Prunasin alleviates OGD/R-induced injury in H9c2 cardiomyocytes via SRC/EGFR-AKT-FoxO-mediated mitochondrial quality control

Background: Myocardial ischemia-reperfusion injury (MIRI) is still difficult to manage clinically, mainly due to limited effective strategies that can simultaneously address oxidative stress, mitochondrial dysfunction and myocardial cell loss. Prunasin is a cyanide glycoside derived from plants of the genus Prunus. Its biological activity has been reported, but its role in ischemia-reperfusion related cardiac injury is not yet clear. Objectives: To evaluate the protective effect of prunasin in an oxygen glucose deprivation/reoxygenation (OGD/R) myocardial cell model and explore its potential mechanism. Methods: Firstly, potential targets and pathways were explored through network pharmacology and molecular docking. Then, functional validation was performed using H9c2 cells subjected to OGD/R. Evaluated cell viability, LDH release, apoptosis, ROS levels, ATP content, mitochondrial membrane potential and key signaling proteins. Results: Network pharmacology highlighted SRC, EGFR and AKT1 as core targets and molecular docking results showed stable binding between prunasin and SRC, supporting this discovery. In experiments, prunasin increased cell viability in a dose-dependent manner and reduced LDH leakage, cell apoptosis and ROS accumulation. Mitochondrial function is also protected, manifested by the recovery of ATP levels and membrane potential. Mechanistically, prunasin activates the SRC/EGFR-AKT-FxO axis, accompanied by enhanced mitochondrial biogenesis, rebalancing of fission/fusion kinetics and increased mitochondrial autophagy, collectively promoting improved mitochondrial quality control under OGD/R stress conditions. Conclusions: Prunasin regulates mitochondrial quality control through the SRC/EGFR-AKT-FxO signaling pathway, thereby reducing OGD/R-induced myocardial cell injury, indicating its potential as a candidate drug for myocardial ischemia-reperfusion intervention.