Lancemaside A inhibits lipopolysaccharide-induced inflammation by targeting LPS/TLR4 complex

Abstract

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.