Curculigoside attenuates myocardial ischemia‑reperfusion injury by inhibiting the opening of the mitochondrial permeability transition pore

Zhao,Yanbing; Guo,Yuxuan; Chen,Yuqiong; Liu,Shuang; Wu,Nan; Jia,Dalin

doi:10.3892/ijmm.2020.4513

Curculigoside attenuates myocardial ischemia‑reperfusion injury by inhibiting the opening of the mitochondrial permeability transition pore

Authors:
- Yanbing Zhao
- Yuxuan Guo
- Yuqiong Chen
- Shuang Liu
- Nan Wu
- Dalin Jia
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Affiliations: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Central Laboratory, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: February 25, 2020 https://doi.org/10.3892/ijmm.2020.4513
Pages: 1514-1524
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to determine whether curculigoside protects against myocardial ischemia‑reperfusion injury (MIRI) and to investigate the underlying mechanisms. An in vitro model of hypoxia/reoxygenation (H/R) was established by culturing H9c2 cells under hypoxic conditions for 12 h, followed by reoxygenation for 1 h. Cell Counting kit‑8 and lactate dehydrogenase (LDH) assays were subsequently used to examine cell viability and the degree of cell injury. In addition, isolated rat hearts were subjected to 30 min of ischemia followed by 1 h of reperfusion to establish a MIRI model. Triphenyltetrazolium chloride (TTC) staining was performed to measure the infarct size. Furthermore, TUNEL staining and flow cytometry were employed to evaluate cell apoptosis. The opening of the mitochondrial permeability transition pore (MPTP) and changes in the mitochondrial membrane potential (ΔΨm) were assessed. Reverse transcription‑quantitative PCR and western blot analysis were performed to investigate the expression levels of mitochondrial apoptosis‑related proteins. Curculigoside pre‑treatment significantly improved cell viability, decreased cell apoptosis and LDH activity, and reduced the infarct size and myocardial apoptosis in vitro and ex vivo, respectively. Moreover, curculigoside markedly inhibited MPTP opening and preserved the ΔΨm. In addition, curculigoside significantly decreased the expression of cytochrome c, apoptotic protease activating factor‑1, cleaved caspase‑9 and cleaved caspase‑3. Notably, atractyloside, a known MPTP opener, abrogated the protective effects of curculigoside. On the whole, the present study demonstrated that curculigoside protected against MIRI, potentially by decreasing the levels of mitochondria‑mediated apoptosis via the inhibition of MPTP opening. Therefore, the results obtained in the present study may provide the theoretical basis for the future clinical application of curculigoside.

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