Ginkgo biloba Pretreatment Attenuates Myocardial Ischemia-Reperfusion Injury via mitoBKCa

Abstract

Ginkgo biloba extracts (EGb) alleviate myocardial ischemia/reperfusion (MI/R) injury. However, the underlying mechanisms have not yet been characterized. This study aimed to investigate whether activation of large-conductance ${\text{Ca}}^{2+}$-activated ${\text{K}}^{+}$ channels at the inner mitochondrial membrane (${\text{mitoBK}}_{\text{Ca}})$ of cardiomyocytes is involved in Ginkgo biloba extract-mediated cardioprotection. Shuxuening injection (SXNI, 12.5$$ml/kg/d), a widely prescribed herbal medicine containing Ginkgo biloba extracts in China, or vehicle, was administered to C57BL/6 mice via tail vein injection for one week prior to surgical procedures. The mitoBK_Ca blocker paxilline (PAX) (1$$ml/kg, 115 nM) was administered via tail vein injection 30$$min prior to the onset of ischemia. The mice were randomly divided into the following groups: Sham, MI/R, MI/R+SXNI, and MI/R+SXNI+PAX. MI/R was induced by ligating the left anterior descending coronary artery for 30$$min with subsequent reperfusion for 24$$h. SXNI pretreatment conferred cardioprotective effects against MI/R injury as evidenced by reduced infarct size, improved cardiac function, and improved mitochondrial function. However, these effects were abrogated by co-administration with PAX. In addition, activation of mitoBK_Ca by Ginkgo biloba extract EGb761 reduced hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury in vitro through the inhibition of mitochondrial fragmentation, restoration of the mitochondrial membrane potential, decreased generation of superoxide, and inhibition of apoptosis which is associated with alleviating mitochondrial ${\text{Ca}}^{2+}$ overload. These results indicated that Ginkgo biloba extracts pretreatment protected against MI/R injury via activation of mitoBK_Ca.

Keywords: Extracts; Cardioprotection; Myocardial Ischemia/Reperfusion; mitoBK.