Rutaecarpine ameliorated high sucrose-induced Alzheimer's disease like pathological and cognitive impairments in mice

High sucrose can induce tau hyperphosphorylation and cognitive dysfunction/memory impairment as observed in Alzheimer's disease (AD). Rutaecarpine, a specific (Transient receptor potential vanilloid 1, TRPV1) agonist, is neuroprotective against high sucrose diet induced impairment, but the detailed mechanisms are still elusive. In this study, we investigated whether rutaecarpine mitigates high sucrose diet-induced pathological alterations and cognitive in AD-like mice. The mice were administered withfodder contain 0.01% rutaecarpine and 20% sucrose solution.Our results showed that rutaecarpine significantly attenuated high sucrose diet induced spatial memory impairment and enhanced synaptic plasticity; Rtaecarpine prevented high sucrose diet induced tau hyperphosphorylation by decreasing (Glycogen synthase kinase-3β, GSK-3β) activity; Activation of GSK-3β reversed the protective effect of rutaecarpine on learning and memory deficits, synaptic plasticity and tau hyperphosphorylation induced by high glucose diet significantly, suggesting that GSK-3β activation is required for high glucose induced tau hyperphosphorylation. These results demonstrated that rutaecarpine can mitigate high sucrose diet induced hyperphosphorylation of AD-associated tau protein and cognitive impairment by inhibiting GSK-3β, Which supported that dietary rutaecarpine might have a promising use for for therapeutic intervention of AD.