Hederagenin ameliorates CCl₄-induced liver fibrosis and HSCs activation by inhibiting mitophagy via PINK1/Parkin pathway

Liver fibrosis is a key pathological characteristic of chronic liver diseases and currently lacks effective treatment. In recent years, increasing number of researches have proved that Hederagenin possesses diverse pharmacological activities, including anti-inflammatory and hepatoprotective effects. However, its anti-fibrotic activity and the underlying molecular mechanisms in liver fibrosis remain incompletely understood. In this study, we investigated the anti-fibrotic effects of Hederagenin and its underlying mechanisms in liver fibrosis, with a particular focus on the PINK1/Parkin-mediated mitophagy pathway. Using CCl4‐induced liver fibrosis mouse models and TGF-β1-induced LX‐2 cells models, we demonstrate that Hederagenin effectively ameliorated liver injury, reduced collagen deposition, and improved mitochondrial structure by through suppressing PINK1/Parkin-mediated mitophagy pathway. In vitro, experiments further confirmed that the Hederagenin inhibited the activation of TGF-β1-induced LX-2 cells through regulation of PINK1/Parkin-dependent mitophagy. These findings reveal a novel mechanism by which Hederagenin attenuates liver fibrosis and highlight its potential as a promising therapeutic agent for the treatment of liver fibrosis.