Long-term naringin consumption reverses a glucose uptake defect and improves cognitive deficits in a mouse model of Alzheimer's disease

Naringin, a bioflavonoid, has been reported to have potent neuro-protective effects, but its preventive effects on amyloid-beta (A beta) induced, Alzheimer's disease (AD) related, cognitive impairment, and the underlying mechanisms of these effects have not been well characterised. Three-month-old APP(swe)/PS Delta E9 transgenic mice were randomly assigned to a vehicle group, two naringin (either 50 or 100 mg/kg/day) groups, or an Aricept (2 mg/kg/day) group. After 16 weeks of treatment, we observed beneficial effects of naringin (100 mg/kg/day), including lessening learning and memory deficits, improving locomotor activity, reducing scattered senile plaques, and ameliorating disturbances in brain energy metabolism. Furthermore, GSK-3 beta phosphorylation significantly increased in the naringin-treated (100 mg/kg/day) group. These findings suggest that a reduction in plaque burden and an increase in glucose uptake through the inhibition of GSK-3 beta activity may be one of the mechanisms by which naringin improves cognitive functioning in the APP(swe)/PS Delta E9 transgenic mouse model of Alzheimer's disease. (c) 2012 Elsevier Inc. All rights reserved.