The flavonoid-enriched fraction AF4 suppresses neuroinflammation and promotes restorative gene expression in a mouse model of experimental autoimmune encephalomyelitis

•AF4 is a flavonoid-enriched fraction derived from apple peel.•Oral AF4 dosing reduced the severity of experimental autoimmune encephalomyelitis.•AF4 decreased pro-inflammatory cytokine production in plasma and spinal cord.•AF4 reduced plasma TNF-α and IL-β levels before resolving neuroinflammation.•AF4 elevated the expression of genes in the spinal cord that mediate remyelination.

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 (25 mg/kg/day) beginning 24 h 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.