Wogonoside preserves against ischemia/reperfusion-induced myocardial injury by suppression of apoptosis, inflammation, and fibrosis via modulating Nrf2/HO-1 pathway

Myocardial ischemia/reperfusion (I/R) injury occurs after restoring blood supply, which brings about extra damage to heart tissue. Thus, exploring protection measures and underlying mechanisms appear to be particularly important. In this study, we investigated the cardioprotection of wogonoside against I/R injury in mice and further uncovered its mechanism.Mice model of myocardial I/R injury was established by left anterior descending coronary artery (LAD). Before modeling, mice were administered the wogonoside (10, 20, and 40 mg/kg) for 7 d. To evaluate the effect of wogonoside through nuclear factor E2-associated factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway, sh-Nrf2 was transfected into wogonoside-treated I/R mice. Subsequently, echocardiography detection, HE staining, western blotting, ELISA, TUNEL assay, and MASSON assay were utilized to evaluate the degree of myocardial injury.In I/R group, mice had severe myocardial injury, however, pretreatment of wogonoside at doses of 20 and 40 mg/kg ameliorated the cardiac function, as evidenced by improving hemodynamic parameters. Besides, wogonoside could relieved the abnormality of cardiomyocytes structure, inflammatory reaction, apoptosis, and myocardial fibrosis. Importantly, wogonoside activated the Nrf2/HO-1 pathway, as demonstrated by increasing Nrf2 expression in nucleus and its downstream genes including HO-1 and NADPH quinone oxidoreductase-1 (NQO1). However, effects of wogonoside on cardioprotection were abolished by sh-Nrf2.Wogonoside exerted the protective role against I/R-induced myocardial injury by suppression of apoptosis, inflammation, and fibrosis via activating Nrf2/HO-1 pathway.