Ellagic acid protects from myelin-associated sphingolipid loss in experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE), the most common model for multiple sclerosis, is characterized by inflammatory cell infiltration into the central nervous system and demyelination. Previous studies have demonstrated that administration of some polyphenols may reduce the neurological alterations of EAE. In this work, we show that ellagic acid, a polyphenolic compound, is beneficial in EAE, most likely through stimulation of ceramide biosynthesis within the brain. EAE was induced in Lewis rats by injection of guinea-pig spinal cord tissue along with Freund's complete adjuvant containing Mycobacterium tuberculosis. Clinical signs first appeared at day 8 post-immunization and reached a peak within 3 days, coincident with reduction of myelin basic protein (MBP) in the cortex. Sphingolipids, the other major components of myelin, also decreased at the acute phase of EAE, both in the cerebral cortex and in the spinal cord. In rats receiving ellagic acid in the drinking water from 2 days before immunization, the onset of the disease was delayed and clinical signs were reduced. This amelioration of clinical signs was accompanied by sustained levels of both MBP and sphingolipid in the cortex, without apparent changes in infiltration of inflammatory CD3+ T-cells, microglial activation, or weight loss, which together suggest a neuroprotective effect of ellagic acid. Finally, in glioma and oligodendroglioma cells we demonstrate that urolithins, the ellagic acid metabolites that circulate in plasma, stimulate the synthesis of ceramide. Together these data suggest that ellagic acid consumption protects against demyelination in rats with induced EAE, likely by a mechanism involving sphingolipid synthesis.
['Busto|Rebeca|R|', 'Serna|Jorge|J|', 'Perianes-Cachero|Aránzazu|A|', 'Quintana-Portillo|Rocío|R|', 'García-Seisdedos|David|D|', 'Canfrán-Duque|Alberto|A|', 'Paino|Carlos L|CL|', 'Lerma|Milagros|M|', 'Casado|María E|ME|', 'Martín-Hidalgo|Antonia|A|', 'Arilla-Ferreiro|Eduardo|E|', 'Lasunción|Miguel A|MA|', 'Pastor|Óscar|Ó|']
D000818:Animals D000893:Anti-Inflammatory Agents D045744:Cell Line, Tumor D002518:Ceramides D002540:Cerebral Cortex D003374:Coumarins D004610:Ellagic Acid D004681:Encephalomyelitis, Autoimmune, Experimental D005260:Female D005620:Freund's Adjuvant D015870:Gene Expression D006168:Guinea Pigs D009169:Mycobacterium tuberculosis D004676:Myelin Basic Protein D009186:Myelin Sheath D009457:Neuroglia D018696:Neuroprotective Agents D009836:Oligodendroglia D051381:Rats D011917:Rats, Inbred Lew D013116:Spinal Cord
Ellagic acid Sphingolipids Experimental autoimmune encephalomyelitis Multiple sclerosis Polyphenols Myelin