title: Flavonoids influence monocytic GTPase activity and are protective in experimental allergic encephalitis.
abstract: In the chronic disabling disease multiple sclerosis (MS), migration of monocytes across the blood-brain barrier is a crucial step in the formation of new lesions in the central nervous system (CNS). Infiltrating monocyte-derived macrophages secrete inflammatory mediators such as oxygen radicals, which contribute to axonal demyelination and damage, resulting in neurological deficits. Flavonoids are compounds occurring naturally in food, which scavenge oxygen radicals and have antiinflammatory properties. To investigate whether they might suppress clinical symptoms in MS, we treated rats sensitized for acute and chronic experimental allergic encephalomyelitis, an experimental model of MS, with flavonoids. We demonstrated that the flavonoid luteolin substantially suppressed clinical symptoms and prevented relapse when administered either before or after disease onset. Luteolin treatment resulted in reduced inflammation and axonal damage in the CNS by preventing monocyte migration across the brain endothelium. Luteolin influenced migration by modulating the activity of Rho GTPases, signal transducers involved in transendothelial migration. Oral administration of luteolin also significantly reduced clinical symptoms.
authors.affiliation: Dept. of Molecular Cell Biology and Immunology, VUMC, FdG, PO Box 7057, 1007 MB Amsterdam, Netherlands.
authors.forename: Jerome J A
authors.initials: JJ
authors.lastname: Hendriks
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Alblas
authors.forename: Susanne M A
authors.initials: SM
authors.lastname: van der Pol
authors.forename: Eric A F
authors.initials: EA
authors.lastname: van Tol
authors.forename: Christine D
authors.initials: CD
authors.lastname: Dijkstra
authors.forename: Helga E
authors.initials: HE
authors.lastname: de Vries
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006168:Guinea Pigs; D047311:Luteolin / Q000008:administration & dosage*; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D020741:rho GTP-Binding Proteins; D047311:Luteolin