Tetrahydroxy Stilbene Glucoside Ameliorates Cognitive Impairments and Pathology in APP/PS1 Transgenic Mice

Cognitive impairment is the main clinical manifestation of Alzheimer's disease(AD),and amyloid-β(AB)deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains.This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside(TSG)on cognitive function in APP/PS 1 mice during long-term administration.Here,we treated APP/PS1 model mice of AD with different doses of TSG(50 mg/kg and 100 mg/kg)for 5 to 17 months by gavage,and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests,and investigated the possible mechanisms by immunohistochemistry and Western blotting.Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test.Furthermore,Aβ40/42 deposition in the cortex and hippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique.Finally,Western blotting showed that TSG primarily decreased the APP expression to avoid the Aβplaque deposition in the cortex and hippocampus of mice.These results reveal the beneficial effects of TSG in APP/PSI-AD mice,which may be associated with the reduction of Aβdeposits in the brain.

Protective effect of tetrahydroxy stilbene glucoside on learning and memory by regulating synaptic plasticity

Damage to synaptic plasticity induced by neurotoxicity of amyloid-beta is regarded to be one of the pathological mechanisms of learning and memory disabilities in Alzheimer＇s disease patients. This study assumed that the damage of amyloid-beta to learning and memory abilities was strongly associated with the changes in the Fyn/N-methyl-D-aspartate receptor 2B （NR2B） expression. An APP695V7171 transgenic mouse model of Alzheimer＇s disease was used and treatment with tetrahydroxy-stilbene glucoside was administered intragas- trically. Results showed that intragastric administration of tetrahydroxy-stilbene glucoside improved the learning and memory abilities of the transgenic mice through increasing NR2B receptors and Fyn expression. It also reversed parameters for synaptic interface structure of gray type I. These findings indicate that tetrahydroxy stilbene glucoside has protective effects on the brain, and has prospects for its clinical application to improve the learning and memory abilities and treat Alzheimer＇s disease.

Tetrahydroxy stilbene glucoside reduces the cognitive impairment and overexpression of amyloid precursor protein induced by aluminum exposure

Objective Excessive aluminum （Al） exposure impairs neurocognitive function in humans and animals. Epidemiologic studies have shown a potential linkage between chronic Al exposure and Alzheimer’s disease. The present study aims to evaluate the effects of tetrahydroxy stilbene glucoside （TSG）, the extract from herbal medicine Polygoni Multiflori, on cognitive impairment and the over-expression of hippocampal amyloid precursor protein （APP） induced by chronic exposure to Al in rats. Methods Rats were treated with 0.3% aluminum chloride （AlCl3） prepared in the drinking water for 90 d. AlCl3-treated animals were then randomly assigned to receive vehicle, TSG （4 g/kg）, or Vitamin E （VE; 40 mg/kg） treatment for 5 months. VE served as a positive control. The effect of TSG was evaluated by passive avoidance task, and APP expression was evaluated by Western blotting. Results Following exposure to AlCl3 for 90 d, animals displayed a striking decrease （〉80%） in step-through latency in the passive avoidance task and a significant increase in the expression of APP in the hippocampus. Both TSG and VE significantly ameliorated the performance impairment in the passive avoidance task, and suppressed the over-expression of APP. Moreover, the effects of TSG, but not of VE, were in a time-dependent manner. Conclusion TSG may possess therapeutic effects against Alzheimer’s disease.

Tetrahydroxy stilbene glucoside improved the behavioral disorders of APP695V717l transgenic mice by inhibiting the expression of Beclin-1 and LC3-Ⅱ

OBJECTIVE:To observe the effect of tetrahydroxy stilbene glucoside(TSG) on the behavior of APP695V717 I transgenic mouse models and the expression of autophagy-associated proteins Beclin-1and LC3-Ⅱ.METHODS:Forty 3-month-old APP695V717 I transgenic mice were randomized equally into either a TSG group(n = 20) or a model group(n = 20).A normal control group consisted of C57BL/6J mice of the same age and background(n = 20).The TSG group received TSG intragastric administration for1 month.Behavior was measured using the Morris water maze and the Y-maze tests.Changes in protein expression and mRNA of autophagy-associated Beclin-1 and LC3-Ⅱ in mice hippocampus were detected by western blot and Reverse Transcription-Polymerase Chain Reaction(RT-PCR) analyses.RESULTS:The number of electric-stimulus escapes significantly increased and the Morris water maze test showed prolonged escape latency,greater swimming distance,less time taken to cross the exact former platform location in the model group,and increased mRNA and protein expressions of Beclin-1 and LC3-Ⅱ compared with the control group(P < 0.05).The TSG group showed a decrease in the number of electric-stimulus escapes,shorter escape latency and swimming distance,greater time taken to cross the exact former platform location,and decreased mRNA and protein expressions of Beclin-1 and LC3-Ⅱ compared with the model group(P< 0.05).CONCLUSION:These results indicate that tetrahydroxy stilbene glucoside can decrease expressions of Beclin-1 and LC3-Ⅱ in the autophagy pathway.It can attenuate injury to endoplasmic reticulum functions caused by Ab neurotoxicity,improving learning,memorizing,and spatial orientation behavior in mice.