Asperosaponin VI protects cardiac myocytes from hypoxia-induced apoptosis via activation of the PI3K/Akt and CREB pathways

Cardiomyocyte apoptosis plays a critical role in the progress of heart diseases Asperosaponin VI (ASA VI) a triterpene saponin isolated from Dipsacus asper Wall has shown cardioprotective effects in vivo However whether ASA VI has a protective effect against cardiomyocyte apoptosis is poorly understood The present study was aimed to investigate the cardioprotective role of ASA VI and the underlying mechanisms in hypoxia-induced cardiomyocyte apoptosis Cardiomyocytes were exposed to hypoxic condition for 6 h and then cell viability markedly decreased lactate dehydrogenase (LDH) and creatine phosphokinase (CK) activities in the culture supernatant significantly increased Hypoxia-activated apoptosis were confirmed by Hoechst 33258 nuclear staining and Annexin V-FITC staining These changes were associated with the decrease of the Bcl-2/Bax ratio active caspase 3 expression phosphorylations of Akt and cAMP response element-binding protein (CREB) Moreover ASA VI significantly attenuated increased LDH and CK activities and increased cell viability in hypoxia treated myocytes in a dose-dependent fashion Hoechst 33258 nuclear staining and Annexin V-FITC staining observations demonstrated the same protective effects ASA VI treatment inhibited apoptosis in hypoxia-induced cardiomyocyte by increasing the Bcl 2/Bax ratio and decreasing active caspase 3 expression as well enhancing of p Akt and p-CREB Furthermore the protective effects of ASA VI were prevented by phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 treatment In consequence we demonstrated that ASA VI had protective effect against hypoxia induced cardiomyocytes apoptosis probably by activating the PI3K/Akt and CREB pathways (C) 2010 Elsevier B V All rights reserved