Journal Article

Gypenoside XIII regulates lipid metabolism in HepG2 hepatocytes and ameliorates nonalcoholic steatohepatitis in mice

Chen, Li‐Chen, Liou, Chian‐Jiun, Cheng, Shu‐Chen, Huang, Wen‐Chung, Yeh, Kuo‐Wei, Wu, Ya‐Xuan

2024

Overview

Gypenoside XIII is isolated from Gynostemma pentaphyllum (Thunb.) Makino. In mice, G. pentaphyllum extract and gypenoside LXXV have been shown to improve non‐alcoholic steatohepatitis (NASH). This study investigated whether gypenoside XIII can regulate lipid accumulation in fatty liver cells or attenuate NASH in mice. We used HepG2 hepatocytes to establish a fatty liver cell model using 0.5 mM oleic acid. Fatty liver cells were treated with different concentrations of gypenoside XIII to evaluate the molecular mechanisms of lipid metabolism. In addition, a methionine/choline‐deficient diet induced NASH in C57BL/6 mice, which were given 10 mg/kg gypenoside XIII by intraperitoneal injection. In fatty liver cells, gypenoside XIII effectively suppressed lipid accumulation and lipid peroxidation. Furthermore, gypenoside XIII significantly increased SIRT1 and AMPK phosphorylation to decrease acetyl‐CoA carboxylase phosphorylation, reducing fatty acid synthesis activity. Gypenoside XIII also decreased lipogenesis by suppressing sterol regulatory element‐binding protein 1c and fatty acid synthase production. Gypenoside XIII also increased lipolysis and fatty acid β‐oxidation by promoting adipose triglyceride lipase and carnitine palmitoyltransferase 1, respectively. In an animal model of NASH, gypenoside XIII effectively decreased the lipid vacuole size and number and reduced liver fibrosis and inflammation. These findings suggest that gypenoside XIII can regulate lipid metabolism in fatty liver cells and improve liver fibrosis in NASH mice. Therefore, gypenoside XIII has potential as a novel agent for the treatment of NASH.

• Publisher: Wiley Publishing Asia Pty Ltd,John Wiley & Sons, Inc,Wiley
• Subject: Analysis / Animals / Antibodies / Care and treatment / Complications and side effects / Decomposition / Diet / Fatty acids / Fatty Acids - metabolism / Fatty Acids - pharmacology / Fatty liver / Gynostemma - chemistry / Gynostemma - metabolism / gypenoside XIII / Health aspects / Hepatocytes - metabolism / Inflammation / Kinases / Laboratory animals / Lipid Metabolism / Lipid peroxidation / Lipids / Lipids - pharmacology / lipogenesis / lipolysis / Liver - metabolism / Liver cells / Liver cirrhosis / Liver Cirrhosis - metabolism / Metabolism / Mice / Mice, Inbred C57BL / Non-alcoholic Fatty Liver Disease - drug therapy / Non-alcoholic Fatty Liver Disease - metabolism / non‐alcoholic steatohepatitis / Original / Oxidation / Oxidative stress / Phosphorylation / Plant Extracts / Proteins / Synthesis / Triglycerides