Tulipalin A suppressed the pro-inflammatory polarization of M1 macrophage and mitigated the acute lung injury in mice via interference DNA binding activity of NF-κB.

Acute lung injury (ALI) is an inflammatory disorder accompanied by higher morbidity and mortality. The pathological mechanism of ALI has been reported to be associated with the release of inflammatory cytokines by macrophages. Sesquiterpene lactones (SLs) represent the principal anti-inflammatory components of many natural products. Tulipalin A is a natural small molecule and a conserved moiety in anti-inflammatory SLs. However, the anti-inflammatory potential of Tulipalin A has yet to be fully disclosed. The present study aims to investigate TulipalinA's anti-inflammatory activity and underlying mechanisms in vitro and in vivo. Tulipalin A suppressed inflammatory responses in lipopolysaccharide (LPS)-stimulated bone marrow-derived primary macrophages and ameliorated LPS-induced ALI in mice. Mechanistically, Tulipalin A directly targets the NF-κB p65 and disrupts its DNA binding activity, thereby impeding the activation of NF-κB. Inhibition of NF-κB attenuated M1 polarization of macrophages, consequently suppressing the production of pro-inflammatory mediators and ameliorating the onset and progression of ALI. These findings suggest Tulipalin A's potential to mitigate inflammatory disorders like ALI via targeting NF-κB p65 and disrupting its DNA binding activity.