Narciclasine attenuates sepsis-induced myocardial injury by modulating autophagy.

Abstract

Acute myocardial injury (AMI) is often secondary to sepsis, which is a life-threatening disease associated with severe cardiac inflammation. Narciclasine, a plant alkaloid isolated from different members of the Amaryllidaceae family, has been extensively characterized as an antitumor and anti-inflammatory compound. In addition, autophagy is critical for sepsis-induced myocardial injury. However, the role and mechanism of autophagy by which narciclasine confers cardioprotection are still unclear. The present study aimed to investigate the underlying mechanism by which narciclasine affects the pathogenesis of sepsis-induced myocardial injury. Narciclasine effectively attenuated LPS-induced myocardial inflammation in vitro and in vivo. In addition, narciclasine protected cardiac function and suppressed the expression of inflammatory cytokines in LPS-induced heart tissue. Furthermore, narciclasine upregulated LPS-induced autophagic activity, and the autophagy inhibitor 3-MA abrogated narciclasine-mediated protection against LPS-induced AMI. Importantly, narciclasine exerted an inhibitory effect on the JNK signaling pathway, and JNK activity was tightly associated with narciclasine-induced autophagy and the consequent protective effects during AMI. Taken together, our findings indicate that narciclasine protects against LPS-induced AMI by inducing JNK-dependent autophagic flux; hence, narciclasine may be an effective and novel agent for the clinical treatment of sepsis-induced myocardial injury.

• Authors: Rong Tang, Liu Jia, Yunlong Li, Junbo Zheng, Pingping Qi
• Journal: Aging (Aging (Albany NY)) Vol. 13 Issue 11 Pg. 15151-15163 (05 25 2021) ISSN: 1945-4589 [Electronic] United States
• PMID: 34035183 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amaryllidaceae Alkaloids
• Lipopolysaccharides
• Phenanthridines
• narciclasine
• 3-methyladenine
• Adenine

Topics

• Adenine (analogs & derivatives, pharmacology, therapeutic use)
• Amaryllidaceae Alkaloids (pharmacology, therapeutic use)
• Animals
• Autophagy (drug effects)
• Inflammation (pathology)
• Lipopolysaccharides
• MAP Kinase Signaling System (drug effects)
• Male
• Mice, Inbred C57BL
• Myocardial Infarction (drug therapy, pathology)
• Myocardium (pathology)
• Myocytes, Cardiac (drug effects, pathology)
• Phenanthridines (pharmacology, therapeutic use)
• Sepsis (complications)
• Up-Regulation (drug effects)