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

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.