Protective effects of liriodendrin on myocardial infarction-induced fibrosis in rats via the PI3K/Akt autophagy pathway: A network pharmacology study.

Abstract

Liriodendrin (LIR) has been reported to improve cardiac function in rats following myocardial infarction. However, its role and mechanism in reparative myocardial fibrosis remain unclear. In this study, a rat model of myocardial fibrosis was established via left anterior descending artery ligation and randomly divided into three groups (n = 6 per group): sham-operated, myocardial infarction, and LIR intervention (100 mg/kg/day) groups. The pharmacological effects of LIR were assessed using echocardiography, hematoxylin, and eosin (H&E) staining, and Masson staining. Network pharmacology and bioinformatics were utilized to identify potential mechanisms of LIR, which were further validated via western blot analysis. Our findings demonstrated that LIR improved cardiac function, histology scores, and collagen volume fraction. Moreover, LIR downregulated the expression of Beclin-1, LC3-II, and LC3-I while upregulating the expression of p62, indicating LIR-activated autophagy in the heart after myocardial infarction. Further analysis revealed that the PI3K/Akt signaling pathway was significantly enriched and validated by western blot. This analysis suggested that the ratios of p-PI3K/PI3K, p Akt/Akt, and p-mTOR/mTOR were significantly increased. LIR may attenuate myocardial infarction-induced fibrosis in rats by inhibiting excessive myocardial autophagy, with the potential mechanism involving the activation of the PI3K/Akt/mTOR pathway.