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Corylifol a alleviates lipopolysaccharide-induced inflammation by targeting and inhibiting IκBα phosphorylation

Yanxuan Hu, Xiangrong Feng, Xibao Zhao, Xucan Huang, Yunjian Wang, Yufeng Fu, Yue Xiao, Han Wu, Qianqian Di

Journal:INTERNATIONAL IMMUNOPHARMACOLOGY

IF:5.6

DOI:10.1016/j.intimp.2026.117203

PMID:

Published:2026-07-29

research field:神经科学分子生物学细胞生物学干细胞生物学神经退行性疾病遗传学与基因组学

Abstract

Endotoxemia is an inflammatory disorder triggered by endotoxins derived from pathogenic bacteria. To identify effective anti-inflammation agents, we screened a chemical compound library and identified Corylifol A as a potent suppressor of LPS-induced inflammation. Corylifol A is a natural flavonoid compound originally isolated from Psoralea corylifolia . Further investigations revealed that Corylifol A dose-dependently inhibited LPS-induced expression of IL-1β, TNF-α, and IL-6 in macrophages, without exhibiting cytotoxicity. Mechanistically, Corylifol A directly bound to IκBα, disrupted IKKβ-IκBα interaction, suppressed IκBα phosphorylation, and subsequently blocked p65 nuclear translocation. In vivo, both prophylactic and therapeutic administration of Corylifol A significantly improved survival rates, reduced inflammatory cytokine levels, and attenuated lung injury in endotoxic mice. Collectively, our findings demonstrate that Corylifol A protects against endotoxemia by targeting IκBα and inhibiting NF-κB activation, highlighting its therapeutic potential for the treatment of endotoxemia and related inflammatory diseases.

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