title: Peroxisome proliferator-activated receptor γ (PPARγ) mediates the protective effect of quercetin against myocardial ischemia-reperfusion injury via suppressing the NF-κB pathway.
abstract: Quercetin plays an important role in myocardial ischemia and reperfusion injury (IRI). However, the underlying mechanism for the protective effect of quercetin is largely unclear. In this study, we explored the protected effects of quercetin against myocardial IRI and its molecular mechanisms. Quercetin, GW9962 (PPARγ antagonist) or PPARγ-siRNA was administered alone or in combination prior to myocardial IRI in mice or to hypoxia and reoxygenation (H/R) treatment in H9C2 cells. Infarct size was evaluated by TTC staining after reperfusion. Myocardial injury was assessed by the serum levels of AST, CK-MB, cardiac troponin T (cTnT) and LDH. Cardiac function was measured by echocardiography. Oxidative stress injury was evaluated by analyses of inducible nitric oxide synthase (iNOS), MDA, SOD and glutathione peroxidase (GSH-PX) levels and by reactive oxygen species (ROS) detection. Myocardium apoptosis was evaluated by TUNEL staining, cleaved caspase-3 and Annexin V/PI detection. Moreover, activation of the NF-κB pathway was reflected by phosphorylation of IκB (p-IκB) and nuclear translocation of NF-κB p65. We reported that pretreatment of quercetin significantly improved cardiac function, diminished myocardial injury and reduced the infarct size. Myocardium oxidative damage and apoptosis were remarkably improved by quercetin treatment in vivo andin vitro. Quercetin also suppressed the activation of the NF-κB pathway induced by myocardial IRI. GW9662 or PPARγ knockdown partially attenuated these cardioprotective effects of quercetin during myocardial IRI. In conclusion, our findings suggest that quercetin ameliorated IRI-induced heart damage via PPARγ activation and the underlying mechanism might involve the inhibition of NF-κB pathway by PPARγ activation.
authors.affiliation: Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University No. 160 Pujian Road, Shanghai 200127, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University No. 160 Pujian Road, Shanghai 200127, China.
authors.forename: Zhangjie
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, School of Medicine, Shanghai Jiao Tong University No. 280 Chongqing South Road, Shanghai 200025, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University No. 160 Pujian Road, Shanghai 200127, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, School of Medicine, Shanghai Jiao Tong University No. 280 Chongqing South Road, Shanghai 200025, China.
authors.forename: Xiuzhi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University No. 160 Pujian Road, Shanghai 200127, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University No. 160 Pujian Road, Shanghai 200127, China.
authors.forename: Song
authors.initials: S
authors.lastname: Xue
keywords: NF-κB pathway; Quercetin; ischemia-reperfusion injury; myocardium; peroxisome proliferator-activated receptor γ