Oxidative stress suppression by luteolin-induced heme oxygenase-1 expression
Luteolin, a flavonoid that exhibits antioxidative properties, exerts myocardial protection effects.However, the underlying molecular mechanisms are not yet fully understood.To investigate the effects of luteolin on myocardial injury protection and its possible mechanisms, a myocardial injury model was established with intragastric administration of 4mg/kg isoproterenol (ISO) to male Sprague-Dawley rats (200-220)g daffy for 2 days.We found that pretreatment of luteolin (160, 80 and 40mg/kg, i.g., respectively) daily for 15 days can prevent ISO-induced myocardial damage, including decrease of serum cardiac enzymes, improvement electrocardiography and heart vacuolation.Luteolin also improved the free radical scavenging and antioxidant potential, suggesting one possible mechanism of luteolin-induced cardio-protection is mediated by blocking the oxidative stress.To clarify the mechanisms, we performed the in vitro study by hydrogen peroxide (H2O2)-induced cytotoxicty model in H9c2 cells.We found that luteolin pretreatment prevented apoptosis, increased the expression of heme oxygenase-1 (HO-1), and enhanced the binding of Nrf2 to the antioxidant response element, providing an adaptive survival response against H2O2-derived oxidative cytotoxicity.The addition of Znpp, a selective HO-1 competitive inhibitor, reducedthe cytoprotective ability of lutoolin, indicating the vital role of HO-1 on these effects.Luteolin also activated Akt and ERK, whereas the addition of LY294002 and U0126, the pharmacologic inhibitors of PI3K and ERK, attenuated luteolin-induced HO-1 expression and cytoprotective effect.Taken together, the above findings suggest that luteolin protects against myocardial injury and enhances cellular antioxidant defense capacity through the activation of Akt and ERK signal pathways that leads to Nrf2 activation, and subsequently HO-1 induction.
Flavonoid Antioxidants Cardioprotection Apoptosis
SUN Gui-bo WANG Hong-wei SUN Xiao-bo SUN Xiao WANG Min YE Jing-xue SI Jian-yong XU Hui-bo MENG Xiang-bao QIN Meng SUN Jing
Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine,Ministry Center for Translational Medicine,Medical School of Nanjing University,Nanjing 210093,China Jilin Agricultural University,Changchun 130021,China Academy of Chinese Medical Sciences of Jilin Province,Changchun 130021,China
国内会议
北京
英文
97-110
2013-11-01（万方平台首次上网日期，不代表论文的发表时间）