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Geniposide protects against sepsis-induced myocardial dysfunction through AMPKα-dependent pathway.

Geniposide protects against sepsis-induced myocardial dysfunction through AMPKα-dependent pathway.

Authors :
Song P
Shen DF
Meng YY
Kong CY
Zhang X
Yuan YP
Yan L
Tang QZ
Ma ZG
Source :
Free radical biology & medicine [Free Radic Biol Med] 2020 May 20; Vol. 152, pp. 186-196. Date of Electronic Publication: 2020 Feb 17.
Publication Year :
2020

Abstract

Uncontrolled inflammatory response and subsequent cardiomyocytes loss (apoptosis and pyroptosis) are closely involved in sepsis-induced myocardial dysfunction. Our previous study has found that geniposide (GE) can protect the murine hearts against obesity-induced inflammation. However, the effect of GE on sepsis-related cardiac dysfunction is still unknown. Mice were exposed to lipopolysaccharide (LPS) to generate sepsis-induced myocardial dysfunction. And 50 mg/kg GE was used to treat mice for consecutive 7 days. Our results showed that GE treatment significantly improved survival rate and cardiac function, and suppressed myocardial inflammatory response, as well as myocardial loss in LPS-treated mice. Those effects of GE were largely abolished in NOD-like receptor protein 3 (NLRP3)-deficient mice. Further detection revealed that the inhibition of NLRP3 inflammasome activation depended on the reduction of p47phox by GE. GE treatment restored the phosphorylation and activity of AMP-activated protein kinase α (AMPKα) in the hearts of sepsis mice, and knockout of AMPKα abolished the protection of GE against reactive oxygen species (ROS) accumulation, NLRP3 inflammasome activation and cardiomyocytes loss in sepsis mice. In conclusion, our findings revealed that GE activated AMPKα to suppress myocardial ROS accumulation, thus blocking NLRP3 inflammasome-mediated cardiomyocyte apoptosis and pyroptosis and improving cardiac function in mice with sepsis.<br />Competing Interests: Declaration of competing interest None.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1873-4596
Volume :
152
Database :
MEDLINE
Journal :
Free radical biology & medicine
Publication Type :
Academic Journal
Accession number :
32081748
Full Text :
https://doi.org/10.1016/j.freeradbiomed.2020.02.011