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Pharmacol Res. 2017 Jul;121:22-32. doi: 10.1016/j.phrs.2017.04.021. Epub 2017 Apr 18.

Cycloastragenol improves hepatic steatosis by activating farnesoid X receptor signalling.

Author information

1
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
2
School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai, China.
3
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Brown Foundation Institute of Molecular Medicine and Program in Neuroscience, Graduate School of Biological Sciences, University of Texas McGovern Medical School, Houston, TX, USA.
4
Research Center for Traditional Chinese Medicine of Complexity Systems, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
5
Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: jiliver@vip.sina.com.
6
Brown Foundation Institute of Molecular Medicine and Program in Neuroscience, Graduate School of Biological Sciences, University of Texas McGovern Medical School, Houston, TX, USA. Electronic address: Qingchun.Tong@uth.tmc.edu.
7
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: chuang@shutcm.edu.cn.

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.

KEYWORDS:

Cycloastragenol; Farnesyl X receptor; Metabolic syndrome; Non-alcoholic fatty liver disease

PMID:
28428116
DOI:
10.1016/j.phrs.2017.04.021
[Indexed for MEDLINE]

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