Lancemaside A inhibits lipopolysaccharide-induced inflammation by targeting LPS/TLR4 complex.
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.
Joh
Eun-Ha
EH
Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Hoegi, Dongdaemun-ku, Seoul 130-701, Korea.
Kim
Dong-Hyun
DH
D000818:Animals; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D016207:Cytokines; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D012503:Saponins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C533150:lancemaside A; D000072000:NF-KappaB Inhibitor alpha; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase