Quercetin improves diabetic cardiomyopathy by inhibiting pyroptosis via the Nrf2 pathway

Introduction: The aim of the study was to investigate whether quercetin can promote the translocation of Nuclear factor erythroid-2 related factor 2 (Nrf2) into the nucleus to inhibit pyroptosis progression and improve diabetic cardiomyopathy. Research design and methods:The protective effect of quercetin against diabetic cardiomyopathy was evaluated using a diabetic rat model by analyzing the expression of pyroptosis pathway proteins, myocardial cell apoptosis rate, degree of myocardial fibrosis, and serum inflammatory indexes in the hearts of rats in each group. The expression of Nrf2 in the nucleus of myocardial tissue and H9C2 cells were analyzed to clarify the role of quercetin in promoting the translocation of Nrf2 into the nucleus. In addition, the Nrf2 inhibitor ml385 was co-incubated with the myocardial tissue to confirm that quercetin inhibits diabetes-induced cardiomyocyte pyroptosis via the Nrf2 pathway. Results: Quercetin promoted the translocation of Nrf2 into the nucleus in the cardiac cells of diabetic rats, increased the expression of antioxidant proteins HO-1, GCLC, and SOD, reduced the accumulation of ROS and the level of cell apoptosis in diabetic cardiomyocytes, and alleviated the cardiac fibrosis caused by diabetes. The therapeutic effects of quercetin were further validated in H9C2 cardiomyocytes. Additionally, ml385 prevented the beneficial effects of quercetin on diabetic cardiomyopathy, further indicating that the inhibition of pyroptosis by quercetin requires the participation of the Nrf2 pathway. Conclusions: Quercetin promotes the translocation of Nrf2 into the nucleus, increases the expression of antioxidant factors in cells, and inhibits the progression of cell pyroptosis thereby alleviating diabetic cardiomyopathy.