Pectolinarigenin Attenuates LPS-Induced Lung Inflammation and Injury with Reduced HDAC3/NF-κB/NLRP3 Signaling

Pectolinarigenin (PEC), a naturally occurring flavonoid, exhibits anti-inflammatory and antioxidant activities in various experimental models. However, its protective effects against lipopolysaccharide (LPS)-induced lung inflammation and the underlying molecular mechanisms remain unclear. This study investigated the protective effects of PEC using LPS-treated MLE12 cells and RAW264.7 macrophages, as well as a prophylactic mouse model in which PEC was administered before LPS exposure. In LPS-treated MLE12 cells and RAW264.7 macrophages, PEC reduced inflammatory responses and cellular injury, accompanied by decreased reactive oxygen species production and modulation of the histone deacetylase 3 (HDAC3)/nuclear factor κB (NF-κB)/NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) signaling. Consistent with these findings, PEC pretreatment attenuated pulmonary edema, inflammatory cell infiltration, pro-inflammatory cytokine production, oxidative stress, pyroptosis-associated signaling, and histopathological lung injury in LPS-exposed mice. These protective effects were accompanied by reduced HDAC3 expression and nuclear localization, together with reduced NF-kB/NLRP3 signaling in lung tissues. Overall, PEC attenuated LPS-induced lung inflammation and injury, accompanied by reduced oxidative stress and modulation of HDAC3/NF-κB/NLRP3 signaling. These findings support the potential of PEC as a preventive agent against excessive pulmonary inflammation.