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

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.