摘要

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. Glaucocalyxin A (GLA) is a diterpenoid compound that possesses various activities. In the study, we explored the effect of GLA on high fat diet (HFD)-induced fatty liver and fibrosis. We showed that GLA significantly inhibited hepatic steatosis and decreased the hepatic level of triglyceride and total cholesterol and serum level of alanine aminotransferase and aspartate aminotransferase in HFD-fed mice. GLA significantly inhibited the increase of hydroxyproline, mRNA expression of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta 1 (TGF beta 1) induced by HFD in vivo and PA in vitro. Moreover, GLA decreased the level of proinflammatory cytokines in livers of HFD-fed mice and PA-treated hepatocytes. Decrease of sirtuin 1 (SIRT1) expression induced by HFD and PA was inhibited by GLA. Furthermore, knockdown of SIRT1 suppressed the inhibitory effect of GLA on lipid accumulation, inflammation and fibrosis-biomarkers. The data in our study showed that GLA protected against fatty liver, inflammation and fibrosis. Upregulation of SIRT1 was responsible for GLA-induced inhibition of lipid accumulation, inflammation and fibrogenesis. Overall, our study demonstrated that GLA may be a promising choice for the therapy of fatty liver and fibrosis.