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Piperine protects against myocardial ischemia/reperfusion injury by activating the PI3K/AKT signaling pathway

  • Authors:
    • Yun-Peng Li
    • Zhen Chen
    • Yu-Hua Cai
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovasology, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China, Department of Emergency and Evidence‑Based Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China, Department of Cardiovasology, Jingzhou First Municipal Hospital, Jingzhou, Hubei 434000, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 374
    |
    Published online on: February 19, 2021
       https://doi.org/10.3892/etm.2021.9805
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Abstract

Piperine (PIP) exerts numerous pharmacological effects and its involvement in endoplasmic reticulum (ER) stress (ERS)‑led apoptosis has garnered attention. The present study focused on whether PIP played protective effects on hypoxia/reoxygenation (H/R)‑induced cardiomyocytes by repressing ERS‑led apoptosis. The potential molecular mechanisms in association with the PI3K/AKT signaling pathway were investigated. Primary neonatal rat cardiomyocytes (NRCMs) were isolated and randomized into four groups: control + vehicle group, control + PIP group, H/R + vehicle group and H/R + PIP group. The H/R injury model was constructed by 4 h of hypoxia induction followed by 6 h of reoxygenation. A total of 10 µM PI3K/AKT inhibitor LY294002 was supplemented to the cells during the experiments. Cell viability and myocardial enzymes were detected to evaluate myocardial damage. A flow cytometry assay was performed to assess apoptotic response. Western blot analysis was performed to detect the expression of related proteins including PI3K, AKT, CHOP, GRP78 and cleaved caspase‑12. The results showed that H/R markedly promoted myocardial damage as shown by the increased release of lactate dehydrogenase and creatine kinase levels, but a reduction in cell viability. In addition, ERS‑induced apoptosis was markedly promoted by H/R in NRCMs, as shown by the increased apoptotic rates and expression of C/EBP‑homologous protein, endoplasmic reticulum chaperone BiP and caspase‑12. PIP administration reversed cell injury and ERS‑induced apoptosis in H/R. Mechanistic studies concluded that the apoptosis‑inhibitory contributions and cardio‑favorable effects of PIP were caused partly by the activation of the PI3K/AKT signaling pathway, which was verified by LY294002 administration. To conclude, PIP can reduce ERS‑induced apoptosis by activating the PI3K/AKT signaling pathway during the process of H/R injury, which could be a potential therapeutic target for the treatment of myocardial ischemia/reperfusion injury.
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Copy and paste a formatted citation
Spandidos Publications style
Li Y, Chen Z and Cai Y: Piperine protects against myocardial ischemia/reperfusion injury by activating the PI3K/AKT signaling pathway. Exp Ther Med 21: 374, 2021.
APA
Li, Y., Chen, Z., & Cai, Y. (2021). Piperine protects against myocardial ischemia/reperfusion injury by activating the PI3K/AKT signaling pathway. Experimental and Therapeutic Medicine, 21, 374. https://doi.org/10.3892/etm.2021.9805
MLA
Li, Y., Chen, Z., Cai, Y."Piperine protects against myocardial ischemia/reperfusion injury by activating the PI3K/AKT signaling pathway". Experimental and Therapeutic Medicine 21.4 (2021): 374.
Chicago
Li, Y., Chen, Z., Cai, Y."Piperine protects against myocardial ischemia/reperfusion injury by activating the PI3K/AKT signaling pathway". Experimental and Therapeutic Medicine 21, no. 4 (2021): 374. https://doi.org/10.3892/etm.2021.9805
Copy and paste a formatted citation
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Spandidos Publications style
Li Y, Chen Z and Cai Y: Piperine protects against myocardial ischemia/reperfusion injury by activating the PI3K/AKT signaling pathway. Exp Ther Med 21: 374, 2021.
APA
Li, Y., Chen, Z., & Cai, Y. (2021). Piperine protects against myocardial ischemia/reperfusion injury by activating the PI3K/AKT signaling pathway. Experimental and Therapeutic Medicine, 21, 374. https://doi.org/10.3892/etm.2021.9805
MLA
Li, Y., Chen, Z., Cai, Y."Piperine protects against myocardial ischemia/reperfusion injury by activating the PI3K/AKT signaling pathway". Experimental and Therapeutic Medicine 21.4 (2021): 374.
Chicago
Li, Y., Chen, Z., Cai, Y."Piperine protects against myocardial ischemia/reperfusion injury by activating the PI3K/AKT signaling pathway". Experimental and Therapeutic Medicine 21, no. 4 (2021): 374. https://doi.org/10.3892/etm.2021.9805
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