title: Britanin suppresses LPS-induced nitric oxide, PGE2 and cytokine production via NF-κB and MAPK inactivation in RAW 264.7 cells.
abstract: Little is known about the biological properties of britanin, which is isolated from the flowers of Inula japonica (Inulae Flos). Based on our previous studies that Inulae Flos had anti-inflammation and anti-asthmatic activities, we tried to find the bioactive compounds from it. In this study, the anti-inflammatory effects of britanin on the inflammatory mediators as well as on nuclear factor (NF)-кB and mitogen-activated protein (MAP) kinase activation were evaluated in RAW 264.7 cells. Britanin inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) along with the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In addition, britanin reduced the release of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6. Furthermore, the phosphorylations of MAP kinases (p38 and JNK) in LPS-stimulated RAW 264.7 cells were suppressed by britanin. Moreover, britanin inhibited the NF-κB activation induced by LPS, which was associated with the abrogation of IκBα degradation and subsequent decreases in nuclear p65 levels. This study suggests that the anti-inflammatory activities of britanin might be attributed to the inhibition of iNOS and COX-2 and cytokine expression at least in part, through the attenuation of the phosphorylations of MAP kinases and NF-κB activation via IκBα degradation in macrophages. We conclude that britanin may have potential for the treatment of inflammatory diseases through the down-regulation of MAP kinases and NF-κB mediated activation of macrophages.
authors.affiliation: Research and Development Division, Korean Promotion Institute for Traditional Medicine Industry, Gyeongsan 712-210, South Korea.
authors.forename: Hyo-Hyun
authors.initials: HH
authors.lastname: Park
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Kim
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Young Na
authors.initials: YN
authors.lastname: Park
authors.forename: Jiean
authors.initials: J
authors.lastname: Lee
authors.forename: Youn Ju
authors.initials: YJ
authors.lastname: Lee
authors.forename: Sun-Gun
authors.initials: SG
authors.lastname: Kim
authors.forename: Hyun-Je
authors.initials: HJ
authors.lastname: Park
authors.forename: Jong Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Hyeun Wook
authors.initials: HW
authors.lastname: Chang
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Lee
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D038143:Inula / Q000276:immunology; D007783:Lactones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D018836:Inflammation Mediators; D007783:Lactones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012717:Sesquiterpenes; C575454:britannin; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone