Effect of Berberine on promoting the excretion of cholesterol in high-fat diet-induced hyperlipidemic hamsters

Journal of Translational Medicine

Research

Shi-Heng Luo¹  Chao Ma¹  Xin Gao²  Yangchao Chen³  Zhen-Xiong Zhao⁴  Jia-Wen Shou⁴  Min Huang⁴  Yan Wang⁴  Chi-Yu He⁴  Jie Fu⁴  Xiao-Yang Li⁴  Ru Feng⁴  Long Ren⁴  Fang Guo⁴  Bao-Ying Wen⁴  Jian-Dong Jiang⁵ 

[1] Beijing Analytical Application Center, Shimadzu (China) Co., Ltd., 100020, Beijing, China;Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, 200032, Shanghai, China;School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China;State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, 100050, Beijing, China;State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, 100050, Beijing, China;Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences/Peking Union Medical College, 100050, Beijing, China;

关键词: Berberine;    Cholesterol;    Hyperlipidemia;    Mechanism;    Excretion;    Bile;   

DOI  :  10.1186/s12967-015-0629-3

 received in 2015-04-18, accepted in 2015-08-04,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundBerberine (BBR), as a new medicine for hyperlipidemia, can reduce the blood lipids in patients. Mechanistic studies have shown that BBR activates the extracellular-signal regulated kinase pathway by stabilizing low-density-lipoprotein receptor mRNA. However, aside from inhibiting the intestinal absorption of cholesterol, the effects of BBR on other metabolic pathways of cholesterol have not been reported. This study aimed to investigate the action of BBR on the excretion of cholesterol in high-fat diet-induced hyperlipidemic hamsters.MethodsGolden hamsters were fed a high-fat diet (HFD) for 6 weeks to induce hyperlipidemia, followed by oral treatment with 50 and 100 mg/kg/day of BBR or 10 and 30 mg/kg/day of lovastatin for 10 days, respectively. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), transaminases, and total bile acid in the serum, liver, bile and feces were measured using an enzyme-linked immunosorbent assay. The cholesterol (as well as coprostanol) levels in the liver, bile and feces were determined by gas chromatography–mass spectrometry.ResultsThe HFD hamsters showed significantly hyperlipidemic characteristics compared with the normal hamsters. Treatment with BBR for 10 days reduced the serum TC, TG and LDL-C levels in HFD hamsters by 44–70, 34–51 and 47–71 %, respectively, and this effect was both dose- and time-dependent. Initially, a large amount of cholesterol accumulated in the hyperlipidemic hamster livers. After BBR treatment, reductions in the liver cholesterol were observed by day 3 and became significant by day 7 at both doses (P < 0.001). Meanwhile, bile cholesterol was elevated by day 3 and significantly increased at day 10 (P < 0.001). BBR promoted cholesterol excretion from the liver into the bile in hyperlipidemic hamsters but not in normal hamsters, and these results provide a link between the cholesterol-lowering effect of BBR with cholesterol excretion into the bile.ConclusionsWe conclude that BBR significantly promoted the excretion of cholesterol from the liver to the bile in hyperlipidemic hamsters, which led to large decreases in the serum TC, TG and LDL-C levels. Additionally, compared with lovastatin, the BBR treatment produced no obvious side effects on the liver function.

【 授权许可】

CC BY   
© Li et al. 2015