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

Li,Xuefei; Hu,Xiaorong; Wang,Jichun; Xu,Weipan; Yi,Chunfeng; Ma,Ruisong; Jiang,Hong

doi:10.3892/ijmm.2018.3794

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
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Affiliations: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Cardiology, Huangshi Center Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, Hubei 435000, P.R. China, Department of Cardiology, Wuhan No. 1 Hospital, Wuhan, Hubei 430060, P.R. China
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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