Astragalin promotes HSCs ferroptosis through NCOA4 mediated ferritinophagy to alleviate liver fibrosis in zebrafish and mice.

Liver fibrosis is pathological progression of chronic liver disease. Recent research has focused on the activation of hepatic stellate cells (HSCs), highlighting their potential as targets for mitigating fibrosis. While herbal medicines and natural active ingredients have shown promising anti-fibrotic effects in clinical treatments, the impact of Astragalin (Ag) remains unexplored. In this study, we established in vivo and in vitro studies, employing fluorescence probe staining, transmission electron microscopy, and various analytical techniques. The results demonstrated Ag operates within a wide range of safe therapeutic doses in zebrafish and effectively alleviates liver fibrosis. Further experiments demonstrated that Ag induced HSCs ferroptosis via this pathway, leading to iron overload and ultimately alleviating liver fibrosis. In general, this study demonstrated that Ag promotes HSCs ferroptosis through NCOA4-mediated ferritinophagy, clarifying its mechanism in treating liver fibrosis and positioning Ag as a promising candidate for future clinical interventions.