Kukoamine A Activates Akt/GSK-3β Pathway to Repress Oxidative Stress and Inflammation to Alleviate Myocardial Ischemia-reperfusion Injury

Jianmao      Hong; Yanqiong      Ye; Dingwen      Zheng; Ximing      Qian

doi:10.2174/0115701808235958230923042422

Abstract

Background: Myocardial ischemia-reperfusion injury (MI/RI) is a serious complication after revascularization of myocardial infarction, which causes myocardium damage. Kukoamine A (KuA) can repress oxidative stress and neuronal apoptosis in cerebral ischemia animal models.

Objective: In the present study, our objective was to explore the role of KuA in MI/RI and the underlying mechanism of KuA in oxidative stress and inflammation of MI/RI.

Methods: H9c2 cells’ cytotoxicity was detected using the lactate dehydrogenase (LDH) assay kit. ROS level was measured by immunofluorescence. Male C57BL/6 mice were used to establish MI/RI mice by ligating the left anterior descending coronary artery (LAD).

Results: KuA treatment decreased the apoptosis and the cytotoxicity, increased the viability, and reduced the activities of myocardial infarction markers (CKMB, MYO, and cTnI) in hypoxia/ reoxygenation (H/R)-induced H9c2 cells. KuA reduced the levels of ROS, MDA, and inflammatory factors (IL-6, IL-1β, and TNF-α), and facilitated MMP and SOD levels in H/R-induced H9c2 cells. Besides, KuA activated Akt/GSK-3β axis, which was repressed by PI3K inhibitor LY294002. Moreover, KuA improved survival times, decreased the infarct size of mice, and recovered cardiac function in MI/RI mice. Finally, KuA alleviated MI/RI through Akt/GSK-3β pathway in vivo.

Conclusion: Thus, KuA exerts a protective function in MI/RI through the Akt/GSK-3β axis to repress oxidative stress and inflammation.

Keywords: Kukoamine A, Akt/GSK-3β pathway, myocardial ischemia-reperfusion injury, myocardial infarction, cardiomyocytes, superoxide dismutase.

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DOI https://dx.doi.org/10.2174/0115701808235958230923042422	Print ISSN 1570-1808
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Kukoamine A Activates Akt/GSK-3β Pathway to Repress Oxidative Stress and Inflammation to Alleviate Myocardial Ischemia-reperfusion Injury

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