Artesunate alleviates myocardial ischemia/reperfusion-induced myocardial necrosis in rats and hypoxia/reoxygenation-induced apoptosis in H9C2 cells via regulating the FAK/PI3K/Akt pathway.

Content Provider	Europe PMC
Author	Fan, Shunyang Zhang, Deyin Liu, Fuyun Yang, Yuqi Xu, Hongliang
Copyright Year	2020
Abstract	BackgroundThe various anti-inflammatory, anti-apoptotic, and antioxidant effects of Artesunate (Art) have been explored in numerous studies. This study aimed to evaluate the function of Art on myocardial necrosis in apoptotic cardiomyocytes in vivo and in vitro.MethodsSprague Dawley (SD) rats were randomly divided into groups: a control group, a myocardial ischemia reperfusion (MI/R) group, and MI/R+ Art groups. To establish a MI/R model, rats were subjected to left anterior descending artery ischemia for 45 minutes, and then reperfusion for 2 hours. Hypoxia was induced in H9C2 cells by subjecting them to hypoxic conditions at 37 °C for 4 hours, before placing them in a normoxic chamber for 2 hours. The test methods were used in this test, such as echocardiography, enzyme-linked immunosorbent assay (ELISA), HE staining, TUNEL staining, immunohistochemistry, flow cytometry, western blot, and CCK-8 assay.ResultsArt improved myocardial systolic function caused by MI/R injury in vivo. Simultaneously, Art reduced the levels of cardiac troponin I (cTnl), creatine kinase-MB (CK-MB) and myohemoglobin (Mb) in vivo and in vitro. Moreover, Art inhibited cardiomyocyte apoptosis in vivo and in vitro. The focal adhesion kinase (FAK)/phosphatidylinositide-3 kinases (PI3K)/AKT signaling pathway was also activated by Art in vivo and in vitro. Furthermore, after inhibitor PF573228 was added, Art inhibited apoptosis in H9C2 cells via activation of the FAK/PI3K/AKT signaling pathway in vitro.ConclusionsThis study confirms that Art alleviated MI/R injury and inhibited cardiomyocyte apoptosis in vivo and in vitro. Art exerted an inhibitory effect on cardiomyocyte apoptosis by activating the FAK/PI3K/AKT signaling pathway. Therefore, Art may serve as an alternative treatment for MI/R injury.
ISSN	23055839
Volume Number	8
PubMed Central reference number	PMC7661874
Issue Number	20
PubMed reference number	33209871
Journal	Annals of Translational Medicine [Ann Transl Med]
e-ISSN	23055847
DOI	10.21037/atm-20-5182
Language	English
Publisher	AME Publishing Company
Publisher Date	2020-10-01
Access Restriction	Open
Rights License	Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0. 2020 Annals of Translational Medicine. All rights reserved.
Subject Keyword	Artesunate myocardial ischemia/reperfusion hypoxia/reoxygenation apoptosis focal adhesion kinase/phosphatidylinositide-3 kinases/Akt pathway (FAK/PI3K/Akt pathway)
Content Type	Text
Resource Type	Article
Subject	Medicine