Aloin antagonizes stimulated ischemia/reperfusion-induced damage and inflammatory response in cardiomyocytes by activating the Nrf2/HO-1 defense pathway

Abstract

Myocardial ischemia/reperfusion injury (I/RI) frequently incurs in acute myocardial infarction with high morbidity and mortality worldwide and is characterized with cardiomyocyte apoptosis and inflammatory response. Aloin is a major anthraquinone from Aloe species and fulfills pleiotropic protective functions in several disease models including hepatic injury. Nevertheless, the potential of aloin in MI/RI remains elusive. Intriguingly, aloin had modest cytotoxicity in H9c2 cardiomyocytes. Importantly, aloin dose-dependently ameliorated cell viability that was inhibited in response to simulated ischemia/reperfusion (SI/R) stimulation. Moreover, the enhanced apoptosis in cells under SI/R conditions were reduced after aloin treatment, concomitant with the decrease in pro-apoptotic Bax protein levels and increase in anti-apoptotic Bcl-2 protein expression. Of interest, aloin administration attenuated SI/R-induced oxidant stress by decreasing reactive oxygen species (ROS) production, lactate dehydrogenase (LDH), and malondialdehyde (MDA) release and increasing activity of anti-oxidant stress enzyme superoxide dismutase (SOD). Additionally, the elevated pro-inflammatory cytokine levels were counteracted after aloin treatment in cells under SI/R conditions, including TNF-α, IL-6, and IL-1β. Mechanically, aloin further enforced the activation of the NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Noticeably, blockage of this pathway by si-Nrf2 transfection blunted aloin-mediated cardioprotective efficacy against SI/R-evoked oxidative stress injury and inflammatory response. Thus, these findings corroborate that aloin may antagonize SI/R-induced cardiomyocyte injury by attenuating excessive oxidative stress and inflammation, thereby endorsing its potential as a promising therapeutic agent against myocardial infarction.

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All data generated or analyzed during this study are included in this published article.

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Funding

This study was supported by grant from National Science Foundation of China (81670378 to Yuehui Wang, 81800228 to Zhihao Wang) Jilin Province Science and Technology Department Project (20180101166JC, 20190701007GH to Yuehui Wang).

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Correspondence to Yuehui Wang.

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Sun, W., Wang, Z., Sun, M. et al. Aloin antagonizes stimulated ischemia/reperfusion-induced damage and inflammatory response in cardiomyocytes by activating the Nrf2/HO-1 defense pathway. Cell Tissue Res (2021). https://doi.org/10.1007/s00441-020-03345-z

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Keywords

  • Aloin
  • Ischemia/reperfusion
  • Cardiomyocytes
  • Injury
  • Inflammatory response
  • Nrf2-HO-1 axis
  • Radiation-induced pulmonary fibrosis