sauchinone and Acute-Lung-Injury

Previous studies have shown that sauchinone modulates the expression of inflammatory mediators through mitogen-activated protein kinase (MAPK) pathways in various cell types. However, little information exists about the effect of sauchinone on neutrophils, which play a crucial role in inflammatory process such as acute lung injury (ALI). We found that sauchinone decreased the phosphorylation of p38 MAPK in lipopolysaccharide (LPS)-stimulated murine bone marrow neutrophils, but not ERK1/2 and JNK. Exposure of LPS-stimulated neutrophils to sauchinone or SB203580, a p38 inhibitor, diminished production of tumor necrosis factor (TNF)-α and macrophage inflammatory protein (MIP)-2 compared to neutrophils cultured with LPS. Treatment with sauchinone decreased the level of phosphorylated ribosomal protein S6 (rpS6) in LPS-stimulated neutrophils. Systemic administration of sauchinone to mice led to reduced levels of phosphorylation of p38 and rpS6 in mice lungs given LPS, decreased TNF-α and MIP-2 production in bronchoalveolar lavage fluid, and also diminished the severity of LPS-induced lung injury, as determined by reduced neutrophil accumulation in the lungs, wet/dry weight ratio, and histological analysis. These results suggest that sauchinone diminishes LPS-induced neutrophil activation and ALI.

Topics: Acute Lung Injury; Animals; Benzopyrans; Cell Movement; Cells, Cultured; Chemokine CXCL2; Cytokines; Dioxoles; Inflammation Mediators; Lignans; Lipopolysaccharides; Macrophages; Male; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Neutrophils; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Ribosomal Protein S6; Saururaceae; Tumor Necrosis Factor-alpha