Ye Lin - School of Medical and Health Engineering, Changzhou University, Changzhou ۲۱۳۱۶۴, P.R. China
Xin Yang - Food Science and Technology Program, Department of Chemistry, Faculty of Science, National University of Singapore, Singapore ۱۱۷۵۹۷, Singapore
Yan Li - School of Medical and Health Engineering, Changzhou University, Changzhou ۲۱۳۱۶۴, P.R. China
De-jian Huang - Food Science and Technology Program, Department of Chemistry, Faculty of Science, National University of Singapore, Singapore ۱۱۷۵۹۷, Singapore
Zhi-qin Sun - Changzhou Second People’s Hospital, Changzhou ۲۱۳۰۰۰, P.R. China

Objective(s): Luteolin is a flavone that provides defense against myocardial ischemia/reperfusion (I/R) injury. However, this compound is subjected to methylation mediated by catechol-O-methyltransferase (COMT), thus influencing its pharmacological effect. To synthesize a new flavone from luteolin that avoids COMT-catalyzed methylation and find out the protective mechanism of LUA in myocardial I/R injury.Materials and Methods: Luteolin and ۲,۲’-azobis (۲-amidinopropane) dihydrochloride (AAPH) were used to synthesize the new flavone known as LUAAPH-۱ (LUA). Then, the myocardial ischemia/reperfusion injury cell model was established using H۹c۲ cells to detect the effect in myocardial ischemia/reperfusion regulation and to identify the underlying mechanism. Results: Pretreatment with LUA (۲۰ μmol/l) substantially increased cell viability while reducing cell apoptosis rate and caspase-۳ expression induced by I/R, and the protective effect of LUA on cell viability was stronger than diosmetin, which is the major methylated metabolite of luteolin. In addition, intracellular reactive oxygen species (ROS) production and calcium accumulation were both inhibited by LUA. Furthermore, we identified that LUA markedly relieved the promotive effects of I/R stimulation upon JNK and p۳۸ phosphorylation.Conclusion: LUT pretreatment conveys significant cardioprotective effects after myocardial I/R injury, and JNK and p۳۸ MAPK signaling pathway may be involved.

۲,۲’-azobis - (۲-amidinopropane) - dihydrochloride (AAPH), Catechol-O-methyltransferase (COMT) H۹C۲, Luteolin, Myocardial ischemia - reperfusion