anti-inflammatory Nutraceuticals and Chronic Diseases. Advances in Experimental Medicine and Biology, vol 928. Springer, Cham. https://doi.org/10.1007/978-3-319-41334-1_2

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