Delphinidin inhibits the ALOX15-mediated ferroptosis in rats to alleviate myocardial ischemia and reperfusion injury.

OBJECTIVE

The present study aimed to investigate the role of delphinidin (Dp) in myocardial ischemia-reperfusion injury (MIRI) and elucidate the underlying mechanism.

METHODS

MIRI animal models were established in Sprague-Dawley rats by ligation of left anterior descending coronary artery (LAD) ligation for 30 min and reperfusion of 2 h. Primary cardiomyocytes and H9C2 cells were stimulated by oxygen-glucose deprivation/regain (OGD/R) conditions for mimicking MIRI cell models. Ultrasound, hematoxylin and eosin and Masson staining were used to evaluate cardiac function and myocardial infarction in rats following Dp treatment. Cell counting kit-8 assay and flow cytometry were performed to detect cell viability and apoptosis, respectively. Western blotting and quantitative real-time polymerase chain reaction measured ALOX15 expression. Additionally, ferroptosis-related factors and lactate dehydrogenase levels were detected using commercial kits.

RESULTS

In MIRI rats, Dp treatment dose-dependently increased the left ventricular ejection fraction (EF) and fractional shortening (FS) while reduced the left ventricular internal diameter in diastole (LVIDd) and systole (LVIDs). The increase of necrosis and fibrosis in cardiac tissues of MIRI rats were relieved by Dp. Dp treatment inhibited the apoptosis and ferroptosis of cardiomyocytes both in vivo and in vitro. Mechanically, Dp docked with a ferroptosis-related protein ALOX15 to induce its degradation. Moreover, ferroptosis activator erastin and ALOX15 overexpression reversed the protective effects of Dp on cardiomyocytes.

CONCLUSION

Dp inhibited ferroptosis by molecular docking ALOX15 and inducing its degradation, thereby improving MIRI.