A review of the effects of Berberis vulgaris and its major component, berberine, in metabolic syndrome

Authors

1 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran

3 Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Metabolic syndrome (MetS), characterized by a cluster of metabolic abnormalities including hypertension, obesity, type 2 diabetes mellitus (T2DM) and dyslipidemia, is a well-known cardiovascular risk factor (CVRF). Cardiovascular disease (CVD) represents a massive healthcare burden worldwide. In recent years, with regard to the adverse effects of synthetic drugs, increasing attention has been paid by researchers to herbal medicines for a variety of disorders such as CVD. A large body of literature supports different pharmacological actions of Berberis vulgaris (B. vulgaris) and its active component, berberine (BBR), such as antidiabetic, antiobesity, hypotensive and hypolipidemic properties that could be interesting in the management of MetS associated with high CVD risk. Numerous preclinical in vitro and in vivo studies support all these effects. In this review, we evaluated the most related original articles to discover the role of B. vulgaris on various constituents of MetS and CVRF comprising dyslipidemia, obesity, high blood pressure and high blood glucose.
This review suggests a potential role of B. vulgaris and BBR in the managing of MetS; nevertheless more investigations, especially reliable clinical trials, need to be accomplished to evaluate their effectiveness.

Keywords

References

1. Reaven GM. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-1607.
2. DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991; 14: 173-194.
3. Lemieux I, Pascot A, Couillard C, Lamarche Bt, Tchernof A, Alméras N, et al. Hypertriglyceridemic waist: a marker of the atherogenic metabolic triad (hyperinsulinemia; hyperapolipoprotein B; small, dense LDL) in men. Circulation 2000; 102: 179-84.
4.  Kaplan NM. The deadly quartet. Upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med 1989; 149: 1514-1520.
5. Grundy SM, Hansen B, Smith SC, Cleeman JI, Kahn RA, American Heart Association, National Heart, Lung, and Blood Institute, American Diabetes Association. Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. Arterioscler Thromb Vasc Biol 2004; 109: 551-56.
6. Alberti KGM, Zimmet P, Shaw J, Group IETFC. The metabolic syndrome—a new worldwide definition. The Lancet 2005; 366: 1059-1062.
7. Grundy S, Cleeman J, Daniels S, Donato K, Eckel R, Franklin B, et al. American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112: 2735-2752.
8. Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640-45.
9. Mamikutty N, Thent ZC, Sapri SR, Sahruddin NN, Mohd Yusof MR, Haji Suhaimi F. The establishment of metabolic syndrome model by induction of fructose drinking water in male wistar rats. Biomed Res Int 2014; 2014: 263897.
10. O'Flaherty M, Buchan I, Capewell S. Contributions of treatment and lifestyle to declining CVD mortality: why have CVD mortality rates declined so much since the 1960s? Heart 2013; 99: 159-162.
11. Gurib-Fakim A. Medicinal plants: Traditions of yesterday and drugs of tomorrow. Mol Aspects Med 2006; 27: 1-93.
12. Shrivastava R, Agrawal R, Parveen Z. A review on therapeutic applications of Nigella sativa. J Chem Chem Sci 2011; 1: 241-248.
13. Akaberi M, Hosseinzadeh H. Grapes (Vitis vinifera) as a potential candidate for the therapy of the metabolic syndrome. Phytother Res 2016: 30: 540–556.
14. Razavi BM, Hosseinzadeh H. A review of the effects of Nigella sativa L. and its constituent, thymoquinone, in metabolic syndrome. J Endocrinol Invest 2014; 37: 1031-1040.
15. Hosseinzadeh H, Nassiri-Asl M. Review of the protective effects of rutin on the metabolic function as an important dietary flavonoid. J Endocrinol Invest 2014; 37: 783-788.
16. Hosseini A, Hosseinzadeh H. A review on the effects of Allium sativum (Garlic) in metabolic syndrome. J Endocrinol Invest 2015; 38: 1147-1157.
17. Rounsaville TJ, Ranney TG. Ploidy levels and genome sizes of Berberis L. and Mahonia nutt. species, hybrids, and cultivars. HortScience 2010; 45: 1029-1033.
18. Kafi M, Balendari A. Berberis Production and Processing. Ferdowsi University Press, Mashhad, Iran (2004) p. 210.
19. Mokhber-Dezfuli N, Saeidnia S, Gohari AR, Kurepaz-Mahmoodabadi M. Phytochemistry and pharmacology of Berberis species. Pharmacogn Rev 2014; 8: 8-15.
20. Drofler H, Roselt G. The dictionary of healing plants. New  York: Blandford Press; 1989.
21. Arayne MS, Sultana N, Bahadur SS. The berberis story: Berberis vulgaris in therapeutics. Pak J Pharm Sci 2007; 20: 83-92.
22. Tomosaka H, Chin Y-W, Salim AA, Keller WJ, Chai H, Kinghorn AD. Antioxidant and cytoprotective compounds from Berberis vulgaris (barberry). Phytother Res 2008; 22: 979-981.
23. Imanshahidi M, Hosseinzadeh H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother Res 2008; 22: 999-1012.
24. Hajzadeh M, Rajaei Z, Shafiee S, Alavinejhad A, Samarghandian S, Ahmadi M. Effect of barberry fruit (Berberis vulgaris) on serum glucose and lipids in streptozotocin-diabetic rats. Pharmacologyonline 2011; 1: 809-817.
25. Potdar D, Hirwani RR, Dhulap S. Phyto-chemical and pharmacological applications of Berberis aristata. Fitoterapia 2012; 83: 817-830.
26. Nassiri-Asl M, Hosseinzadeh H, Mortazavi SR. Effects of Berberis vulgaris fruit extracts and its active component, berberine, on morphine dependence, hypnosis and locomotor activity in mice. Pharmacologyonline 2007; 1: 190-202.
27. Imenshahidi M, Qaredashi R, Hashemzaei M, Hosseinzadeh H. Inhibitory effect of Berberis vulgaris aqueous extract on acquisition and reinstatement effects of morphine in conditioned place preferences (CPP) in mice. Jundishapur J Nat Pharm Prod 2014; 9: 1-6.e16145.
28. Mohammadi A, Sahebkar A, Kermani T, Zhilaee M, Tavallaie S, Ghayour Mobarhan M. Barberry administration and pro-oxidant–antioxidant balance in patients with metabolic syndrome. Iran Red Crescent Med J 2014; 16: e16786.
29. Gorval LM, Grishkovets VI. Alkaloids of some species of the genus Berberis introduced into the Crimea. Chem Nat Compd 1999; 35: 223-4.
30. Amin AH, Subbaiah TV, Abbasi KM. Berberine sulfate: antimicrobial activity, bioassay, and mode of action. Can J Microbiol 1969; 15: 1067-76.
31. Ni W-J, Ding H-H, Tang L-Q. Berberine as a promising anti-diabetic nephropathy drug: An analysis of its effects and mechanisms. Eur J Pharmacol 2015; 760: 103-12.
32. Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metab Clin Exp 2008; 57: 712-7.
33. Cui G, Qin X, Zhang Y, Gong Z, Ge B, Zang YQ. Berberine differentially modulates the activities of ERK, p38 MAPK, and JNK to suppress Th17 and Th1 T cell differentiation in type 1 diabetic mice. J Biol Chem 2009; 284: 28420-9.
34. Freile ML, Giannini F, Pucci G, Sturniolo A, Rodero L, Pucci O, et al. Antimicrobial activity of aqueous extracts and of berberine isolated from Berberis heterophylla. Fitoterapia 2003; 74: 702-5.
35. Wang N, Feng Y, Zhu M, Tsang C-M, Man K, Tong Y, et al. Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: The cellular mechanism. J Cell Biochem 2010; 111: 1426-36.
36. Goff DC, Jr., Bertoni AG, Kramer H, Bonds D, Blumenthal RS, Tsai MY, et al. Dyslipidemia prevalence, treatment, and control in the Multi-Ethnic Study of Atherosclerosis (MESA): gender, ethnicity, and coronary artery calcium. Circulation 2006; 113: 647-56.
37. Gulati OP. Pycnogenol® in metabolic syndrome and related disorders. Phytother Res 2015; 29: 949-68.
38. Dong S-F, Hong Y, Liu M, Hao Y-Z, Yu H-S, Liu Y, et al. Berberine attenuates cardiac dysfunction in hyperglycemic and hypercholesterolemic rats. Eur J Pharmacol 2011; 660: 368-74.
39. Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med 2004; 10: 1344-51.
40. Kong W-J, Wei J, Zuo Z-Y, Wang Y-M, Song D-Q, You X-F, et al. Combination of simvastatin with berberine improves the lipid-lowering efficacy. Metabolism 2008; 57: 1029-37.
41. Taheri S, Zarei A, Changizi Ashtiyani S, Rezaei A, Zaheiri S. Evaluation of the effects of hydroalcoholic extract of Berberis vulgaris root on the activity of liver enzymes in male hypercholesterolemic rats. Avicenna J Phytomed 2012; 2: 153-61.
42. Wang Y, Yi X, Ghanam K, Zhang S, Zhao T, Zhu X. Berberine decreases cholesterol levels in rats through multiple mechanisms, including inhibition of cholesterol absorption. Metabolism 2014; 63: 1167-77.
43. Chang X, Yan H, Fei J, Jiang M, Zhu H, Lu D, et al. Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats. J Lipid Res 2010; 51: 2504-15.
44. Zhou Y, Cao S, Wang Y, Xu P, Yan J, Bin W, et al. Berberine metabolites could induce low density lipoprotein receptor up-regulation to exert lipid-lowering effects in human hepatoma cells. Fitoterapia 2014; 92: 230-7.
45. Zhao W, Xue R, Zhou Z-X, Kong W-J, Jiang J-D. Reduction of blood lipid by berberine in hyperlipidemic patients with chronic hepatitis or liver cirrhosis. Biomed Pharmacother 2008; 62: 730-1.
46. Mazza A, Lenti S, Schiavon L, Zuin M, D’Avino M, Ramazzina E, et al. Nutraceuticals for serum lipid and blood pressure control in hypertensive and hypercholesterolemic subjects at low cardiovascular risk. Adv Ther 2015; 32: 680-90.
47. Zhu L, Li H. Therapeutic efficacy of combined Berberine and Glipizide on type 2 diabete. J Clin Res 2007; 1: 20.
48. Shanobin J, Lirong T, Yi S. Interventioal effect of berberine liposome on impaired glucose tolerance accompanied with hyperlipemia. J Pract Tradit Chin Med 2007; 8: 008.
49. Brusq J-M, Ancellin N, Grondin P, Guillard R, Martin S, Saintillan Y, et al. Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine. J Lipid Res 2006; 47: 1281-8.
50. Grover SA, Kaouache M, Rempel P, Joseph L, Dawes M, Lau DCW, et al. Years of life lost and healthy life-years lost from diabetes and cardiovascular disease in overweight and obese people: a modelling study. Lancet Diabetes Endocrinol 2015; 3: 114-22.
51. El-Sayed MM, Ghareeb DA, Talat HA, Sarhan EM. High fat diet induced insulin resistance and elevated retinol binding protein 4 in female rats; treatment and protection with Berberis vulgaris extract and vitamin A. Pak J Pharm Sci 2013; 26: 1189-95.
52. Hu Y, Davies GE. Berberine inhibits adipogenesis in high-fat diet-induced obesity mice. Fitoterapia 2010; 81: 358-66.
53. Iloon Kashkooli R, Najafi SS, Sharif F, Hamedi A, Hoseini Asl MK, Najafi Kalyani M, et al. The effect of Berberis vulgaris extract on transaminase activities in non-alcoholic fatty liver disease. Hepat Mon 2015; 15: e25067.
54. World Health Organization. Prevention of cardiovascular disease: guideline for assessment and management of cardiovascular risk. 2007.
55. Psaty BM, Smith NL, Siscovick DS, et al. Health outcomes associated with antihypertensive therapies used as first-line agents: A systematic review and meta-analysis. JAMA 1997; 277: 739-45.
56. Guo Z, Sun H, Zhang H, Zhang Y. Anti-hypertensive and renoprotective effects of berberine in spontaneously hypertensive rats. Clin Exp Hypertens 2015; 37: 332-9.
57. 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 2005; 19: 222-5.
58. Chun YT, Yip TT, Lau KL, Kong YC, Sankawa U. A biochemical study on the hypotensive effect of berberine in rats. General Pharmacology: The Vascular System 1979; 10: 177-82.
59. Kang DG, Sohn EJ, Kwon EK, Han JH, Oh H, Lee HS. Effects of berberine on angiotensin-converting enzyme and NO/cGMP system in vessels. Vascul Pharmacol 2002; 39: 281-6.
60. 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 1992; 105: 1014-9.
61. Marin-Neto JA, Maciel BC, Secches AL, Gallo Junior L. Cardiovascular effects of berberine in patients with severe congestive heart failure. Clin Cardiol 1988; 11: 253-60.
62. Trimarco V, Cimmino C, Santoro M, Pagnano G, Manzi M, Piglia A, et al. Nutraceuticals for blood pressure control in patients with high-normal or grade 1 hypertension. High Blood Press Cardiovasc Prev 2012; 19: 117-22.
63. Pang B, Zhao L-H, Zhou Q, Zhao T-Y, Wang H, Gu C-J, et al. Application of berberine on treating type 2 diabetes mellitus. Int J Endocrinol 2015; 2015: 12.
64. Gu Y, Zhang Y, Shi X, Li X, Hong J, Chen J, et al. Effect of traditional Chinese medicine berberine on type 2 diabetes based on comprehensive metabonomics. Talanta 2010; 81: 766-72.
65. García-Fontana B, Morales-Santana S, Díaz Navarro C, Rozas-Moreno P, Genilloud O, Vicente Pérez F, et al. Metabolomic profile related to cardiovascular disease in patients with type 2 diabetes mellitus: A pilot study. Talanta 2016; 148: 135-43.
66. Abd El-Wahab A, Ghareeb D, Sarhan E, Abu-Serie M, El Demellawy M. In vitro biological assessment of Berberis vulgaris and its active constituent, berberine: antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effects. BMC Complement Altern Med 2013; 13: 218.
67. Shidfar F, Ebrahimi SS, Hosseini S, Heydari I, Shidfar S, Hajhassani G. The Effects of Berberis vulgaris fruit extract on serum lipoproteins, apoB, apoA-I, homocysteine, glycemic control and total antioxidant capacity in type 2 diabetic patients. Iran J Pharm Res 2012; 11: 643-52.
68. Zhang H, Wei J, Xue R, Wu J-D, Zhao W, Wang Z-Z, et al. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism 2010; 59: 285-92.
69. Zhang Y, Li X, Zou D, Liu W, Yang J, Zhu N, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab 2008; 93: 2559-65.
70. Lan J, Zhao Y, Dong F, Yan Z, Zheng W, Fan J, et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol 2015; 161: 69-81.
71. Zhang M, Lv X, Li J, Meng Z, Wang Q, Chang W, et al. Sodium caprate augments the hypoglycemic effect of berberine via AMPK in inhibiting hepatic gluconeogenesis. Mol Cell Endocrinol 2012; 363: 122-30.
72. Zhou J, Zhou S, Tang J, Zhang K, Guang L, Huang Y, et al. Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. Eur J Pharmacol 2009; 606: 262-8.
73. Chatuphonprasert W, Lao-ong T, Jarukamjorn K. Improvement of superoxide dismutase and catalase in streptozotocin–nicotinamide-induced type 2-diabetes in mice by berberine and glibenclamide. Pharm Biol 2014; 52: 419-27.
74. Zhang Q, Xiao X, Feng K, Wang T, Li W, Yuan T, et al. Berberine moderates glucose and lipid metabolism through multipathway mechanism. Evid Based Complement Alternat Med 2011; 2011: 10.
75. Lu S-S, Yu Y-L, Zhu H-J, Liu X-D, Liu L, Liu Y-W, et al. Berberine promotes glucagon-like peptide-1 (7–36) amide secretion in streptozotocin-induced diabetic rats. J Endocrinol 2009; 200: 159-65.
76. Cicero AF, Tartagni E. Antidiabetic properties of berberine: from cellular pharmacology to clinical effects. Hosp Pract 2012; 40: 56-63.
77. Chang W, Zhang M, Li J, Meng Z, Wei S, Du H, et al. Berberine improves insulin resistance in cardiomyocytes via activation of 5′-adenosine monophosphate-activated protein kinase. Metabolism 2013; 62: 1159-67.
78. Ko B-S, Choi SB, Park SK, Jang JS, Kim YE, Park S. Insulin sensitizing and insulinotropic action of berberine from Cortidis rhizoma. Biol Pharm Bull 2005; 28: 1431-7.
79. Pan G-Y, Huang Z-J, Wang G-J, Fawcett JP, Liu X-D, Zhao X-C, et al. The antihyperglycaemic activity of berberine arises from a decrease of glucose absorption. Planta Med 2003; 69: 632-6.
80. Lou T, Zhang Z, Xi Z, Liu K, Li L, Liu B, et al. Berberine inhibits inflammatory response and ameliorates insulin resistance in hepatocytes. Inflammation 2011; 34: 659-67.
81. Yin J, Gao Z, Liu D, Liu Z, Ye J. Berberine improves glucose metabolism through induction of glycolysis. Am J Physiol Endocrinol Metab 2008; 294: E148-E56.
82. Jeong HW, Hsu KC, Lee J-W, Ham M, Huh JY, Shin HJ, et al. Berberine suppresses proinflammatory responses through AMPK activation in macrophages. Am J Physiol Endocrinol Metab 2009; 296: E955-E64.
83. Han J, Lin H, Huang W. Modulating gut microbiota as an anti-diabetic mechanism of berberine. Med Sci Monit Basic Res 2011; 17: RA164-RA7.
84. Changizi Ashtiyani S, Zarei A, Taheri S, Rezaei A, Golshan M, Ghafarzadegan R. A comparative study of hypolipidemic activities of the extracts of Melissa officinalis and Berberis vulgaris in rats. J Med Plant 2013; 12: 38-47.
85. Zheng B, Wei J, Jiang J, GONG H-h, ZHANG R-s. The therapeutic effects of combination of simvastatin with berberine on the patients with hyperlipemia. Acta Univ Med Nanjing (Nat Sci) 2009; 29: 1493-7.
86. Ye W. Clinical efficacy of berberine treatment of diabetes. Mod Hosp 2010; 10: 9-10.
87. JANG C-S. The action of berberine on mammalian hearts. J Pharmacol Exp Ther 1941; 71: 178-86.
88. Kong W-J, Zhang H, Song D-Q, Xue R, Zhao W, Wei J, et al. Berberine reduces insulin resistance through protein kinase C–dependent up-regulation of insulin receptor expression. Metabolism 2009; 58: 109-19.
89. Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, et al. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes 2006; 55: 2256-64.
90. Liu C, Wang Z, Song Y, Wu D, Zheng X, Li P, et al. Effects of berberine on amelioration of hyperglycemia and oxidative stress in high glucose and high fat diet-induced diabetic hamsters in vivo. Biomed Res Int 2015; 2015: 9.
91. Di Pierro F, Bellone I, Rapacioli G, Putignano P. Clinical role of a fixed combination of standardized Berberis aristata and Silybum marianum extracts in diabetic and hypercholesterolemic patients intolerant to statins. Diabetes Metab Syndr Obes 2015; 8: 89-96.
92. Chen G, Lu F, Xu L, Dong H, Yi P, Wang F, et al. The anti-diabetic effects and pharmacokinetic profiles of berberine in mice treated with Jiao-Tai-Wan and its compatibility. Phytomedicine 2013; 20: 780-6.
93. Dai P, Wang J, Lin L, Zhang Y, Wang Z. Renoprotective effects of berberine as adjuvant therapy for hypertensive patients with type 2 diabetes mellitus: Evaluation via biochemical markers and color Doppler ultrasonography. Exp Ther Med 2015; 10: 869-76.
94. Wang Y, Huang Y, Lam KSL, Li Y, Wong WT, Ye H, et al. Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase. Cardiovasc Res 2009; 82: 484-92.
Iranian Journal of Basic Medical Sciences
Volume 20, Issue 5
May 2017
Pages 557-568

Files

Share

How to cite

Statistics