title: Anti-inflammatory effect of unsaturated fatty acids and Ergosta-7,22-dien-3-ol from Marthasterias glacialis: prevention of CHOP-mediated ER-stress and NF-κB activation.
abstract: There has been increasing awareness to the potential interest of drug discovery from marine natural products to treat several pathological conditions, including inflammation. In this work we describe the anti-inflammatory activity of several compounds present in the echinoderm Marthasterias glacialis (spiny sea-star), using the inflammatory model RAW 264.7 cells challenged with LPS. Lipidomic profiling of the organism revealed two major classes of compounds: fatty acids and sterols. Among these, the predominant compounds cis 11-eicosenoic and cis 11,14 eicosadienoic acids and the unsaturated sterol ergosta-7,22-dien-3-ol were evaluated. The mechanism of action of the compounds was distinct as they modulated different levels of the inflammation pathway. Classical inflammatory markers, such as COX-2, iNOS, IL-6 and NF-κB, were evaluated. We also studied the contribution of the CHOP pathway-mediated ER-stress to the inflammatory process. Overall, the sterol ergosta-7,22-dien-3-ol was the most active compound, however maximum activity was obtained when all compounds were tested in combination, thus suggesting a potentially synergistic activity of both classes of metabolites. This work establishes the echinoderm M. glacialis as an interesting source of anti-inflammatory molecules.
authors.affiliation: REQUIMTE/Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
authors.forename: David M
authors.initials: DM
authors.lastname: Pereira
authors.affiliation: Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal ; IBMC -Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Georgina
authors.initials: G
authors.lastname: Correia-da-Silva
authors.affiliation: REQUIMTE/Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Valentão
authors.affiliation: Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal ; IBMC -Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Natércia
authors.initials: N
authors.lastname: Teixeira
authors.affiliation: REQUIMTE/Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
authors.forename: Paula B
authors.initials: PB
authors.lastname: Andrade
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000517:prevention & control; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013215:Starfish / Q000737:chemistry*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C497250:Ddit3 protein, mouse; D005229:Fatty Acids, Monounsaturated; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051742:Transcription Factor CHOP; C059438:ergosta-7,22-dien-3-ol; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C572289:eicosenoic acid; D004875:Ergosterol