Open Access

Schizandrin B attenuates hypoxia/reoxygenation injury in H9c2 cells by activating the AMPK/Nrf2 signaling pathway

  • Authors:
    • Bo Zhao
    • Guang-Ping Li
    • Jian-Jun Peng
    • Li-Hui Ren
    • Li-Cheng Lei
    • Hui-Ming Ye
    • Zuo-Yan Wang
    • Sheng Zhao
  • View Affiliations

  • Published online on: January 18, 2021     https://doi.org/10.3892/etm.2021.9651
  • Article Number: 220
  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Schizandrin B exhibits prominent antioxidant and anti-inflammatory effects, and plays an important role in ameliorating myocardial ischemia/reperfusion injury. However, the underlying protective mechanisms remain to be elucidated. The aim of the present study was to explore the cardioprotective effects of schizandrin B against hypoxia/reoxygenation (H/R)-induced H9c2 cell injury, focusing on the role of the adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in this process. The results showed that schizandrin B attenuated the H/R-induced decrease in cell viability and the increase in lactate dehydrogenase release, as well as the apoptosis rate in H9c2 cells. Schizandrin B also mitigated H/R-induced oxidative stress, as illustrated by the decrease in intracellular reactive oxygen species generation, malondialdehyde content and NADPH oxidase 2 expression, and the increase in antioxidant enzyme superoxide dismutase and glutathione peroxidase activities. In addition, schizandrin B reversed the H/R-induced upregulation of pro-inflammatory cytokines [interleukin (IL)-1β (IL-1β) tumor necrosis factor-α, IL-6 and IL-8] and the downregulation of anti-inflammatory cytokines (transforming growth factor-β and IL-10) in the culture supernatant. Notably, schizandrin B increased the expression of Nrf2, NAD(P)H: Quinone oxidoreductase (NQO-1) and heme oxygenase-1 (HO-1) in H/R-treated H9c2 cells, activating the Nrf2 signaling pathway. The cardioprotection of schizandrin B against H/R injury was inhibited by Nrf2 knockdown induced byNrf-2-specific small interfering RNA (siRNA; si-Nrf2) transfection. Furthermore, schizandrin B enhanced phosphorylated (p)-AMPK expression, while AMPK knockdown induced by AMPK-specific siRNA(si-AMPK) transfection remarkably eliminated schizandrin B-induced cardioprotection and reduced Nrf2 expression in H/R-treated H9c2 cells. Taken together, these results suggested that schizandrin B exerts cardioprotection on H/R injury in H9c2 cells due to its antioxidant and anti-inflammatory activities via activation of the AMPK/Nrf2 pathway.
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March-2021
Volume 21 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhao B, Li G, Peng J, Ren L, Lei L, Ye H, Wang Z and Zhao S: Schizandrin B attenuates hypoxia/reoxygenation injury in H9c2 cells by activating the AMPK/Nrf2 signaling pathway. Exp Ther Med 21: 220, 2021
APA
Zhao, B., Li, G., Peng, J., Ren, L., Lei, L., Ye, H. ... Zhao, S. (2021). Schizandrin B attenuates hypoxia/reoxygenation injury in H9c2 cells by activating the AMPK/Nrf2 signaling pathway. Experimental and Therapeutic Medicine, 21, 220. https://doi.org/10.3892/etm.2021.9651
MLA
Zhao, B., Li, G., Peng, J., Ren, L., Lei, L., Ye, H., Wang, Z., Zhao, S."Schizandrin B attenuates hypoxia/reoxygenation injury in H9c2 cells by activating the AMPK/Nrf2 signaling pathway". Experimental and Therapeutic Medicine 21.3 (2021): 220.
Chicago
Zhao, B., Li, G., Peng, J., Ren, L., Lei, L., Ye, H., Wang, Z., Zhao, S."Schizandrin B attenuates hypoxia/reoxygenation injury in H9c2 cells by activating the AMPK/Nrf2 signaling pathway". Experimental and Therapeutic Medicine 21, no. 3 (2021): 220. https://doi.org/10.3892/etm.2021.9651