Nobiletin protects against myocardial injury and myocardial apoptosis following coronary microembolization via activating PI3K/Akt pathway in rats
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.
KeywordsNobiletin Coronary microembolization Apoptosis PI3K/Akt Oxidative stress
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.
This study was supported by the Guangxi Natural Science Foundation (No. 2017GXNSFAA198214).
Compliance with ethical standards
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.
Conflict of interest
The authors declare that they have no conflict of interest.
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