Asiatic acid attenuates CCl4-induced liver fibrosis in rats by regulating the PI3K/AKT/mTOR and Bcl-2/Bax signaling pathways

Publication date: July 2018
Source:International Immunopharmacology, Volume 60
Author(s): Liwen Wei, Qingshan Chen, Aijie Guo, Jie Fan, Rong Wang, Hai Zhang
Liver fibrosis is a major pathological feature of chronic liver diseases, and effective therapies are limited at present. Asiatic acid (AA) is a triterpenoid isolated from Centella asiatica, which exhibits efficient anti-inflammatory and anti-oxidative activities. In this study, we attempted to evaluate the potential therapeutic effect of AA on CCl4-induced liver fibrosis in rats and to investigate the underlying molecular mechanisms. Liver fibrosis-related indexes including body weight, biochemical parameters, histological changes, the mRNA expression levels of inflammatory cytokines and biomarkers, and changes in the expression of related proteins in liver tissue were assessed. The results showed that AA treatment effectively ameliorated CCl4-induced liver injury and fibrosis. Mechanistically, AA treatment attenuated CCl4-induced oxidative stress, inflammation, and hepatocyte apoptosis and regulated the Bcl-2/Bax signaling pathway in the liver. Additionally, we demonstrated that AA also inhibited hepatic stellate cell activation and extra cellular matrix (ECM) synthesis by regulating the PI3K/AKT/mTOR signaling pathway. In conclusion, these findings suggest that AA prevents the progression of liver fibrosis through multiple mechanisms and indicate that AA might be used for the treatment of liver fibrosis in the future.

Graphical abstract

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