title: Nobiletin attenuates cardiac dysfunction, oxidative stress, and inflammatory in streptozotocin: induced diabetic cardiomyopathy.
abstract: Diabetic cardiomyopathy, characterized by the presence of diastolic and/or systolic myocardial dysfunction, is one of the major causes of heart failure. Nobiletin, which is extracted from the fruit peel of citrus, is reported to possess anti-inflammatory, anti-oxidative, and hypolipidemic properties. The purpose of this study was to investigate whether nobiletin exerts the therapeutic effect on streptozotocin-induced diabetic cardiomyopathy (DCM) in mice. 80 experimental male C57BL mice were randomly assigned into four groups: sham + vehicle (VEH/SH), sham + nobiletin (NOB/SH), DCM + vehicle (VEH/DM), and DCM + nobiletin (NOB/DM). Nobiletin treatment ameliorated cardiac dysfunction in the DCM group, as shown by the result of echocardiography and hemodynamic measurements. Nobiletin treatment also blunted the mRNA expression of NADPH oxidase isoforms p67(phox), p22(phox), and p91(phox), and abated oxidative stress. Although administration of diabetic mice with nobiletin did not significantly effect the level of blood glucose, it decreased the TGF-β1, CTGF, fibronectin, and collagen Iα expressions and blunted cardiac fibrosis. In addition, nobiletin inhibited the activation of c-Jun NH2-terminal kinase (JNK), P38, and NF-κB in the cardiac tissue of diabetic mice. Collectively, our study indicates that treatment with nobiletin mitigates cardiac dysfunction and interstitial fibrosis, and these beneficial of nobiletin may belong to the suppression of JNK, P38, and NF-κB signaling pathways.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, People's Republic of China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, People's Republic of China.
authors.forename: Shi-Zhao
authors.initials: SZ
authors.lastname: Xiang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, People's Republic of China.
authors.forename: Ya-Ge
authors.initials: YG
authors.lastname: Jin
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, People's Republic of China.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Wei
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, People's Republic of China.
authors.forename: Zhou-Yan
authors.initials: ZY
authors.lastname: Bian
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China. qztang@whu.edu.cn.|Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, People's Republic of China. qztang@whu.edu.cn.
authors.forename: Qi-Zhu
authors.initials: QZ
authors.lastname: Tang
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D058065:Diabetic Cardiomyopathies / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D047309:Flavones / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D047309:Flavones; C008661:nobiletin
keywords: Diabetic cardiomyopathy; Inflammation; Nobiletin; Oxidative stress; Streptozotocin