title: Methylophiopogonanone A suppresses ischemia/reperfusion-induced myocardial apoptosis in mice via activating PI3K/Akt/eNOS signaling pathway.
abstract: OBJECTIVE
  The dried tuber root of Ophiopogon japonicus 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 Ophiopogon japonicus, on myocardial ischemia/reperfusion (I/R) injury.
  
  
  METHODS
  Mice were pretreated with MO-A (10 mg·kg(-1)·d(-1), 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 μmol/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).
  
  
  CONCLUSIONS
  MO-A attenuates I/R-induced myocardial apoptosis in mice via activating the PI3K/Akt/eNOS signaling pathway.
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
authors.forename: Fei
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
authors.forename: Bang-Long
authors.initials: BL
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
authors.forename: Hong-Jing
authors.initials: HJ
authors.lastname: Jia
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
authors.forename: Ji-Xiong
authors.initials: JX
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
authors.forename: Jian-Long
authors.initials: JL
authors.lastname: Sheng
authors.affiliation: School of Nursing, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: School of Nursing, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D052117:Benzodioxoles / Q000737:chemistry / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000737:chemistry / Q000627:therapeutic use*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D007529:Isoflavones / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D031441:Ophiopogon / Q000737:chemistry; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D052117:Benzodioxoles; D002316:Cardiotonic Agents; D007529:Isoflavones; C543188:methylophiopogonanone A; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt