Costunolide Protects Myocardial from Ischemia Reperfusion Injury through Nrf2 Activation

Abstract Purpose Costunolide (Cos) is a naturally occurring sesquiterpene lactone that exhibits anti-oxidative properties. In this study, we demonstrated the protective mechanism of Cos against ischemia/reperfusion (I/R)-induced heart injury. Methods C57BL/6 mice were pretreated with Cos (10 mg/kg/day) or 1% CMC-Na for 1 week. The left anterior descending coronary artery (LAD) was ligated for 30 minutes for ischemia, and followed by ligation release for 4 hours for reperfusion. H9c2 cells challenged with tert-butyl hydroperoxide (TBHP) were used for in vitro studies. Results Pretreatment of Cos significantly reduced myocardial infarct size, serum CK-MB and LDH level in I/R injured heart. Cos administration significantly attenuated the amount of reactive oxygen species (ROS) and ameliorated the apoptosis both in in vitro and in vivo studies. Further investigation revealed that Cos significantly increased the expression of heme oxygenase 1 (HO-1) and NAD(P)H [quinone] dehydrogenase 1 (NQO-1). Meanwhile Cos increased B-cell lymphoma-2(Bcl-2) and decreased the BCL2-Associated X Protein (Bax) protein level. Silence of nuclear factor erythroid 2-related factor (Nrf2) significantly reverses the protective effect of Cos in TBHP-challenged H9C2 cells. Conclusion Our data clearly showed that Cos reduced TBHP challenged H9c2 cells and attenuated myocardial I/R injury through Nrf2 activation. These results indicate that Cos might be benefit in the therapy of myocardial I/R injury.