Syringin exerts anti‐inflammatory and antioxidant effects by regulating SIRT1 signaling in rat and cell models of acute myocardial infarction

INTRODUCTION: This study aimed to investigate the role of syringin in improving heart function during myocardial ischemia/reperfusion (I/R) and to determine whether the sirtuin 1/peroxisome proliferator‐activated receptor gamma coactivator 1 alpha (SIRT1/PGC‐1α) pathway contributes to this cardioprotective effect in vivo and in vitro. METHODS: H9c2 cells were incubated with H(2)O(2) for 12 h. The effect of syringin was assessed by measuring cell viability; the apoptotic rate; Keap1/NRF2/HO‐1 activation; and the levels of proinflammatory cytokines, oxidative products, and antioxidative enzymes. In addition, SIRT1 was silenced via short hairpin RNA (shRNA)‐SIRT1 transfection to evaluate its involvement in syringin‐mediated protection. Syringin rescued cells from H(2)O(2)‐induced reductions in viability, antioxidative enzyme levels, and NRF2/HO‐1 activation; likewise, syringin inhibited apoptosis, inflammation, and oxidative stress. We also created a rat model of I/R by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 12 min. Syringin was then intraperitoneally injected, and the effect on infarct size and cardiac function was examined after 7 days. NRF2/HO‐1 activity and the levels of myocardial proinflammatory cytokines, oxidative products, and antioxidative enzymes were measured. RESULTS: In comparison to the untreated I/R group, the syringin treatment group exhibited improved cardiac function and reduced cardiac lesion and infarct size. Syringin administration also markedly reduced the levels of proinflammatory cytokines and reactive oxygen species and promoted antioxidative enzyme expression and NRF2/HO‐1 pathway activation. CONCLUSIONS: Syringin may serve a protective role in animal and cell models of I/R by improving cardiac function, inhibiting the inflammatory response, and activating the antioxidative response.