title: Hexane fraction from Laminaria japonica exerts anti-inflammatory effects on lipopolysaccharide-stimulated RAW 264.7 macrophages via inhibiting NF-kappaB pathway.
abstract: OBJECTIVE
  Laminaria japonica is a representative marine brown alga used as a culinary item in East Asia. L. japonica extract was shown to exert various biological activities; however, its anti-inflammatory activity has not been reported. The aim of this study is to investigate the molecular mechanisms underlying its anti-inflammatory action.
  
  
  METHODS
  Anti-inflammatory mechanisms of L. japonica                   n-hexane fraction (LHF) were assessed using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. An anti-inflammatory compound isolated from LHF by reverse-phase chromatography was identified using nuclear magnetic resonance (NMR) spectroscopy.
  
  
  RESULTS
  Our results indicate that LHF significantly inhibited LPS-stimulated nitric oxide (NO) and prostaglandin E(2) (PGE(2)) secretion in a dose-dependent manner and suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) with no cytotoxicity. As results, levels of pro-inflammatory cytokines were significantly reduced by pretreatment of LHF in LPS-stimulated RAW 264.7 cells. Treatment of LHF strongly suppressed nuclear factor-κB (NF-κB) promoter-driven expression and nuclear translocation of NF-κB by preventing proteolytic degradation of inhibitor of κB (IκB)-α in LPS-stimulated RAW 264.7 cells. Moreover, LHF inhibited the phosphorylation of Akt and mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW 264.7 cells. One of the anti-inflammatory compounds was isolated from LHF and identified as fucoxanthin.
  
  
  CONCLUSIONS
  These results indicate that the LHF-mediated inhibition of NO and PGE(2) secretion in LPS-stimulated macrophages is regulated by NF-κB inactivation through inhibition of IκB-α, MAPKs, and Akt phosphorylation. LHF may be considered as a functional food candidate for the prevention or treatment of inflammatory diseases.
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, 599-1, Daeyeon-dong, Nam-gu, Busan, 608-737, South Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Min-Sup
authors.initials: MS
authors.lastname: Lee
authors.forename: Hee-Jeon
authors.initials: HJ
authors.lastname: Choi
authors.forename: Ji-Woong
authors.initials: JW
authors.lastname: Choi
authors.forename: Taisun
authors.initials: T
authors.lastname: Shin
authors.forename: Hee-Chul
authors.initials: HC
authors.lastname: Woo
authors.forename: Jae-Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Hyeung-Rak
authors.initials: HR
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology*; D045744:Cell Line, Tumor; D056148:Chromatography, Reverse-Phase; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D005786:Gene Expression Regulation; D006586:Hexanes; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007795:Laminaria / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D016207:Cytokines; D006586:Hexanes; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D024341:Xanthophylls; C025164:fucoxanthin; D000072000:NF-KappaB Inhibitor alpha; C026385:n-hexane; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases