title: Role of carvacrol in cardioprotection against myocardial ischemia/reperfusion injury in rats through activation of MAPK/ERK and Akt/eNOS signaling pathways.
abstract: Carvacrol (CAR) is a compound isolated from some essential oils, many studies have demonstrated its therapeutic potential on different diseases. This study aims to evaluate the protective effect of CAR against myocardial ischemia/reperfusion (I/R) injury in rats. Male adult rats underwent ligation of the left anterior descending coronary artery (LAD) in I/R models. Rats were treated with CAR after LAD. The levels of I/R- induced infarct size, cardiomyocyte apoptosis and cardiac functional impairment were examined. Levels of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) were detected by western blotting. Cardiomyocytes induced by hypoxic reperfusion (H/R) injury were tested by Hoechst 33258. Our results revealed that CAR administration significantly protected the heart function, attenuated myocardial infarct size, increased SOD and CAT levels, reduced MDA level and especially decreased cardiomyocytes apoptosis. Western blotting showed that CAR treatment up-regulated phosphorylated ERK (p-ERK), while producing no impact onp38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK). The cardioprotection of CAR was reversed by the ERK inhibitor PD-98059, demonstrating the involvement of the MAPK/ERK pathway in the anti-apoptotic mechanisms of CAR. Besides, the results in vitro also showed the protective efficiency of CAR on cardiomyocytes H/R injury. Furthermore, pretreatment with CAR markedly increased the activation of Akt/eNOS pathway in cardiomyocytes subjected to H/R, and the protective effects of CAR were abolished in the presence of the Akt inhibitor LY294002. Therefore, the cardioprotective effects of CAR may be attributed to its antioxidant and antiapoptotic activities through activations of the MAPK/ERK and Akt/eNOS signaling pathways.
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Ba
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: E
authors.initials: E
authors.lastname: Mingyao
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Pilong
authors.initials: P
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Shuzhi
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Hanping
authors.initials: H
authors.lastname: Qi
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China. Electronic address: 437343482@qq.com.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D000081007:Cymenes; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D039821:Monoterpenes / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D000081007:Cymenes; D039821:Monoterpenes; C073316:carvacrol; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases
keywords: Akt/eNOS; Carvacrol; Carvacrol (PubChem CID:10364); DAPI (PubChem CID:2954); Fluorescein dUTP (PubChem CID:86753173); MAPK/ERK; Myocardial ischemia/reperfusion injury; PD-98059 (PubChem CID:4713); Sodium pentobarbital (PubChem CID:23676152)