Crotalaria ferruginea extract attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting MAPK/NF-κB signaling pathways

Objective: To evaluate the anti-inflammatory activity of Crotalaria ferruginea extract(CFE) and its mechanism.Methods: An intratracheal lipopolysaccharide(LPS) instillationinduced acute lung injury(ALI) model was used to study the antiinflammatory activity of CFE in vivo. The LPS-induced shock model was used to analyze the effect of CFE on survival. LPS-stimulated RAW264.7 cell model was used to investigate the anti-inflammatory activity of CFE in vitro and the effects on mitogen-activated protein kinase(MAPK) or nuclear factor-κB(NF-κB) signaling pathways.Results: CFE administration decreased the number of inflammatory cells, reduced the levels of tumor necrosis factor-α(TNF-α),monocyte chemotactic protein-1(MCP-1), interleukin-6(IL-6), and interferon-γ, and diminished protein content in the bronchoalveolar lavage fluid of mice. CFE also reduced lung wet-to-dry weight ratio,myeloperoxidase, and lung tissue pathological injury. CFE preadministration improved the survival rate of mice challenged with a lethal dose of LPS. CFE reduced LPS-activated RAW264.7 cells to produce nitric oxide, TNF-α, MCP-1, and IL-6. Furthermore, CFE inhibited nuclear translocation and phosphorylation of NF-κB P65,extracellular signal-regulated kinase, c-Jun N-terminal kinases, and P38 MAPKs.Conclusions: CFE exhibits potent anti-inflammatory activity in LPS-induced ALI mice, LPS-shock mice, and RAW264.7 cells, and its mechanism may be associated with the inhibition of NF-κB and MAPK signaling pathways. Crotalaria ferruginea may be a useful therapeutic drug for the treatment of ALI and other respiratory inflammations.