title: 6,6'-Bieckol, isolated from marine alga Ecklonia cava, suppressed LPS-induced nitric oxide and PGE₂ production and inflammatory cytokine expression in macrophages: the inhibition of NFκB.
abstract: Ecklonia cava is an edible brown alga that contains high levels of phlorotannins, which are unique marine polyphenolic compounds. In the present study, we investigated the anti-inflammatory effects and the underlying molecular mechanism of phlorotannin 6,6'-bieckol, which is an active component isolated from E. cava, on lipopolysaccharide (LPS)-stimulated primary macrophages and RAW 264.7 macrophage cells. 6,6'-Bieckol was found to inhibit nitric oxide (NO) and prostaglandin E₂ (PGE₂) production and to suppress the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, 6,6'-bieckol downregulated the production and mRNA expression of the inflammatory cytokines TNF-α and IL-6. Moreover, pretreatment with 6,6'-bieckol decreased LPS-induced transactivation of nuclear factor-kappa B (NFκB) and nuclear translocation of p50 and p65 subunits of NFκB. Furthermore, chromatin immunoprecipitation assay revealed that 6,6'-bieckol inhibited LPS-induced NFκB binding to the TNF-α and IL-6 promoters. Taken together, these data suggest that the anti-inflammatory properties of 6,6'-bieckol are related to the down-regulation of iNOS, COX-2, and pro-inflammatory cytokines through the negative regulation of the NFκB pathway in LPS-stimulated macrophages.
authors.affiliation: Department of Life & Nanopharmaceutical Science, Kyung Hee University, Seoul, South Korea.
authors.forename: Yeong-In
authors.initials: YI
authors.lastname: Yang
authors.forename: Hyeon-Cheol
authors.initials: HC
authors.lastname: Shin
authors.forename: Seong Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
authors.forename: Jung-Hye
authors.initials: JH
authors.lastname: Choi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D004147:Dioxins / Q000302:isolation & purification / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D000459:Phaeophyceae / Q000737:chemistry*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D004147:Dioxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D012313:RNA; C062360:6,6'-bieckol; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone