title: Two enone fatty acids isolated from Gracilaria verrucosa suppress the production of inflammatory mediators by down-regulating NF-kappaB and STAT1 activity in lipopolysaccharide-stimulated RAW 264.7 cells.
abstract: Gracilaria verrucosa is a common marine red alga that has anti-oxidant and anti-cancer properties. Recently, we reported that anti-inflammatory constituents of G. verrucosa operate through an unknown mechanism. For this reason, we isolated two enone fatty acids from G. verrucosa and investigated their molecular mechanism in LPS-stimulated RAW264.7 cells. We found that the two compounds inhibited the production of inflammatory markers (nitric oxide, TNF-alpha, and IL-6) in a dose-dependent manner. We next studied the effects of G. verrucosa compounds on LPS-induced signaling pathways. The two compounds suppressed NF-kappaB reporter activity by interfering with nuclear translocation of NF-kappaB and suppressed JAK/STAT (p-STAT1) signaling. These results suggest that G. verrucosa inhibits the production of inflammatory mediators (NO, TNF-alpha, and IL-6) by suppressing the activation of NF-kappaB and the phosphorylation of STAT1.
authors.affiliation: Department of Pharmacology, College of Medicine, Jeju National University, Jeju, 690-756, Korea.
authors.forename: Hye-Ja
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hung-The
authors.initials: HT
authors.lastname: Dang
authors.forename: Gyeoung-Jin
authors.initials: GJ
authors.lastname: Kang
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Yang
authors.forename: Sun-Soon
authors.initials: SS
authors.lastname: Park
authors.forename: Weon-Jong
authors.initials: WJ
authors.lastname: Yoon
authors.forename: Jee H
authors.initials: JH
authors.lastname: Jung
authors.forename: Hee-Kyoung
authors.initials: HK
authors.lastname: Kang
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Yoo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005227:Fatty Acids / Q000302:isolation & purification / Q000494:pharmacology*; D044724:Gracilaria / Q000737:chemistry; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005227:Fatty Acids; D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; C498144:Rela protein, mouse; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D053612:Janus Kinases