Mulberry granules protect against diabetic cardiomyopathy through the AMPK/Nrf2 pathway

Mulberry granules (MLD) is a traditional Chinese medicine prescription that has been used in the treatment of diabetes for many years. Recently, we found that MLD protected the heart from diabetes-associated cardiomyopathy when it was used to treat diabetes. However, the beneficial effects and possible mechanism remain unknown. To elucidate these effects, an experimental myocardial ischemia/reperfusion (MI/R) injury model in diabetes rats was used in this study. Male C57BL/6 mice were injected with streptozotocin to induce diabetes. The mice were pretreated with MLD for one month, and then exposed to 30 min of ischemia followed by 24 h of reperfusion. Infarct size, heart function and various cytokines in the heart were assessed. Expression of AMP-activated protein kinase (AMPK) and nuclear factor erythroid 2‑related factor 2 (Nrf2) were investigated by western blotting. In vitro, MLD significantly cleared oxygen-free radicals in DPPH and luminol chemiluminescence models. In vivo, fasting blood glucose, fasting blood insulin and lipids were significantly decreased by MLD. The results showed that MLD improved the cardiac function and decreased myocardial infarct size in the diabetic mice subjected to MI/R. In addition, upon pretreatment with MLD before MI/R treatment, GSH, SOD, CAT and GR were significantly increased in a dose-dependent manner. Pretreatment with MLD also significantly induced the expression of Nrf2, and the cardioprotective effects of MLD were abolished in Nrf2-knockout mice. Furthermore, we also found that AMPK increase is upstream and was required for Nrf2 activation mediated by MLD. In conclusion, MLD protects against diabetic-associated cardiomyopathy by suppressing oxidative stress induced by hyperglycemia and MI/R through the AMPK/Nrf2 signaling pathway.