The flavonoid-enriched fraction AF4 suppresses neuroinflammation and promotes restorative gene expression in a mouse model of experimental autoimmune encephalomyelitis.
The anti-inflammatory and restorative effects of the flavonoid-enriched fraction AF4 were examined in a mouse model of experimental autoimmune encephalomyelitis (EAE). Relative to EAE mice that received vehicle (water, 10 ml/kg/day), oral administration of AF4 (25mg/kg/day) beginning 24h after the onset of clinical signs reduced disease severity from days 19-31 post-immunization. AF4-mediated recovery from EAE was preceded by reduced plasma concentrations of TNFα and IL-1β on day 18 followed by decreased cytokine production and neuropathology in the cerebellum and spinal cord on day 31. Clinical improvement for EAE-AF4 mice from days 18 to 31 was accompanied by the elevated expression of genes that mediate remyelination. These findings suggest that AF4 decreased EAE severity by promoting the resolution of inflammation and improving functional recovery in the CNS.
Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Jordan
J
Warford
Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Quinton R D
QR
Jones
Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Matthew
M
Nichols
Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Victoria
V
Sullivan
Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, Nova Scotia, Canada.
H P Vasantha
HP
Rupasinghe
Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Psychiatry, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: George.Robertson@dal.ca.
George S
GS
Robertson
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002853:Chromatography, Liquid; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D007150:Immunohistochemistry; D027845:Malus / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D053719:Tandem Mass Spectrometry
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005419:Flavonoids; D010936:Plant Extracts
Chemokine; Cytokine; Multiple sclerosis; Polyphenolic; Remyelination