title: Hexane fraction from Sargassum fulvellum inhibits lipopolysaccharide-induced inducible nitric oxide synthase expression in RAW 264.7 cells via NF-κB pathways.
abstract: Sargassum fulvellum (Turner) C. Agardh has been used to treat various inflammatory diseases, including lump, dropsy, swollen and painful scrotum, and urination problems for several centuries with no side effects. This study aims to investigate the anti-inflammatory effect of the hexane fraction of S. fulvellum (HFS) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and phorbol 12-myristate 13-acetate (PMA)-induced mouse-ear edema. The anti-inflammatory activity of HFS in LPS-stimulated RAW 264.7 cells was investigated by assessing the inhibition of nitric oxide (NO) and pro-inflammatory cytokine production during Griess reaction and enzyme-linked immunosorbent assay (ELISA), respectively. The molecular mechanisms that underlie the anti-inflammatory action of HFS were investigated by analyzing the activation of transcription factor and its upstream signaling proteins. Additionally, an in vivo study of the anti-inflammatory effect of HFS was carried out using PMA-induced mouse-ear edema. HFS inhibited LPS-induced NO production in a dose-dependent manner and suppressed the expression of inducible NO synthase (iNOS) in the RAW 264.7 cells. Further, HFS reduced the production of pro-inflammatory cytokines in the LPS-stimulated RAW 264.7 cells. HFS significantly inhibited LPS-induced nuclear factor kappa B (NF-κB) transcriptional activity and NF-κB translocation into the nucleus by preventing degradation of inhibitor κB-α. Moreover, HFS inhibited the activation of Akt and mitogen-activated protein kinases (MAPKs) in the LPS-stimulated RAW 264.7 cells. Furthermore, HFS suppressed PMA-induced mouse-ear edema. The above data indicate that the anti-inflammatory effects of HFS on LPS-stimulated cells are associated with the suppression of NF-κB through the inhibition of MAPKs and Akt phosphorylation.
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, South Korea.
authors.forename: Wi-Gyeong
authors.initials: WG
authors.lastname: Gwon
authors.forename: Min-Sup
authors.initials: MS
authors.lastname: Lee
authors.forename: Jong-Soon
authors.initials: JS
authors.lastname: Kim
authors.forename: Jae-Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Chi-Won
authors.initials: CW
authors.lastname: Lim
authors.forename: Nam-Gil
authors.initials: NG
authors.lastname: Kim
authors.forename: Hyeung-Rak
authors.initials: HR
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001692:Biological Transport; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004423:Ear; D004487:Edema / Q000188:drug therapy / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D044647:Sargassum; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases