Luteolin ameliorates rat myocardial ischemia-reperfusion injury through peroxiredoxin II activation

BACKGROUND AND PURPOSE Antioxidants provide a promising therapeutic effect for the cardiovascular disease. Luteolin (LUT), a polyphenolic bioflavonoid, is known to confer cardioprotection, although the underlying mechanism, especially the role of LUT on the antioxidant enzymes (e.g. peroxiredoxin family, PRXs), remains elusive. EXPERIMENTAL APPROACH The current study was designed to evaluate the impact of LUT on MI/R injury in vivo and in vitro, as well as the underlying mechanism with a focus on PRXs signaling. H9c2 cells was used to assess the alterations of PRXs and the other antioxidant enzymes. Oxidative stress, cardiac function, LDH release, ROS and infarct size were also evaluated. KEY RESULTS LUT exerted significant cardioprotective effects in vivo and in vitro via improving cardiac function, increasing the expression of anti-apoptotic protein Bcl-2 and decreasing the pro-apoptotic protein Bax, active-Caspases 3 and 9, associated with MI/R. Mechanistically, LUT markedly enhanced PRX II expression without significant effects on other PRXs, catalase and SOD1. Molecular docking proved that LUT could indeed bind to the enzymatic active pocket of PRX II. Furthermore, down-regulation of PRX II by Ad. Prx II-antisense infection in cellular level and inhibiting activity of PRX II in vivo significantly reversed the cardioprotective effects of LUT. CONCLUSION AND IMPLICATIONS Our findings, for the first time, demonstrated that LUT protects MI/R injury through promoting endogenous antioxidant PRX II signaling, indicating the important beneficial role of PRX II in heart.