Puerarin alleviates myocardial ischemia-reperfusion injury by enhancing FUNDC1-mediated mitophagy.

Myocardial ischemia‑reperfusion injury (I/R) is a major contributor to adverse outcomes in ischemic heart disease. Mitochondrial dysfunction plays a central role in I/R, and modulating mitophagy has shown potential in attenuating such injury. Nevertheless, whether puerarin influences mitophagy during I/R remains poorly understood. An in vivo I/R (30 min/24 h) model was established in C57BL/6 mice after 7 day puerarin pretreatment. In vitro, a hypoxia‑reoxygenation H/R (8 h/4 h) model was constructed using H9c2 cardiomyocytes. Cardiac function was assessed by echocardiography, infarct size was determined via Evans Blue‑TTC staining, mitophagy was visualized by transmission electron microscopy, and expression of mitophagy‑related proteins was evaluated by western blot. Puerarin significantly reduced I/R‑induced damage in both models. It attenuated mitochondrial depolarization and reactive oxygen species generation, increased mitophagic activity, and upregulated the mitophagy receptor FUNDC1. Puerarin alleviates myocardial ischemia‑reperfusion injury by enhancing FUNDC1‑mediated mitophagy, particularly during early reperfusion. These results reveal a key mechanism underlying the cardioprotective effect of puerarin and support its further development as a therapeutic agent for I/R.