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Nobiletin protects against myocardial injury and myocardial apoptosis following coronary microembolization via activating PI3K/Akt pathway in rats

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Abstract

It has been found that use of drugs which upregulate the PI3K/Akt pathway can effectively reduce cardiomyocyte apoptosis which has been induced by coronary microembolization (CME). However, whether this functional protein is able to be modified through pretreatment via nobiletin (NOB) in models of CME has not yet been investigated. Therefore, this study set out to explore the cardioprotective effect of NOB on rats with myocardial injuries induced by CME and also explored the potential mechanism which underlies this cardioprotective effect. The study used 40 Sprague-Dawley (SD) rats, which were randomized into four groups: the sham, CME, CME+NOB, and CME+NOB+LY294002 (LY) groups. Twelve hours after surgery, levels of microinfarct, serum c-troponin I (cTnI), cardiac function, apoptotic index, and oxidative stress [superoxide dismutase (SOD) and malondialdehyde (MDA)] were measured for rats in each group. Western blot analysis was performed to detect any protein involved in the PI3K/Akt pathway. Nobiletin improved cardiac dysfunction which had been induced by CME, decreased serum level of cTnI and MDA, and increased serum SOD activities. In addition, nobiletin inhibited myocardial apoptosis, which may be connected to downregulated apoptotic index, upregulated Bcl-2, and cleaved caspase-3 and Bax, while it increased protein levels in phosphorylated Akt. However, when nobiletin was co-administered with LY294002, a PI3K (phosphatidylinositol 3-kinase)/Akt inhibitor, all of the previously mentioned effects were blocked. Nobiletin is able to inhibit cardiomyocyte apoptosis and can consequently attenuate CME-induced myocardial injuries. These functions are realized through the activation of the PI3K/Akt signaling pathway as well as by reducing oxidative stress.

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Funding

This study was supported by the Guangxi Natural Science Foundation (No. 2017GXNSFAA198214).

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Authors and Affiliations

  1. Department of Cardiology, Nanjing Lishui People’s Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, 211200, China

    Qing Mao

  2. Department of Cardiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, Guangxi Zhuang Autonomous Region, China

    Qing Mao & Yongxiang Lu

  3. Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, Guangxi Zhuang Autonomous Region, China

    Xiulin Liang

  4. Department of Cardiology, The Guangxi Zhuang Autonomous Region Brain Hospital, Liuzhou, 545005, Guangxi Zhuang Autonomous Region, China

    Yufu Wu

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  1. Qing Mao
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  2. Xiulin Liang
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  4. Yongxiang Lu
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Contributions

QM conducted the experiments. XL, YW, and YL participated in research design and data analysis. QM wrote the paper. All the authors read and approved the manuscript.

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Correspondence to Qing Mao.

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The Institutional Animal Care and Use Committees of Guangxi Medical University approved all experiments, and all procedures and processes in this study were conducted as set out by the National Institutes of Health Guidelines on the use of laboratory animals.

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The authors declare that they have no conflict of interest.

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Mao, Q., Liang, X., Wu, Y. et al. Nobiletin protects against myocardial injury and myocardial apoptosis following coronary microembolization via activating PI3K/Akt pathway in rats. Naunyn-Schmiedeberg's Arch Pharmacol 392, 1121–1130 (2019). https://doi.org/10.1007/s00210-019-01661-y

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