期刊论文详细信息
Lipids in Health and Disease
The effects of berberine on hyperhomocysteinemia and hyperlipidemia in rats fed with a long-term high-fat diet
Xin Gao1  Teng-fang Zhu2  Hua Bian1  Ming-feng Xia1  Qiong Xu1  Hong-mei Yan1  Xin-xia Chang1 
[1]Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China
[2]Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China
关键词: Hyperlipidemia;    Hyperhomocysteinemia;    Berberine;   
Others  :  1160258
DOI  :  10.1186/1476-511X-11-86
 received in 2012-02-12, accepted in 2012-06-25,  发布年份 2012
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【 摘 要 】

Background

The study was undertaken to examine the effects of berberine (BBR) on serum homocysteine, lipids and the aortic lesion in Sprague–Dawley (SD) rats fed with a long-term high-fat diet (HFD).

Methods

Healthy male SD rats weighing 190-210 g received randomly standard diet or a high-fat diet for 24 weeks. After 8 weeks of feeding, rats fed with HFD were randomized to receive berberine (200 mg · kg-1· day-1) or vehicle by gavage for 16 weeks. After overnight fasting, all rats were sacrificed and total blood samples were also collected for determinant of fasting serum homocysteine (Hcy), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-c) levels. The aorta was stained with hematoxylin and eosin (HE) and Sudan Ш to evaluate aortic lesion. The livers were dissected out and snap-frozen in liquid nitrogen for hepatic TC content and molecular analysis. 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), Lipoprotein receptors and apolipoproteins gene expression in the liver were determined by real-time PCR.

Results

Intragastrical administration with berberine for 16 weeks lowered serum Hcy in rats fed with a high-fat diet. In parallel, it also decreased body weight and improved serum TC and LDL-c. Berberine also tended to decrease hepatic cholesterol. Consistently, berberine also upregulated LDL receptor (LDLR) mRNA level and suppressed HMGR gene expression. Meanwhile, upon berberine-treated rats, there was a significant increase in apolipoprotein E (apoE) mRNA, but no change in apoAI and scavenger receptor (SR) mRNA in the liver. Further, no atherosclerotic lesions were developed in berberine-treated rats for 16 weeks.

Conclusion

Berberine can counteract HFD-elicited hyperhomocysteinemia and hyperlipidemia partially via upregulating LDLR and apoE mRNA levels and suppressing HMGR gene expression.

【 授权许可】

   
2012 Chang et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]McCully KS: Hyperhomocysteinemia and arteriosclerosis: historical perspectives. Clin Chem Lab Med 2005, 43:980-986.
  • [2]Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, et al.: Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA 1997, 277:1775-1781.
  • [3]McCully KS: Homocysteine and vascular disease. Nat Med 1996, 2:386-389.
  • [4]Guthikonda S, Haynes WG: Homocysteine as a novel risk factor for atherosclerosis. Curr Opin Cardiol 1999, 14:283-291.
  • [5]Chen QM, Xie MZ: Studies on the hypoglycemic effect of Coptis chinensis and berberine. Yao Xue Xue Bao 1986, 21:401-406.
  • [6]Kim WS, Lee YS, Cha SH, Jeong HW, Choe SS, Lee MR, et al.: Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity. Am J Physiol 2009, 296:E812-E819.
  • [7]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. Nature medicine 2004, 10:1344-1351.
  • [8]Yin J, Gao ZG, Liu D, Liu ZJ, Ye JP: Berberine improves glucose metabolism through induction of glycolysis. Am J Physiol Endocrinol Metab 2008, 294:E148-E156.
  • [9]Kong WJ, Zhang H, Song DQ, Xue R, Zhao W, Wei J, et al.: Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. Metab Clin Exp 2009, 58:109-119.
  • [10]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, 55:2256-2264.
  • [11]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. Jounal of Lipid Research 2010, 51:2504-2515.
  • [12]Li K, Yao WQ, Zheng XD, Liao K: Berberine promotes the development of atherosclerosis and foam cell formation by inducing scavenger receptor A expression in macrophage. Cell Research 2009, 19:1006-1017.
  • [13]Zhang SH, Reddick RL, Piedrahita JA, Maeda N: Spontaneous Hypercholesterolemia and Arterial Lesions in Mice Lacking Apolipoprotein-E. Science 1992, 258:468-471.
  • [14]Plump AS, Smith JD, Hayek T, Aaltosetala K, Walsh A, Verstuyft JG, et al.: Severe Hypercholesterolemia and Atherosclerosis in Apolipoprotein-E-Deficient Mice Created by Homologous Recombination in Es Cells. Cell 1992, 71:343-353.
  • [15]Reddick RL, Zhang SH, Maeda N: Atherosclerosis in Mice Lacking Apo-E - Evaluation of Lesional Development and Progression. Arterioscler Thromb 1994, 14:141-147.
  • [16]Boushey CJ, Beresford SA, Omenn GS, Motulsky AG: A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995, 274:1049-1057.
  • [17]Brown MS, Goldstein JL: A receptor-mediated pathway for cholesterol homeostasis. Science 1986, 232:34-47.
  • [18]Russell DW: Cholesterol biosynthesis and metabolism. Cardiovasc Drugs Ther 1992, 6:103-110.
  • [19]Getz GS, Reardon CA: Apoprotein E as a lipid transport and signaling protein in the blood, liver, and artery wall. Journal of Lipid Research 2009, 50:S156-S161.
  • [20]Linton M, Atkinson J, Fazio S: Prevention of Atherosclerosis in Apolipoprotein E-Deficient Mice by Bone Marrow Transplantation Science.. 1995, 267:1034-1037.
  • [21]Adams LA, Angulo P, Lindor KD: Nonalcoholic fatty liver disease. CMAJ 2005, 172(7):899-905.
  • [22]Visser ME, Akdim F, Tribble DL, Nederveen AJ, Kwoh TJ, Kastelein JJP, et al.: Effect of Apolipoprotein-B Synthesis Inhibition on Liver Triglyceride Content in Patients with Familial Hypercholesterolemia. Journal of lipid research 2010, 51(5):1057-1062.
  • [23]Letteron P, Sutton A, Abdellah M, Fromenty B, Pessayre D: Inhibition of microsomal triglyceride transfer protein: another mechanism of drug-induced steatosis in mice. Hepatology 2003, 38:133-140.
  • [24]Hartmann G: Stahelin HB [Hyperlipidemia and atherosclerosis in Switzerland. Results from the "Basler studie" (author's transl)]. Ther Umsch 1980, 37:980-984.
  • [25]Nakayama S, Sakashita M, Tonooka M, Gotoh H, Yasuhara H, Sakamoto K: Experimental hyperlipidemia and atherosclerosis induced by cholesterol diet in SPF Japanese white rabbits. Jpn J Pharmacol 1983, 33:279-289.
  • [26]Rogers WR, Carey KD, McMahan CA, Montiel MM, Mott GE, Wigodsky HS, et al.: Cigarette smoking, dietary hyperlipidemia, and experimental atherosclerosis in the baboon. Exp Mol Pathol 1988, 48:135-151.
  • [27]Kuo PT: Hyperlipidemia in atherosclerosis. Dietary and drug treatment. Med Clin North Am 1970, 54:657-669.
  • [28]Chang PY, Lu SC, Lee CM, Chen YJ, Dugan TA, Huang WH, et al.: Homocysteine inhibits arterial endothelial cell growth through transcriptional downregulation of fibroblast growth factor-2 involving G protein and DNA methylation. Circ Res 2008, 102:933-941.
  • [29]Wang GP, Woo CWH, Sung FL, Siow YL OK: Increased monocyte adhesion to aortic endothelium in rats with hyperhomocysteinemia - Role of chemokine and adhesion molecules. Arterioscler Thromb Vasc Biol 2002, 22:1777-1783.
  • [30]Scalia R, Gooszen ME, Jones SP, Hoffmeyer M, Rimmer DM, Trocha SD, et al.: Simvastatin exerts both anti-inflammatory and cardioprotective effects in apolipoprotein E-deficient mice. Circulation 2001, 103:2598-2603.
  • [31]Folch J, Lees M, Sloane Stanley GH: A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957, 226:497-509.
  • [32]Jiang MH, Fei J, Lan MS, Lu ZP, Liu M, Fan WW, et al.: Hypermethylation of hepatic Gck promoter in ageing rats contributes to diabetogenic potential. Diabetologia 2008, 51:1525-1533.
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