Aspirin Attenuates Liver Fibrosis via Autophagy Induction.

The aim of the present study was to explore the effect of the non-steroidal anti-inflammatory drugs (NSAID) aspirin on the progression of liver fibrosis and to elucidate its underlying mechanisms, with a specific focus on autophagy. In vitro, the rat hepatic stellate cell line HSC-T6 was activated using transforming growth factor-β1 (TGF-β1). Western blot and real-time PCR analysis were employed to investigate the effect of aspirin on HSC-T6 activation and its association with autophagy levels, including key autophagic markers. In vivo study, liver fibrosis was induced in mice via long-term thioacetamide (TAA) administration. The impact of aspirin on liver fibrosis and function was evaluated using Masson's Trichrome and Sirius Red staining to assess collagen deposition, complemented by serum biochemistry analysis. TGF-β1 treatment inhibited autophagic flux in activated HSC-T6 cells, as evidenced by increased LC3II/I and p62 expression. Notably, aspirin effectively attenuated fibrogenesis in these cells, with significantly lower expression levels of α-SMA and collagen I compared to the TGF-β1-treated control group. Concurrently, aspirin restored autophagy flux as indicated by decreased LC3-II/I and p62 levels, and the effect can be reversed by the autophagy inhibitor chloroquine (CQ). In vivo, aspirin administration markedly attenuated liver fibrosis. Mechanistically, aspirin treatment enhanced autophagic flux, as demonstrated by the accumulation of autolysosomes observed in liver tissues via transmission electron microscopy (TEM). Our study demonstrates that aspirin inhibits liver fibrosis progression by inducing autophagy, highlighting its potential as a therapeutic strategy for liver fibrosis.