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

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 eval...

Full description

Saved in:
Bibliographic Details
Published in:International immunopharmacology 2018-07, Vol.60, p.1-8
Main Authors: Wei, Liwen, Chen, Qingshan, Guo, Aijie, Fan, Jie, Wang, Rong, Zhang, Hai
Format: Article
Language:English
Subjects:
AKT/mTOR
Asiatic acid
Bcl-2/Bax
Liver fibrosis
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. [Display omitted] •Asiatic acid (AA) attenuated CCl4-induced liver injury and fibrosis in rats.•AA mitigated oxidative stress and inflammation in CCl4-induced liver fibrosis.•AA regulated Bcl-2/Bax signaling pathway to inhibit CCl4-induced apoptosis.•AA inhibited PI3K/AKT/mTOR signaling pathway to inhibit hepatic stellate cell activation and ECM synthesis.
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2018.04.016