Myocardial ischemia/reperfusion injury (MI/RI) is a life-threatening vascular disease. Salvigenin (SGN) has been reported to play anti-oxidative stress and anti-inflammatory roles in various diseases. Our purpose was to investigate the effect of SGN on MI/RI and its potential mechanism. The viability of hypoxia/reoxygenation (H/R)-induced H9C2 cells was explored by CCK-8 assay. Fe2+ and MDA levels were detected via corresponding commercial kits. The protein expression level was evaluated through western blot. The intracellular ROS level was detected by immunofluorescent staining. IL-1β and IL-18 levels were explored through ELISA assay. C57BL/6 mice were used to construct in vivo model by left anterior descending coronary artery occlusion. The effect of SGN on mice models were evaluated by enzyme activity kits, echocardiography, HE staining and TUNEL. SGN increased the viability of H/R-induced H9C2 cells. SGN reduced the levels of Fe2+ and MDA both in vitro and in vivo. SGN up-regulated SLC7A11, GPX4 and FTH1protein levels and decreased ROS level in H/R-induced H9C2 cells compared with the control cells. SGN down-regulated NLRP3, cleaved caspase-1 and GSDMD-N, and reduced the concentration of IL-1β and IL-18 both in cells and in mice models. Moreover, SGN repaired the left ventricular systolic function, decreased infarct size, serum CK-MB, CTnT, and LDH levels and cardiomyocyte area in mice models. SGN treatment decreased the apoptosis level of myocardial tissue cells. However, co-transfection with the NLRP3 overexpression vector reversed the inhibition of SGN on ferroptosis and pyroptosis. In conclusion, our results indicated that SGN could moderate MI/RI and alleviate ferroptosis and pyroptosis in vitro and in vivo, and its mechanism of action was associated with the inhibition of NLRP3 pathway. SGN may be considered for MI/RI treatment.
Su et al. (Fri,) studied this question.