A Single, Acute Astragaloside IV Therapy Protects Cardiomyocyte Through Attenuating Superoxide Anion-Mediated Accumulation of Autophagosomes in Myocardial Ischemia-Reperfusion Injury.

Kai-Yu Huang,Yang-Pei Peng,Kang-Ting Ji,Yong-Wei Yu,Yang-Jing Xue,Jin-Sheng Wang,Shuai Liu,Ying-Ying Zhou

doi:10.3389/fphar.2021.642925

Abstract

Myocardial ischemia-reperfusion (I/R) injury, characterized by myocardial cell death (e.g., apoptosis) and generation of reactive oxygen species (ROS) such as superoxide (O2 ·−) and hydrogen peroxide (H2O2), is a serious threat to human health and property. Saponin astragaloside IV (ASIV), extracted from Chinese herbal medicine astragalus, is effective in resolving multiple pathological issues including myocardial I/R injury. Recent studies have shown that autophagy is regulated by ROS and plays an important role in myocardial I/R injury. However, regulation of autophagy by ASIV during myocardial I/R injury and the role of specific ROS involved in the process have been rarely reported. In the present study, we found that SOD2 was downregulated and O2 ·− was upregulated in H2O2-induced H9C2 cardiac myocyte injury in vitro and myocardial I/R injury in vivo, while such alterations were reversed by ASIV. ASIV possessed the ability to alleviate myocardial I/R injury via attenuating I/R-caused autophagosome accumulation. Upregulate of O2 ·− by 2-methoxyestradiol (2-ME) reversed the effect of ASIV-mediated autophagy regulation, which suggested that O2 ·− was vital in this process. In conclusion, our results contribute to understanding the mechanism of ASIV-induced cardioprotective effect.

Highlights

Myocardial infarction (MI) is one of the leading causes of death in the world threatening human life
Our findings indicate that the infarct size in mice treated with astragaloside IV (ASIV) was decreased, in comparison with that in the I/R group (Figures 1C,D)
Relative to the sham group, the serum level of CK-MB was markedly elevated in the I/R group; this tendency was counteracted by ASIV (Figure 1E)

Summary

Introduction

Myocardial infarction (MI) is one of the leading causes of death in the world threatening human life. Searching for strategies to alleviate myocardial I/R injury is of urgency for the treatment of MI. Increasing studies have confirmed that autophagy is a ubiquitous pathophysiological process in myocardial I/R injury (Gustafsson and Gottlieb, 2008; Sadoshima, 2008). Studies have found that autophagy induced by ischemia is beneficial while autophagy during reperfusion is destructive (Matsui et al, 2007), the role of autophagy in myocardial I/R injury is still not conclusive. Enhancing autophagy has been reported to both promote and inhibit cell death in myocardial I/R injury (Ma et al, 2012; Zhao et al, 2013). It is clear that manipulation of autophagy might be an effective way to reverse cell death during myocardial I/R injury

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Conclusion