Key Unit of Modulating Liver to Treat Hyperlipemia SATCM, State Administration of Traditional Chinese Medicine, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China.
Phytomedicine. 2012 Jun 15;19(8-9):686-92. doi: 10.1016/j.phymed.2012.03.011. Epub 2012 May 2.
This study is to investigate the cholesterol-lowering effect and the new mode of action of coptis alkaloids on high lipid diet-induced hyperlipidemic rats. Coptis alkaloids extract (CAE) was prepared by alcohol extraction from Rhizoma Coptidis that have been quality-controlled according to the protocol. The cholesterol-lowering effect of CAE was evaluated on SD rats fed with high-lipid diet. Serum level of lipid, Bile acid and cholesterol in the liver and feces of the rats were measured using colorimetric assay kit. RT-PCR and Western blot were used to analyze the mRNA and protein expression of cholesterol metabolism-related genes including cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptor-alpha (PPARα) and farnesoid X receptor (FXR) in the livers of the rats. A HPLC analysis was used to assess the activity of CYP7A1. The results showed that CAE reduced the levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C). CYP7A1 gene expression and its activity was up-regulated dose-dependently accompanying with the increased level of bile acid and the reduced cholesterol level in the livers of the CAE treated hyperlipidemic rats. Meanwhile, the mRNA expression of PPARα was also up-regulated in dose-dependent way accompanying the down-modulation of the FXR mRNA expression in the livers of the CAE treated hyperlipidemic rats. The results indicate that the cholesterol-lowering effect of coptis alkaloid extract is at least partly attributed to its promoting the cholesterol conversion into bile acids by up-regulating the gene expression of CYP7A1 and thus increasing its activity in the liver of the hyperlipidemic rats, which might related to the positive regulation of PPARα and the negative modulation of FXR.
本研究旨在探讨黄连生物碱降低胆固醇的作用及其对高脂饮食诱导的高脂血症大鼠的新作用机制。黄连生物碱提取物（CAE）通过从黄连根茎中用酒精提取制备，该根茎已按照方案进行质量控制。用高脂饮食喂养 SD 大鼠来评估 CAE 的降胆固醇作用。使用比色法试剂盒测定大鼠血清中脂质、胆汁酸和胆固醇水平，以及肝脏和粪便中的胆固醇。采用 RT-PCR 和 Western blot 分析胆固醇代谢相关基因的 mRNA 和蛋白表达，包括胆固醇 7α-羟化酶（CYP7A1）、过氧化物酶体增殖物激活受体-α（PPARα）和法尼醇 X 受体（FXR）。采用 HPLC 分析评估 CYP7A1 的活性。结果表明，CAE 降低了血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）的水平。CYP7A1 基因表达及其活性呈剂量依赖性上调，伴随着胆汁酸水平的增加和 CAE 处理的高脂血症大鼠肝脏中胆固醇水平的降低。同时，CAE 处理的高脂血症大鼠肝脏中 PPARα 的 mRNA 表达也呈剂量依赖性上调，同时 FXR 的 mRNA 表达下调。结果表明，黄连生物碱提取物的降胆固醇作用至少部分归因于其通过上调 CYP7A1 的基因表达促进胆固醇转化为胆汁酸，从而增加其在高脂血症大鼠肝脏中的活性，这可能与 PPARα 的正调节和 FXR 的负调节有关。
