lancemaside-a and Inflammation

In this study, we aimed to examine the cellular and molecular mechanisms of lancemaside A from Codonopsis lanceolata (Campanulaceae) in the inflammatory responses of monocytes (U937 cells) and macrophages (RAW264.7 cells). Lancemaside A significantly suppressed the inflammatory functions of lipopolysaccharide- (LPS-) treated RAW264.7 cells by suppressing the production of nitric oxide (NO), the expression of the NO-producing enzyme inducible NO synthase (iNOS), the upregulation of the costimulatory molecule CD80, and the morphological changes induced by LPS exposure. In addition, lancemaside A diminished the phagocytic activity of RAW264.7 cells and boosted the neutralizing capacity of these cells when treated with the radical generator sodium nitroprusside (SNP). Interestingly, lancemaside A strongly blocked the adhesion activity of RAW264.7 cells to plastic culture plates, inhibited the cell-cell and cell-fibronectin (FN) adhesion of U937 cells that was triggered by treatment with an anti-β1-integrin (CD29) antibody and immobilized FN, respectively. By evaluating the activation of various intracellular signaling pathways and the levels of related nuclear transcription factors, lancemaside A was found to block the activation of inhibitor of κB kinase (IKK) and p65/nuclear factor- (NF-) κB. Taken together, our findings strongly suggest that the anti-inflammatory function of lancemaside A is the result of its strong antioxidative and IKK/NF-κB inhibitory activities.

Topics: Animals; Antioxidants; Cell Adhesion; Cell Line; Cell Survival; Codonopsis; Humans; I-kappa B Kinase; Inflammation; Integrin beta1; Lipopolysaccharides; Macrophages; Mice; Monocytes; Nitric Oxide; Nitroprusside; Phagocytosis; Saponins; U937 Cells

In our previous study, lancemaside A isolated from Codonopsis lanceolata (family Campanulaceae) ameliorated colitis in mice. In this study, the anti-inflammatory effects of lancemaside A was investigated in lipopolysaccharide (LPS)-stimulated mice and their peritoneal macrophage cells. Lancemaside A suppressed the production of pro-inflammatory cytokines, TNF-α and IL-1β, in vitro and in vivo. Lancemaside A also down-regulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the inflammatory mediators, nitric oxide (NO), and PGE(2). Lancemaside A also inhibited the expression of IL-1 receptor-associated kinase-4 (IRAK-4), the phosphorylation of IKK-β and IκB-α, the nuclear translocation of NF-κB and the activation of mitogen-activated protein kinases in LPS-stimulated peritoneal macrophages. Furthermore, lancemaisde A inhibited the interaction between LPS and TLR4, as well as IRAK-4 expression in peritoneal macrophages. Based on these findings, lancemaside A expressed anti-inflammatory effects by regulating both the binding of LPS to TLR4 on macrophages.

Topics: Animals; Cyclooxygenase 2; Cytokines; I-kappa B Kinase; I-kappa B Proteins; Inflammation; Inflammation Mediators; Lipopolysaccharides; Macrophage Activation; Macrophages, Peritoneal; Male; Mice; Mice, Inbred ICR; NF-kappa B; NF-KappaB Inhibitor alpha; Nitric Oxide Synthase Type II; Phosphorylation; Protein Binding; Protein Processing, Post-Translational; Saponins; Toll-Like Receptor 4