Cycloastragenol improves hepatic steatosis by activating farnesoid X receptor signalling. (July 2017)

• Record Type: Journal Article
• Authors: Gu, Ming; Zhang, Shiying; Zhao, Yuanyuan; Huang, Jinwen; Wang, Yahui; Li, Yin; Fan, Shengjie; Yang, Li; Ji, Guang; Tong, Qingchun; Huang, Cheng
• Is Part Of: Pharmacological research. Volume 121(2017:Jul.)
• Page Start: 22
• Page End: 32
• Publication Date: 2017-07
• Subjects: ALT alanine aminotransferase -- AST aspartate transaminase -- BA bile acid -- DIO diet-induced obesity -- CA cholic acid -- DMSO dimethylsulfoxide -- FXR farnesyl X receptor -- HDL-c high density lipoprotein cholesterol -- HF high-fat -- IPITT intraperitoneal insulin tolerance test -- LDL-c low density lipoprotein cholesterol -- NAFLD non-alcoholic fatty liver disease -- NASH non-alcoholic steatohepatitis -- NF-κB nuclear factor kappa B -- NR nuclear receptor -- MS metabolic disease -- Rosi rosiglitazone -- TBA total bile acid -- TC total cholesterol -- TCA taurocholic acid -- TCDCA tauro-chenodeoxycholic acid -- TG triglyceride -- TUDCA tauro-ursodeoxycholic acid; Cycloastragenol -- Metabolic syndrome -- Non-alcoholic fatty liver disease -- Farnesyl X receptor; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2017.04.021
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: 1. Cycloastragenol stimulated FXR transcription activity. 2. Cycloastragenol lowered blood glucose, serum triglyceride in DIO mice. 3. Cycloastragenol alleviated hepatic steatosis in DIO and MCD mice. Abstract: Non-alcoholic fatty liver disease (NAFLD) has become a global health problem. However, there is no approved therapy for NAFLD. Farnesoid X receptor (FXR) is a potential drug target for treatment of NAFLD. In an attempt to screen FXR agonists, we found that cycloastragenol (CAG), a natural occurring compound in Astragali Radix, stimulated FXR transcription activity. In animal studies, we demonstrated that CAG treatment resulted in obvious reduction of high-fat diet induced lipid accumulation in liver accompanied by lowered blood glucose, serum triglyceride levels and hepatic bile acid pool size. The stimulation of FXR signalling by CAG treatment in DIO mice was confirmed via gene expression and western blot analysis. Molecular docking data further supported the interaction of CAG and FXR. In addition, CAG alleviated hepatic steatosis in methionine and choline deficient L-amino acid diet (MCD) induced non-alcoholic steatohepatitis (NASH) mice. Our data suggest that CAG ameliorates NAFLD via the enhancement of FXR signalling.