Berberine Ameliorates Diabetic Cardiomyopathy in Mice by Decreasing Cardiomyocyte Apoptosis and Oxidative Stress

Background: Diabetic cardiomyopathy is a multifaceted complication of diabetes that lacks effective treatments. Berberine (BBR), a bioactive compound from Rhizoma coptidis , has potential therapeutic implications, but its precise role in diabetic cardiomyopathy remains to be defined. Methods: In this study, a diabetic cardiomyopathy model was established by administration of a high-fat diet and streptozotocin injection to C57BL/6J mice. Concurrently, the mice received BBR treatment daily for a duration of 8 weeks. After the treatment period, myocardial injury, cardiac function, and the levels of oxidative stress and apoptosis were assessed. Results: BBR significantly ameliorated cardiac dysfunction and histopathological damage caused by diabetic cardiomyopathy. This treatment also elevated serum superoxide dismutase levels while decreasing malondialdehyde levels. The anti-apoptotic activity of BBR was evidenced by a decrease in TUNEL-positive cells and the percentage of apoptotic cells, as determined by flow cytometry, in conjunction with diminished levels of BCL2-associated X protein/B cell lymphoma 2 (BAX/BCL2) in heart tissues. Mechanistically, BBR was found to ameliorate diabetic cardiomyopathy by upregulating the expression of myocardial methionine sulfoxide reductase A (MsrA) and concurrently suppressing cardiac CaMKII oxidation. Conclusions: BBR alleviates diabetic cardiomyopathy by inhibiting myocardial apoptosis and oxidative stress through the MsrA and CaMKII signaling pathways.