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

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• 作者：Chunmei Li ; Jingwei Tian ; Guisheng Li ; Wanglin Jiang ; Yanli Xing ; Jian Hou ; Haibo Zhu ; Hong Xu ; Guanbo Zhang ; Zhifeng Liu ; Zuguang Ye
• 关键词：Asperosaponin VI ; Cardiomyocyte apoptosis ; Phosphatidylinositol-3-kinase (PI3K)/Akt ; CREB ; Bcl-2/Bax ; Caspase-3
• 刊名：European Journal of Pharmacology
• 出版年：2010
• 出版时间：15 December 2010
• 年：2010
• 卷：649
• 期：1-3
• 页码：100-107
• 全文大小：3614 K

文摘

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 as 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.