A new flavonoid glycoside (APG) isolated from Clematis tangutica attenuates myocardial ischemia/reperfusion injury via activating PKCε signaling

Abstract Clematis tangutica has been shown to be beneficial for the heart; however, the mechanism of this effectremains unknown. Apigenin-7-O-β-D-(-6″-p-coumaroyl)-glucopyranoside (APG) is a new flavonoid glycoside isolated from Clematis tangutica . This study investigates the effects of APG on myocardial ischemia/reperfusion (IR) injury (IRI). An IRI model of primary myocardial cells and mice was used in this study. Compared with the IR group, APG preconditioning is protective against IRI in primary myocardial cells and in mice hearts in a dose-dependent manner. The cardioprotective mechanisms of APG may involve a significant PKCe translocation into the mitochondria and an activation of the Nrf2/HO-1 pathway, which respectively suppressesmitochondrial oxidative stress and inhibits apoptosis. In addition, PKCe-targeted siRNA and a PKCe specialized inhibitor (e-V1-2) were used to inhibit PKCe expression and activity. The inhibition of PKCe reversed the cardioprotective effect of APG, with an inhibition of Nrf2/HO-1 activation and increased mitochondrial oxidative stress and cardiomyocyte apoptosis. In conclusion, PKCe activation plays an important role in the cardioprotective effects of APG. PKCe activation induced by APG preconditioning reduces mitochondrial oxidative stress and promotes Nrf2/HO-1-mediated anti-apoptosis signaling.