Li Xiao-Yang, Zhao Zhen-Xiong, Huang Min, Feng Ru, He Chi-Yu, Ma Chao, Luo Shi-Heng, Fu Jie, Wen Bao-Ying, Ren Long, Shou Jia-Wen, Guo Fang, Chen Yangchao, Gao Xin, Wang Yan, Jiang Jian-Dong
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, 100050, China.
Beijing Analytical Application Center, Shimadzu (China) Co., Ltd., Beijing, 100020, China.
J Transl Med. 2015 Aug 27;13:278. doi: 10.1186/s12967-015-0629-3.
Berberine (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.
Golden 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.
The 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.
We 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.
黄连素（BBR）作为一种治疗高脂血症的新药，可降低患者血脂。机制研究表明，BBR 通过稳定低密度脂蛋白受体 mRNA 激活细胞外信号调节激酶途径。然而，除了抑制肠道对胆固醇的吸收外，BBR 对胆固醇其他代谢途径的影响尚未见报道。本研究旨在探讨 BBR 对高脂饮食诱导的高脂血症仓鼠胆固醇排泄的作用。
将金黄仓鼠喂以高脂饮食（HFD）6 周以诱导高脂血症，随后分别以 50 和 100 mg/kg/天的 BBR 或 10 和 30 mg/kg/天的洛伐他汀口服治疗 10 天。采用酶联免疫吸附测定法测量血清、肝脏、胆汁和粪便中的总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、转氨酶和总胆汁酸水平。通过气相色谱 - 质谱法测定肝脏、胆汁和粪便中的胆固醇（以及粪甾烷醇）水平。
与正常仓鼠相比，HFD 仓鼠表现出明显的高脂血症特征。用 BBR 治疗
