%0 Journal Article
%T Alisol B 23-acetate protects against non-alcoholic steatohepatitis in mice via farnesoid X receptor activation
%A Chang-yuan Wang
%A Hui-jun Sun
%A Jin-yong Peng
%A Peng-yuan Sun
%A Qiang Meng
%A Xiao-kui Huo
%A Xing-ping Duan
%A Zhi-hao Liu
%J Archive of "Acta Pharmacologica Sinica".
%D 2017
%R 10.1038/aps.2016.119
%X Alisol B 23-acetate (AB23A) is a natural triterpenoid isolated from the traditional Chinese medicine rhizoma alismatis, which exhibits a number of pharmacological activities, including anti-hepatitis virus, anti-cancer and antibacterial effects. In this study we examined whether AB23A protected against non-alcoholic steatohepatitis (NASH) in mice, and the mechanisms underlying the protective effects. NASH was induced in mice fed a methionine and choline-deficient (MCD) diet for 4 weeks. The mice were simultaneously treated with AB23A (15, 30, and 60 mg¡¤kg£¿1¡¤d£¿1, ig) for 4 weeks. On the last day, blood samples and livers were collected. Serum liver functional enzymes, inflammatoru markers were assessed. The livers were histologically examined using H&E, Oil Red O, Masson's trichrome and Sirius Red staining. Mouse primary hepatocytes were used for in vitro experiments. The mechanisms underlying AB23A protection were analyzed using siRNA, qRT-PCR, and Western blot assays. AB23A treatment significantly and dose-dependently decreased the elevated levels of serum ALT and AST in MCD diet-fed mice. Furthermore, AB23A treatment significantly reduced hepatic triglyceride accumulation, inflammatory cell infiltration and hepatic fibrosis in the mice. AB23A-induced decreases in serum and hepatic lipids were related to decreased hepatic lipogenesis through decreasing hepatic levels of SREBP-1c, FAS, ACC1 and SCD1 and increased lipid metabolism via inducing PPAR¦Á, CPT1¦Á, ACADS and LPL. The reduction in inflammatory cell infiltration corresponded to deceased serum levels of mKC and MCP-1 and decreased hepatic gene expression of MCP-1 and VCAM-1. The reduction in hepatic fibrosis was correlated with decreased hepatic gene expression of fibrosis markers. The protective effects of AB23A were FXR-dependent, because treatment with the FXR agonist CDCA mimicked AB23A-induced hepato-protection in the mice, whereas co-administration of FXR antagonist guggulsterone abrogated AB23A-induced hepato-protection. In mouse primary hepatocytes, FXR gene silencing abrogated AB23A-induced changes in gene expression of Apo C-II, CPT1¦Á, ACADS and LPL. AB23A produces protective effects against NASH in mice via FXR activation
%K hepatic inflammation
%K non-alcoholic steatohepatitis
%K hepatic fibrosis
%K alisol B 23-acetate
%K farnesoid X receptor
%K CDCA
%K guggulsterone
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220543/