Methylophiopogonanone A suppresses ischemia/ reperfusion-induced myocardial apoptosis in mice via activating PI3K/Akt/eNOS signaling pathway

• Published in: Acta pharmacologica Sinica Vol. 37; no. 6; pp. 763 - 771
• Main Authors: He, Fei, Xu, Bang-long, Chen, Cai, Jia, Hong-jing, Wu, Ji-xiong, Wang, Xiao-chen, Sheng, Jian-long, Huang, Li, Cheng, Jing
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2016; Nature Publishing Group
• Subjects: Animals; Apoptosis - drug effects; Benzodioxoles - chemistry; Benzodioxoles - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cardiotonic Agents - chemistry; Cardiotonic Agents - therapeutic use; caspase-3; Cell Line; Enzyme Activation - drug effects; Heart - drug effects; Immunology; Internal Medicine; Isoflavones - chemistry; Isoflavones - therapeutic use; Male; Medical Microbiology; Mice; Mice, Inbred C57BL; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardium - metabolism; Myocardium - pathology; Nitric Oxide Synthase Type III - metabolism; Ophiopogon - chemistry; Original; original-article; Pharmacology/Toxicology; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Rats; Signal Transduction - drug effects; Vaccine; 信号通路; 心肌细胞凋亡; 激活; 缺血再灌注; 诱导; 麦冬; 黄烷酮; ischemia/reperfusion; wortmannin; eNOS; methylophiopogonanone A; H9C2 rat cardiomyocytes; cardio-protection; apoptosis; coronary heart disease; PI3K/Akt
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2016.14

Aim： The dried tuber root of Ophiopogonjaponicus has been used in the traditional Chinese medicine for treatment of myocardial ischemia and thrombosis. In this study we investigated the effects of methylophiopogonanone A （MO-A）, a major homoisoflavonoid in Ophiopogonjaponicus, on myocardial ischemia/reperfusion （I/R）injury. Methods： Mice were pretreated with MO-A （10 mg.kg-l.d1, po） for 2 weeks and then subjected to transient occlusion of the left anterior descending coronary artery. Cardiac function was evaluated, and the infarct size and apoptosis index were assessed. The mechanisms underlying the cardio-protection of MO-A were analyzed in H9C2 rat cardiomyocytes subjected to hypoxia/reoxygenation （H/R）. The cell viability and apoptosis were evaluated; apoptotic and relevant signaling proteins were analyzed. NO levels in the culture medium were assessed. Results： In I/R mice, pretreatment with MO-A significantly reduced the infarct size （by 60.7%） and myocardial apoptosis （by 56.8%）, and improved cardiac function. In H9C2 cells subjected to H/R, pretreatment with MO-A （10 pmol/L） significantly decreased apoptosis and cleaved caspase-3 expression, elevated the Bcl-2/Bax ratio and restored NO production. Furthermore, pretreatment with MO-A markedly increased the activation of PI3K/Akt/eNOS pathway in H9C2 cells subjected to H/R, and the protective effects of MO-A were abolished in the presence of the PI3K inhibitor wortmannin （100 nmol/L）. Conclusion： MO-A attenuates I/R-induced myocardial apoptosis in mice via activating the PI3K/Akt/eNOS signaling pathway.