title: Hypocholesterolemia of Rhizoma Coptidis alkaloids is related to the bile acid by up-regulated CYP7A1 in hyperlipidemic rats.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: Weijian
authors.initials: W
authors.lastname: Bei
authors.forename: Yinming
authors.initials: Y
authors.lastname: Hu
authors.forename: Le
authors.initials: L
authors.lastname: Cao
authors.forename: Lihua
authors.initials: L
authors.lastname: Huang
authors.forename: Laiyou
authors.initials: L
authors.lastname: Wang
authors.forename: Duosheng
authors.initials: D
authors.lastname: Luo
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Xi
authors.initials: X
authors.lastname: Yao
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Liu
authors.forename: Jiao
authors.initials: J
authors.lastname: Guo
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D039323:Coptis / Q000737:chemistry; D004032:Diet / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005243:Feces; D005786:Gene Expression Regulation / Q000187:drug effects; D006949:Hyperlipidemias / Q000188:drug therapy / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000470:Alkaloids; D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; D008078:Cholesterol, LDL; D047493:PPAR alpha; D010936:Plant Extracts; D018160:Receptors, Cytoplasmic and Nuclear; D014280:Triglycerides; D000099150:Receptor, Farnesoid X-Activated; C532838:CYP7A1 protein, rat