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Nobiletin attenuates cardiac dysfunction, oxidative stress, and inflammatory in streptozotocin: induced diabetic cardiomyopathy

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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 p67phox, p22phox, and p91phox, 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.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No. 81470516) and the Natural Science Foundation of Hubei Province, China (No. 2014CFB738).

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    Authors and Affiliations

    1. Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People’s Republic of China

      Ning Zhang, Zheng Yang, Shi-Zhao Xiang, Ya-Ge Jin, Wen-Ying Wei, Zhou-Yan Bian, Wei Deng & Qi-Zhu Tang

    2. Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, People’s Republic of China

      Ning Zhang, Zheng Yang, Shi-Zhao Xiang, Ya-Ge Jin, Wen-Ying Wei, Zhou-Yan Bian, Wei Deng & Qi-Zhu Tang

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    1. Ning Zhang
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    Correspondence to Qi-Zhu Tang.

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    Ning Zhang and Zheng Yang are joint first authors.

    Ning Zhang and Zheng Yang have contributed equally to this manuscript.

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    Zhang, N., Yang, Z., Xiang, SZ. et al. Nobiletin attenuates cardiac dysfunction, oxidative stress, and inflammatory in streptozotocin: induced diabetic cardiomyopathy. Mol Cell Biochem 417, 87–96 (2016). https://doi.org/10.1007/s11010-016-2716-z

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