Neuroprotective Effects of a Novel Apple Peel Extract AF4 in a Mouse Model of Hypoxic-Ischemic Brain Injury

Abstract

The neuroprotective effects of AF4, a flavonoid-enriched extract derived from the peel of Northern Spy apples (containing quercetin-3-O-glucoside, quercetin-3-O-galactoside, quercetin-3-O-rhamnoside, quercetin-3-O-rutinoside, epicatechin, and cyanidin-3-O-galactoside) were examined by assessing neuronal loss and motor impairment resulting from hypoxic-ischemic (HI) brain injury in adult C57BL/6 mice. Relative to vehicle treatment (water, 10mL/kg/day), oral administration of AF4 (50 mg/kg/day) for 3 days reduces HI-induced neuronal loss in the striatum and hippocampus, motor impairments, and reduces the ability of LPS to stimulate the production of TNF-alpha in whole blood. Pretreatment with AF4 (1 ug/mL) decreased the death of mouse primary cortical neurons subjected to oxygen glucose deprivation (12 hours) in comparison to vehicle (DMSO) or the same concentration of quercetin or its metabolites. Taken together these findings indicate that AF4 reduces HI-induced brain injury and motor deficits by increasing the resistance of vulnerable neurons to ischemic cell death and decreasing the production of inflammatory cytokines.