Kurarinone exerts anti-inflammatory effect via reducing ROS production, suppressing NLRP3 inflammasome, and protecting against LPS-induced sepsis.

Abstract

Kurarinone, a major lavandulyl flavanone found in the roots of Sophora flavescens aiton, has been reported to exhibit anti-inflammatory and anti-oxidative activities in lipopolysaccharide (LPS)-induced macrophages; however, the effects of kurarinone on the activation of NLRP3 inflammasome and the protective effects against sepsis have not been well investigated. In this study, we aimed to investigate the impacts of kurarinone on NLRP3 inflammasome activation in lipopolysaccharide (LPS)-induced macrophages and its protective effects against sepsis in vivo. Secretion of pro-inflammatory cytokines, activation of MAPKs and NF-κB signaling pathways, formation of NLRP3 inflammasome, and production of reactive oxygen species (ROS) by LPS-induced macrophages were examined; additionally, in vivo LPS-induced endotoxemia model was used to investigate the protective effects of kurarinone in sepsis-induced damages. Our experimental results demonstrated that kurarinone inhibited the expression of iNOS and COX-2, suppressed the phosphorylation of MAPKs, attenuated the production of TNF-α, IL-6, nitric oxide (NO) and ROS, repressed the activation of the NLRP3 inflammasome, and impeded the maturation and secretion of IL-1β and caspase-1. Furthermore, the administration of kurarinone attenuated the infiltration of neutrophils in the lung, kidneys and liver, reduced the expression of organ damage markers, and increased the survival rate in LPS-challenged mice. Collectively, our study demonstrated that kurarinone can protect against LPS-induced sepsis damage and exert anti-inflammatory effects via inhibiting MAPK/NF-κB pathways, attenuating NLRP3 inflammasome formation, and preventing intracellular ROS accumulation, suggesting that kurarinone might have potential for treating sepsis and inflammation-related diseases.

• Authors: Taha Yazal, Po-Yen Lee, Pin-Rong Chen, I-Chen Chen, Po-Len Liu, Yuan-Ru Chen, Tzu-Chieh Lin, Yi-Ting Chen, Shu-Pin Huang, Hsin-Chih Yeh, Ching-Chih Liu, Jung Lo, Hsin-En Wu, Shu-Chi Wang, Chia-Yang Li
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 167 Pg. 115619 (Nov 2023) ISSN: 1950-6007 [Electronic] France
• PMID: 37804813 (Publication Type: Journal Article)
• Copyright: Copyright © 2023. Published by Elsevier Masson SAS.

Chemical References

• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Lipopolysaccharides
• kurarinone
• Reactive Oxygen Species
• NF-kappa B
• Anti-Inflammatory Agents

Topics

• Mice
• Animals
• Inflammasomes (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Lipopolysaccharides (toxicity)
• Reactive Oxygen Species (metabolism)
• NF-kappa B (metabolism)
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Sepsis (chemically induced, drug therapy)