ISSN 2149-2263 | E-ISSN 2149-2271
Protective effect of celastrol on myocardial ischemia–reperfusion injury [Anatol J Cardiol]
Anatol J Cardiol. 2017; 18(6): 384-390 | DOI: 10.14744/AnatolJCardiol.2017.7866

Protective effect of celastrol on myocardial ischemia–reperfusion injury

Xiaoyan Li, Nan Wu, Lu Zou, Dalin Jia
The First Affiliated Hospital of China Medical University, Liaoning-China

Objective: Celastrol, a major active constituent of Tripterygium wilfordii, has antioxidant, anti-inflammatory, and anticancer effects. However, whether celastrol can exert protective effect on myocardial ischemia–reperfusion injury (MIRI) is unknown. The aim of this study was to test the protective effect of celastrol on MIRI and elucidate its underlying mechanism.
Methods: Cardiomyocytes (H9c2 cells) were subjected to hypoxia for 8 h followed by reoxygenation for 4 h to create hypoxia/reoxygenation (H/R) model, an in vitro MIRI model. Celastrol was added to the medium 60 min before the H/R process. Cell viability was detected using MTT assay. Myocardial injury was evaluated by measuring lactate dehydrogenase (LDH) and creatine kinase MB isoenzyme (CK-MB) activity. Changes in mRNA and protein expression of TNF-⍺, IL-1β, and nuclear factor-KB (NF-KB) were measured with RT-qPCR assay and western blot analysis.
Results: Results showed that low-dose celastrol (20 and 50 nM) treatment significantly increased cell viability and decreased LDH and CK-MB activity in the condition of H/R, but high-dose celastrol (200 and 400 nM) resulted in extra injury to cardiomyocytes. Moreover, treatment with 50 nM celastrol significantly downregulated mRNA and protein expression of TNF-⍺ and IL-1β. Meanwhile, NF-KB mRNA and protein in the nucleus were also correspondingly reduced.
Conclusion: Our study demonstrated that low-dose celastrol could prevent MIRI in cardiomyocytes by inhibiting the activation of NF-KB, and celastrol may be a potential therapeutic agent for preventing MIRI.

Keywords: celastrol, myocardial ischemia–reperfusion injury, nuclear factor-KB, TNF-⍺, IL-1β

Xiaoyan Li, Nan Wu, Lu Zou, Dalin Jia. Protective effect of celastrol on myocardial ischemia–reperfusion injury. Anatol J Cardiol. 2017; 18(6): 384-390

Corresponding Author: Dalin Jia, China
Manuscript Language: English

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