Roles of berbamine in the normal and ischemia/reperfusion hearts

Myocardial infarction resulting from coronary atherosclerosis is the leading cause of death in modern soci- ety. Reperfusion is an essential treatment to salvage ischemia myocardium from necrosis, while it also leads to addi- tional damage. Therefore, exploring effective medicines to protect the heart from post-ischemic injury is one of the major objectives of cardiovascular research. Berbamine is a nature compound of bisbenzylisochinoline alkaloids from Barberry. We found that it displays positive inotropic and lusitropic effects at lower concentrations by increasing myofilament Ca2＋ sensitivity via a PKCe-dependent signaling pathway. Moreover, berbamine preconditioning con- fers cardioprotection against ischemia/reperfusion （I/R） injury by attenuating the Ca2＋ overloading and preventing the calpain activation through the activating of PI3K-Akt-GSK3β pathway and subsequently opening of the mitoKATP channel. Furthermore, we demonstrate that berbamine postconditioning conferred the cardioprotective effect against I/R injury by the regulation of autophagy. These findings reveal new roles and mechanisms of berbamine in the heart and cardioprotection against I/R injury.