Corilagin alleviates cardiac ischemia-reperfusion injury by inhibiting ferroptosis via PI3K/AKT pathway

Myocardial ischemia-reperfusion (I/R) injury is a significant complication post-revascularization in acute myocardial infarction, with limited effective clinical interventions. Corilagin, a natural polyphenolic compound, exhibits antioxidant and anti-inflammatory properties in various disease models. However, its effects and mechanisms in myocardial I/R injury remain unclear. This study aims to elucidate the specific mechanism by which Corilagin regulates Ferroptosis through the PI3K/Akt signaling pathway, thereby laying a theoretical groundwork for the development of innovative cardioprotective agents. A myocardial I/R model was established in mice through left anterior descending (LAD) artery ligation, and Corilagin's effectiveness was assessed using echocardiography, biochemical assays, and histopathological analysis. Additionally, an in vitro H/R model with neonatal rat cardiomyocytes was employed to examine ferroptosis-related markers, oxidative stress, and mitochondrial function. Utilizing network pharmacology and molecular docking analysis, potential targets were identified and subsequently validated through pharmacological inhibition of the PI3K pathway with LY294002. The findings demonstrate that Corilagin exhibited significant cardioprotective effects against I/R injury, as evidenced by reduced myocardial injury markers, decreased infarct size, and improved cardiac function. In vitro studies revealed that Corilagin treatment enhanced cell viability, reduced ROS levels and iron content, and restored mitochondrial membrane potential. Network pharmacology and molecular docking identified PI3K as a crucial target, with subsequent activation of the PI3K/Akt pathway. Notably, PI3K inhibition abolished Corilagin's suppression of Ferroptosis, underscoring its pathway-dependent action. Corilagin alleviates myocardial I/R injury by activating the PI3K/Akt pathway to suppress Ferroptosis, highlighting its potential as a therapeutic candidate for clinical translation.

Corilagin; Ferroptosis; Myocardial ischemia-reperfusion; PI3K/AKT pathway.