Journal
PHYTOMEDICINE
Volume 19, Issue 8-9, Pages 686-692Publisher
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.phymed.2012.03.011
Keywords
Rhizoma Coptidis alkaloid extract; Hyperlipidemia; Bile acid; Cholesterol 7 alpha-hydroxylase; Peroxisome proliferator-activated; receptor-alpha; Farnesoid X receptor
Categories
Funding
- Natural Sciences Funds, Republic of China [30973913, 2009, 81173626, 2011]
- Guangdong Province - Chinese Education Ministry Industry, Education and Research Cooperation [2009B090300349]
- Guangdong Province Natural Sciences Funds Research Team Project [10351022401000000]
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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 7 alpha-hydroxylase (CYP7A1), peroxisome proliferator-activated receptor-alpha (PPAR alpha) 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 acompanying 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 PPAR alpha was also up-regulated in dose-dependent way acompanying 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 PPAR alpha and the negative modulation of FXR. (C) 2012 Elsevier GmbH. All rights reserved.
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