title: Inhibition of 12/15 lipoxygenase by baicalein reduces myocardial ischemia/reperfusion injury via modulation of multiple signaling pathways.
abstract: 12/15-Lipoxygenase (LOX) is a member of the LOX family that catalyzes the step from arachidonic acid to hydroxy-eicosatetraenoic acids (HETEs). Previous studies demonstrated that 12/15-LOX plays a critical role in the development of atherosclerosis, hypertension, heart failure, and other diseases; however, its role in myocardial ischemic injury was contraversal. Here, we investigated the inhibition of 12/15-LOX by baicalein on acute cardiac injury and dissected its molecular mechanism. In a mouse model of acute ischemia/reperfusion (I/R) injury, 12/15-LOX was significantly upregulated in the peri-infarct area surrounding the primary infarction. In cultured cardiac myocytes, baicalein suppressed apoptosis and caspase 3 activity in response to simulated ischemia/reperfusion (I/R). Moreover, administration of 12/15-LOX inhibitor, baicalein, significantly attenuated myocardial infarct size induced by I/R injury. Moreover, baicalein treatment significantly inhibited cardiomyocyte apoptosis, inflammatory responses and oxidative stress in the heart after I/R injury. The mechanisms underlying these effects were associated with the activation of ERK1/2 and AKT pathways and inhibition of activation of p38 MAPK, JNK1/2, and NF-kB/p65 pathways in the I/R-treated hearts and neonatal cardiomyoctes. Our data indicated that 12/15-LOX inhibitor baicalein can prevent myocardial I/R injury by modulation of multiple mechanisms, and suggest that baicalein could represent a novel therapeutic drug for acute myocardial infarction.
authors.affiliation: Department of Pathology, Physiology and Pathophysiology, Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Capital Medical University, Ministry of Education, No. 10 Xitoutiao You An Men, Beijing, 100069, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Song
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wang
authors.forename: Cui
authors.initials: C
authors.lastname: Tian
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Zeng
authors.forename: Erhe
authors.initials: E
authors.lastname: Gao
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Kang
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Li
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D002478:Cells, Cultured; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction
chemical_list: C475064:12-15-lipoxygenase; D044950:Flavanones; D016859:Lipoxygenase Inhibitors; C006680:baicalein; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase