Protective effect of celastrol on myocardial ischemia-reperfusion injury.

Abstract

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-α, IL-1ß, and nuclear factor-K B (NF-K B) 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-α and IL-1ß. Meanwhile, NF-K B 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-K B, and celastrol may be a potential therapeutic agent for preventing MIRI.

• Authors: Xiaoyan Li, Nan Wu, Lu Zou, Dalin Jia
• Journal: Anatolian journal of cardiology (Anatol J Cardiol) Vol. 18 Issue 6 Pg. 384-390 (Dec 2017) ISSN: 2149-2271 [Electronic] Turkey
• PMID: 29256892 (Publication Type: Journal Article)

Chemical References

• Cardiotonic Agents
• Drugs, Chinese Herbal
• Pentacyclic Triterpenes
• Triterpenes
• celastrol

Topics

• Cardiotonic Agents (pharmacology, therapeutic use)
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Humans
• Myocardial Infarction
• Myocardial Reperfusion Injury (prevention & control)
• Myocytes, Cardiac (drug effects)
• Pentacyclic Triterpenes
• Tripterygium
• Triterpenes (pharmacology, therapeutic use)