4.7 Article

Rotundic acid ameliorates non-alcoholic steatohepatitis via SREBP-1c/ SCD1 signaling pathway and modulating gut microbiota

Journal

INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 99, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.intimp.2021.108065

Keywords

NASH; RA; SCD1; SREBP-1c; Gut microbiota; SCFA

Funding

  1. Department of Natural Resources of Guangdong Province, China [GDNRC [2020] 033]
  2. State Key Laboratory of Anti-Infective Drug Development [SKLAID202001]

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The study evaluated the pharmacological effect and action mechanism of Rotundic acid extracted from Ilex rotunda Thunb on non-alcoholic steatohepatitis (NASH). Results showed that RA significantly reduced serum LDL levels, hepatic lipid content, and improved liver inflammation, while enhancing the recovery of gut microbiota and short-chain fatty acids.
Non-alcoholic steatohepatitis (NASH) is a devastating form of non-alcoholic fatty liver disease (NAFLD) with distinguished hallmarks of steatosis and inflammation. Rotundic acid (RA) is a natural pentacyclic triterpene compound extracted from the bank of Ilex rotunda Thunb with a wide range of biological activities. The aim of the study is to evaluate the pharmacological effect and action mechanism of RA on NASH in vitro and in vivo. RA has weak lipid lowering ability in rat primary hepatocytes, significantly decreases serum LDL level, hepatic TG and TC levels and lipid droplets, reduces NAS compared with the NASH group, and alleviates hepatic inflammation. RA also enhances the recovery of intestinal bacterial community and intestinal-derived short-chain fatty acid caused by high food diet (HFD). Further investigation shows that RA protects against HFD-induced NASH via downregulating the expression of SREBP-1c/SCD1 signaling pathway and improving gut microbiota. These findings imply that RA might be helpful for the alleviation of NASH.

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