Natural Docosahexaenoic Acid in the Triglyceride Form Attenuates In Vitro Microglial Activation and Ameliorates Autoimmune Encephalomyelitis in Mice

• Published in: Nutrients 2017-06, Vol.9 (7), p.681
• Main Authors: Mancera, Pilar, Wappenhans, Blanca, Cordobilla, Begoña, Virgili, Noemí, Pugliese, Marco, Rueda, Fèlix, Espinosa-Parrilla, Juan F, Domingo, Joan C
• Format: Article
• Language: English
• Subjects: animal models; Animals; anti-inflammatory activity; Anti-inflammatory agents; Biocompatibility; CD4 antigen; Cell Line; Cell Proliferation; Cell Survival - drug effects; Chemical compounds; cytokines; Cytokines - genetics; Cytokines - metabolism; Docosahexaenoic acid; Docosahexaenoic Acids - pharmacology; encephalitis; Encephalomyelitis, Autoimmune, Experimental - chemically induced; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Estrès oxidatiu; Experimental allergic encephalomyelitis; humans; in vitro studies; Inflammation; Inflammation - metabolism; Interferon; interferon-gamma; Lipopolysaccharides; lymphocyte proliferation; Lymphocytes - drug effects; Mice; Microglia; Microglia - drug effects; Micròglia; Myelin-Oligodendrocyte Glycoprotein - toxicity; neurodegenerative diseases; neuroglia; Nitric Oxide; omega-3 fatty acids; Oxidative stress; Pharmacology; Polyunsaturated fatty acids; Rodents; Spleen - cytology; splenocytes; therapeutics; Toxicity; triacylglycerols; γ-Interferon
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu9070681

Many neurodegenerative diseases are associated, at least in part, to an inflammatory process in which microglia plays a major role. The effect of the triglyceride form of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (TG-DHA) was assayed in vitro and in vivo to assess the protective and anti-inflammatory activity of this compound. In the in vitro study, BV-2 microglia cells were previously treated with TG-DHA and then activated with Lipopolysaccharide (LPS) and Interferon-gamma (IFN-γ). TG-DHA treatment protected BV-2 microglia cells from oxidative stress toxicity attenuating NO production and suppressing the induction of inflammatory cytokines. When compared with DHA in the ethyl-ester form, a significant difference in the ability to inhibit NO production in favor of TG-DHA was observed. TG-DHA inhibited significantly splenocyte proliferation but isolated CD4+ lymphocyte proliferation was unaffected. In a mice model of autoimmune encephalomyelitis (EAE), 250 mg/kg/day oral TG-DHA treatment was associated with a significant amelioration of the course and severity of the disease as compared to untreated animals. TG-DHA-treated EAE mice showed a better weight profile, which is a symptom related to a better course of encephalomyelitis. TG-DHA may be a promising therapeutic agent in neuroinflammatory processes and merit to be more extensively studied in human neurodegenerative disorders.