Effects of berbamine against myocardial ischemia/reperfusion injury: Activation of the 5' adenosine <scp>monophosphate‐activated</scp> protein kinase/nuclear factor erythroid <scp>2‐related</scp> factor pathway and changes in the mitochondrial state

This study was designed to investigate whether berbamine (BA)-induced cardioprotective effects were related to 50 adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor (Nrf2) signaling and changes in the mitochondria in myocardial ischemia/reperfusion (I/R) injury. C57/BL6 mice were exposed to BA (10 mg/kg/d), with or without administration of the AMPK specific inhibitor compound C (5 mg/kg/d) or the Nrf2 specific inhibitor ML-385 (30 mg/kg/d), and then subjected to a myocardial I/R operation. As expected, BA significantly improved post-ischemic cardiac function, reduced infarct size and apoptotic cell death, decreased oxidative stress, and improved the mitochondrial state. Furthermore, BA markedly increased AMPK activation, Nrf2 nuclear translocation, and the levels of NAD(P)H quinone dehydrogenase and heme oxygenase-1. Nevertheless, these BA-induced changes were abrogated by compound C. In addition, ML-385 also canceled the cardioprotective effects of BA but had little effect on AMPK activation. Our results demonstrate that BA alleviates myocardial I/R injury and the mitochondrial state by inhibiting apoptosis and oxidative stress via the AMPK/Nrf2 signaling pathway.