Abstract
Agrimonia pilosa Ledeb. (APL) is an edible and medicinal plant, which has a favorable cardioprotective effect. Myocardial fibrosis (MF) is a hallmark pathological feature of various cardiovascular diseases. This study aims to evaluate its protective effects against isoproterenol (ISO)-induced MF and investigate the underlying mechanisms. HPLC was employed to analyze the main active ingredients in APL. Network pharmacology methods, combined with experimental validation, elucidated the mechanism by which APL modulates mitophagy to alleviate MF. HPLC analysis showed that six ingredients were identified. We demonstrated that APL significantly attenuated myocardial injury, enhanced cardiac function, inhibited oxidative stress and apoptosis, and effectively ameliorated MF progression. Network pharmacological predictions and in vivo experimental validation demonstrated that APL exerts its therapeutic effects through regulation of the FOXO signaling pathway and suppression of excessive mitophagy. Furthermore, we artificially elevated FOXO1 expression in vitro, which reversed the effects of APL, as evidenced by increased expression of mitophagy and fibrosis-related proteins. Consistent results from both in vivo and in vitro experiments demonstrated that APL attenuates ISO-induced MF and suppresses mitophagy mediated by the FOXO signaling pathway.