title: Luteolin inhibits ROS-activated MAPK pathway in myocardial ischemia/reperfusion injury.
abstract: OBJECTIVE
  Luteolin is a falconoid compound that has an antioxidant effect, but its contribution to ROS-activated MAPK pathways in ischemia/reperfusion injury is seldom reported. Here, we have confirmed that it exhibits an antioxidant effect in myocardial ischemia/reperfusion injury (MIRI) by inhibiting ROS-activated MAPK pathways.
  
  
  METHODS
  We exposed rat hearts into the left anterior descending coronary artery (LAD) ligation for 30min followed by 1h of reperfusion. Observations were carried out using electrocardiography; detection of hemodynamic parameters; and testing levels of lactate dehydrogenase (LDH), creatine kinase (CK), total superoxide dismutase (T-SOD), and malondialdehyde (MDA). Mitogen-activated protein kinase (MAPK) pathway was measured by western blot and transmission electron microscopy was applied to observe the myocardial ultrastructure. Rat H9c2 cell in 95% N2 and 5% CO2 stimulated the MIRI. Oxidation system mRNA levels were measured by real-time PCR; mitochondrial membrane potential and apoptosis were measured by confocal microscopy and flow cytometry; western blot analysis was used to assay caspase-3, -8, and -9 and MAPK pathway protein expression; the MAPK pathway was inhibited using SB203580 (p38 MAPK inhibitor) and SP600125 (c-Jun NH2-terminal kinase inhibitor) before H9c2 cells were exposed to hypoxia/reoxygenation injury to show the modulation of the changes in ROS generation, cell viability and apoptosis.
  
  
  RESULTS
  In vivo, luteolin can ameliorate the impaired mitochondrial morphology, regulating the MAPK pathway to protect MIRI. In vitro, luteolin can affect the oxidation system, mitochondrial membrane potential and MAPK pathway to anti-apoptosis.
  
  
  CONCLUSIONS
  These results reveal a ROS-MAPK mediated mechanism and mitochondrial pathway through which luteolin can protect myocardial ischemia/reperfusion injury.
authors.affiliation: Center for Drug Screening & State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Yu
authors.affiliation: Center for Drug Screening & State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Mengwen
authors.initials: M
authors.lastname: Li
authors.affiliation: Lianyungang TCM Branch, Jiangsu Union Technical Institute, Lianyungang 222007, PR China.
authors.forename: Youqing
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Center for Drug Screening & State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center for Drug Screening & State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Qinghai Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, PR China. Electronic address: shangjing21cn@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Shang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D047311:Luteolin
keywords: Apoptosis; Luteolin; MAPK; Mitochondrial; Myocardial ischemia/reperfusion injury; Reactive oxygen species