A synthetic chalcone derivative, compound 39, alleviates lipopolysaccharide-induced acute lung injury in mice

Our research group has previously synthesized various chalcone analogues. Of these analogues, compound 39 has been shown to exhibit potent antioxidative activities but its anti-inflammatory and anti-apoptosis effects remain unclear. Thus, the present study investigated the in vivo and in vitro effects and mechanisms of compound 39 in lipopolysaccharide (LPS)-induced acute lung injury (ALI). To induce ALI, the mice received LPS via a tracheal instillation 6 h after intragastric administration of compound 39 or vehicle. Histological changes, the lung wet/dry weight ratio, and the amounts of protein and inflammatory cells in the broncho-alveolar lavage (BAL) fluid were assessed after 24 h. Additionally, to determine its underlying mechanisms, Western blot and immunofluorescence analyses were used. Moreover, the in vitro effects of compound 39 were also investigated. In the in vivo experiment, compound 39 markedly alleviated histopathological alterations, lung edema, and protein leakage, and exhibited potent anti-inflammatory effects. In the in vitro experiments, compound 39 dose-dependently reduced the levels of pro-inflammatory cytokines and reactive oxygen species. The results suggested that the anti-inflammatory effects of compound 39 were due to suppression of the mitogen-activated protein kinase (MAPK)/nuclear factor κB (NF-κB) pathway. Compound 39 also enhanced the protein levels of Bcl-2 and reduced the protein levels of Bax and cleaved caspase-3. The present study confirmed the anti-inflammatory, oxy-radical prohibitive, and anti-apoptosis activities of compound 39 against LPS-induced tissue and cell damage, and revealed the mechanisms underlying those processes.