Effect And Mechanism Of α-mangostin Derivative On Alzheimer’s Disease Model Rats

Background:Alzheimer’s disease（AD）is a progressive and irreversible neurodegenerative degenerative diseases.AD has high incidence,low treatment,and it’s social burden is heavy,which makes the whole world pay much attention to it.Anti-Alzheimer’s research has become an important topic in the field of geriatrics.AD-related drugs continue to develop,but still mainly remain at the level of symptomatic treatment,can not completely prevent the neuronal degeneration of the mechanism of research and development.α-Mangostin is a kind of ketone compounds separated from mangosteen peel,which has a wide range of biological and pharmacological activity.It is a small molecular mass of lipid-soluble molecules was confirmed by previous studies that it could penetrate the blood-brain barrier and the derivatives could significantly improve the cell damage caused by H₂O₂ in PC12 cells.So it is one of the potential candidate compound for the treatment of AD.Objective:In this subject we established the senile dementia rat models induced by bilateral hippocampal injection of Aβ_25-355-35 to investigate the effects of the new compound?-mangostin derivative on AD and to explore it’s possible mechanism,provide new ideas and experimental basis for the compound treatment of AD.Methods:（1）The senile dementia rat models induced by bilateral hippocampal injection of Aβ_25-355-35 will be divided into six groups,they are model group（physiologic saline）;high doses group（20mg/kg MG1）;middle doses group（10mg/kg MG1）;lowdoses group（5mg/kg MG1）;positive group（1mg/kg Donepezil HCl）and sham group（physiologic saline）.All the groups had 8 rats.The behavioristics of every group were tested by using Morris Water Maze and Open field test.（2）HE straining Nissl straining and Silver staining were used to observe the change of brain in the rats,then immunohistochemistry was used to evaluate the expression of Aβ_1-42-42 in the rat hippocampus and cortex of every groups,furthermore Western Blot was used to assay for the expression of Phospho-Tau（PHF13）in the rat brain.Results:（1）Compared with the control group,the spatial learning,memory abilities and exploratory behavior of model group were significantly reduced.However,compared with the model group,the behavioristics of rats administrated with MG1 were significantly improved（P<0.05）.（2）For Model group,a large number of neurons were degeneration and lost,there can observe NFT and SP in hippocampus and cortex,the expression of PHF13 up-regulation.On the other hand the neurons in hippocampuswereincreased,NFTwereweaken,andthe immunohistochemistry was demonstrated that the expression of Aβ_1-42was decreased in hippocampus,in addition the expression of PHF13down-regulated after drugs administration.Conclution:（1）?-mangostin derivative can effectively improve AD rat behavior disorders.（2）?-mangostin derivative can effectively reduce the loss of neurons in hippocampus area,weakening P-Tau and NFT,eliminate SP.