Erianin ameliorates liver fibrosis through the PRDX3/NLRX1 axis.

Liver fibrosis constitutes a central pathological hallmark of advanced chronic liver diseases. However, effective therapeutic targets and pharmacological interventions remain insufficiently defined. Mitochondrial oxidative stress plays a pivotal role in the pathogenesis of hepatic stellate cells (HSCs) activation during liver fibrosis. While erianin, a natural bibenzyl compound extracted from the stems of Dendrobium chrysotoxum Lindl., exerts antioxidant effects in various diseases, its protective effect against liver fibrosis remains elusive. Thus, this study aimed to evaluate the therapeutic potential of erianin against liver fibrosis and to explore the underlying molecular mechanisms. The results revealed that erianin markedly attenuated CCl4-and TGF-β1-induced HSCs activation and liver fibrosis. Molecular docking analyses identified PRDX3 as a specific binding target of erianin, with a subsequent increase in PRDX3 expression. However, PRDX3 knockdown abolished the protective effects of erianin on liver fibrosis. Mechanistically, RNA-seq and molecular assays demonstrated that PRDX3 alleviated liver fibrosis by activating NLRX1 and that erianin mediated its protection through the PRDX3/NLRX1 pathway. Collectively, these findings demonstrate that erianin alleviates liver fibrosis via the PRDX3/NLRX1 axis.