title: Asperosaponin VI protects cardiac myocytes from hypoxia-induced apoptosis via activation of the PI3K/Akt and CREB pathways.
abstract: 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.
authors.affiliation: School of Pharmacy, Yantai University, Yantai, Shandong, PR China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Li
authors.forename: Jingwei
authors.initials: J
authors.lastname: Tian
authors.forename: Guisheng
authors.initials: G
authors.lastname: Li
authors.forename: Wanglin
authors.initials: W
authors.lastname: Jiang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Xing
authors.forename: Jian
authors.initials: J
authors.lastname: Hou
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhu
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Guanbo
authors.initials: G
authors.lastname: Zhang
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Liu
authors.forename: Zuguang
authors.initials: Z
authors.lastname: Ye
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D003402:Creatine Kinase; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000188:drug therapy; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D012503:Saponins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051017:Apoptosis Regulatory Proteins; D002316:Cardiotonic Agents; D002867:Chromones; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012503:Saponins; C534004:akebia saponin D; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase