Potential Application of Tetrahydroxystilbene Glucoside in the Treatment of Alzheimer’s Disease

Abstract

Current treatment strategies for Alzheimer’s disease are mainly symptomatic, development of disease-modifying therapies is urgent needed. Polygonum Multiflorum has been used in Traditional Chinese Medicine for long history in the treatment of dementia. Pharmacological studies suggested Polygonum Multiflorum could improve learning and memory ability in the Alzheimer’s disease models, and inhibit β-amyloid production. 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside(TSG) is one main bioactive stillbene glycoside of Polygonum Multiflorum. The role of TSG in the Alzheimer’s disease treatment has been investigated. TSG might antagonize acetylcholine deficiency and cognitive performance impairment in the animal models of Alzheimer’s disease. By using β-amyloid precursor protein transgenic mice, TSG ameliorated learning and memory functions associated with reduced formation of senile plaques and β-amyloid deposition, and inhibition of γ- secretase and α-synuclein. In β-amyloid injection rat models, TSG increased cognitive behavior performance, and prevented β-amyloid deposition and synaptic degeneration. In the D-galactose induced aging model, TSG improved ability of learning and memory in the mice, inhibited β-amyloid precursor protein and β-amyloid expressions. Learning and memory deterioration in aged animals was reformed by TSG intervention; its effects might be exerted through β-amyloid precursor protein pathway.  TSG was also shown to display antioxidant activity in vitro and in vivo. In conclusion, TSG has been demonstrated to improve cognitive performance of Alzheimer’s disease models through multiple targets strategies, and may be a future perspective in the development of Alzheimer’s disease therapy.