title: Fucosterol isolated from Undaria pinnatifida inhibits lipopolysaccharide-induced production of nitric oxide and pro-inflammatory cytokines via the inactivation of nuclear factor-κB and p38 mitogen-activated protein kinase in RAW264.7 macrophages.
abstract: It has been reported that fucosterol has anti-diabetic, anti-oxidant, and anti-osteoporotic effects. We investigated the anti-inflammatory effects and the underlying molecular mechanism of fucosterol in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Fucosterol suppressed the expressions of inducible nitric oxide synthase (iNOS), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) by downregulating their transcriptions, and subsequently inhibited the productions of nitric oxide, TNF-α, and IL-6. In addition, fucosterol attenuated LPS-induced DNA binding and the transcriptional activity of nuclear factor-κB (NF-κB). These reductions were accompanied by parallel reductions in the phosphorylation and nuclear translocation of NF-κB. Furthermore, fucosterol attenuated the phosphorylations of mitogen-activated protein kinase kinases 3/6 (MKK3/6) and mitogen-activated protein kinase-activated protein kinase 2 (MK2), which are both involved in the p38 MAPK pathway. These results suggest that the anti-inflammatory effects of fucosterol are associated with the suppression of the NF-κB and p38 MAPK pathways.
authors.affiliation: Department of Pharmaceutical Biochemistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Min-Sang
authors.initials: MS
authors.lastname: Yoo
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Shin
authors.forename: Hye-Eun
authors.initials: HE
authors.lastname: Choi
authors.forename: Young-Wuk
authors.initials: YW
authors.lastname: Cho
authors.forename: Myun-Ho
authors.initials: MH
authors.lastname: Bang
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Baek
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology*; D013265:Stigmasterol / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D044648:Undaria / Q000737:chemistry*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000276:immunology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; C015896:fucosterol; D013265:Stigmasterol; D048051:p38 Mitogen-Activated Protein Kinases