Open Access

Inhibition of autophagy via activation of PI3K/Akt/mTOR pathway contributes to the protection of hesperidin against myocardial ischemia/reperfusion injury

  • Authors:
    • Xuefei Li
    • Xiaorong Hu
    • Jichun Wang
    • Weipan Xu
    • Chunfeng Yi
    • Ruisong Ma
    • Hong Jiang
  • View Affiliations

  • Published online on: July 30, 2018     https://doi.org/10.3892/ijmm.2018.3794
  • Pages: 1917-1924
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hesperidin has been reported to attenuate myocardial ischemia/reperfusion (I/R) injury; however, its effect on autophagy during myocardial I/R and the underlying mechanism remains unknown. The present study aimed to investigate whether hesperidin inhibited I/R‑induced excessive myocardial autophagy through activating the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. Male adult rats were pretreated with hesperidin for a total of 3 days prior to ischemia in the absence or presence of LY294002, a PI3K inhibitor, and then subjected to ischemia for 30 min followed by reperfusion for 4 h. Myocardial infarct size was measured by Evans blue/triphenyltetrazolium chloride staining. Hematoxylin and eosin staining was used for observing the histological changes in the heart, and the serum levels of creatine kinase‑MB (CK‑MB) and cardiac troponin I (cTnI) were measured by enzyme‑linked immunosorbent assay. Additionally, the protein levels of light chain (LC) 3Ⅱ, Beclin1, phosphorylated (p)‑mTOR, p‑Akt and p‑PI3K were determined by western blot analysis. Hesperidin pretreatment significantly decreased the myocardial infarct size, myocardial damage and serum levels of CK‑MB and cTnI. Furthermore, the expression levels of LC3Ⅱ and Beclin1 were significantly downregulated and the expression levels of p‑mTOR, p‑Akt and p‑PI3K were markedly upregulated by hesperidin. However, the aforementioned effects as a result of hesperidin were significantly reversed by the presence of LY294002. These results demonstrated that hesperidin reduced myocardial I/R injury by suppressing excessive autophagy. Activation of the PI3K/Akt/mTOR pathway contributed to the inhibitory effect of hesperidin on excessive autophagy.
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October-2018
Volume 42 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Li X, Hu X, Wang J, Xu W, Yi C, Ma R and Jiang H: Inhibition of autophagy via activation of PI3K/Akt/mTOR pathway contributes to the protection of hesperidin against myocardial ischemia/reperfusion injury. Int J Mol Med 42: 1917-1924, 2018.
APA
Li, X., Hu, X., Wang, J., Xu, W., Yi, C., Ma, R., & Jiang, H. (2018). Inhibition of autophagy via activation of PI3K/Akt/mTOR pathway contributes to the protection of hesperidin against myocardial ischemia/reperfusion injury. International Journal of Molecular Medicine, 42, 1917-1924. https://doi.org/10.3892/ijmm.2018.3794
MLA
Li, X., Hu, X., Wang, J., Xu, W., Yi, C., Ma, R., Jiang, H."Inhibition of autophagy via activation of PI3K/Akt/mTOR pathway contributes to the protection of hesperidin against myocardial ischemia/reperfusion injury". International Journal of Molecular Medicine 42.4 (2018): 1917-1924.
Chicago
Li, X., Hu, X., Wang, J., Xu, W., Yi, C., Ma, R., Jiang, H."Inhibition of autophagy via activation of PI3K/Akt/mTOR pathway contributes to the protection of hesperidin against myocardial ischemia/reperfusion injury". International Journal of Molecular Medicine 42, no. 4 (2018): 1917-1924. https://doi.org/10.3892/ijmm.2018.3794