Hypolipidemic effect of SIPI-7623,a derivative of an extract from oriental wormwood,through farnesoid X receptor antagonism

作     者：DENG Yi-Fang HUANG Xiao-Ling SU Mei YU Peng-Xia ZHANG Zhen LIU Quan-Hai WANG Guo-Ping LIU Min-Yu 

作者机构：Department of PharmacologyShanghai Institute of Pharmaceutical Industry Jiangsu Carephar Pharmaceutical Co.Ltd. 

出 版 物：《Chinese Journal of Natural Medicines》 (中国天然药物（英文版）)

年 卷 期：2018年第16卷第8期

页      面：572-579页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1005[医学-中医学] 100706[医学-药理学] 1002[医学-临床医学] 0703[理学-化学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by Shanghai Committee of Science and Technology(No.16431903500) 

主　　题：Farnesoid X receptor antagonist Hypolipidemic Bile acid enterohepatic circulation Cholesterol-7-alpha-hydroxylase Sterol-regulatory element-binding protein 1c 

摘      要：Farnesoid X receptor(FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription *** a metabolic regulator,FXR plays key roles in bile acid and cholesterol metabolism and lipid and glucose ***,FXR is a potential drug target for several metabolic syndromes,especially those related to lipidemia *** the present study,we identified small molecule SIPI-7623,a derivative of an extract from Oriental wormwood(Artemisia capillaris),and found that it specifically upregulated the expression of cholesterol-7-alpha-hydroxylase(CYP7 A1),downregulated the expression of sterol-regulatory element-binding protein 1 c(SREBP-1 c) in the liver,and inhibited the expression of ileal bile acid binding-protein(IBABP) in the ileum of *** found that inhibition of FXR by SIPI-7623 decreased the level of cholesterol and ***-7623 reduced the levels of cholesterol and triglyceride in in vitro Hep G2 cell models,ameliorated diet-induced atherosclerosis,and decreased the serum lipid content on rats and rabbits model of atherosclerosis in ***,SIPI-7623 decreased the extent of atherosclerotic *** resutls demonstrated that antagonism of the FXR pathway can be employed as a therapeutic strategy to treat metabolic diseases such as hyperlipidemia and *** conclusion,SIPI-7623 could be a promising lead compound for development of drugs to treat hyperlipidemia and atherosclerosis.