A new TCM formula FTZ lowers serum cholesterol by regulating HMG-CoA reductase and CYP7A1 in hyperlipidemic rats

Ethnopharmacological relevance: Based on a theory of Chinese Medicine, Regulating Gan (liver) to lower lipids that is in brief to regulate the lipid metabolic related factors in the liver will improve serum lipid profile, we have developed Fufang Zhenzhu Tiao Zhi (FTZ) which includes eight herbs that are quality assured. FTZ has been developed with the potential to correct abnormal lipid metabolism. This Chinese herbal medicine has been prescribed for 20 years, which has been issued patent and clinically proven for use in the treatment of dyslipidemia. Aim of the study: To investigate the cholesterol-lowering effect and the mode of action of FTZ extract on high lipid diet induced hyperlipidemic rats. Materials and methods: The FTZ was prepared by alcohol and water extraction of eight herbs that have been quality-controlled according to the protocol. The cholesterol-lowering effect of FTZ was evaluated on SD rats fed with high-lipid diet. RT-PCR and western blot were used to analyze the gene expression of cholesterol metabolism-related enzymes including HMG-CoA reductase and cholesterol 7 alpha-hydroxylase (CYP7A1) in the livers of the rats. The activity of HMG-CoA reductase and CYP7A1 were assessed by colorimetrical method and by quantification of the cholesterol metabolite of CYP7A1 using HPLC analysis respectively. Results and conclusions: FTZ significantly decreased the levels of serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), whilst elevated the serum high-density lipoprotein cholesterol (HDL-C) and decreased serum atherogenic index (A.I.) values in high lipid diet induced hyperlipidemic rats. Furthermore, FTZ showed significant antihyperlipidemic effect by at least three pathways in the high lipid diet induced hyperlipidemic rats: (1) upregulating the gene expression and activity of CYP7A1 which promotes the conversion of cholesterol into bile acid; (2) downregulating the gene expression and activity of HMG-CoA reductase to reduce de novo synthesis of cholesterol; (3) increasing the cholesterol excretion from feces. In these three pathways, HMG-CoA reductase and CYP7A1 are two pivotal enzymes in lipid cholesterol metabolism and are expressed mainly in hepatic cells, which support our new TCM treatment strategy: Modulating Liver to Treat Hyperlipemia. (C) 2011 Elsevier Ireland Ltd. All rights reserved.