Eriodictyol Ameliorates Alzheimer's Disease Cognitive Function By Promoting The Proliferation Of Microglia

Objective:The subject used the 5xFAD mouse model of Alzheimer's disease(Alzheimer's disease,AD),which gave intervention to Eriodictyol.The behavioral manifestations of the animals after oral administration,changes in A? plaques and changes in microglial cells are observed,and the cells and molecular mechanisms of microglial cells to M1-type activation are promoted.The role of Eriodictyol treatment for the 5xFAD mouse model of Alzheimer's disease and its possible mechanisms are clarified.It provides a scientific theoretical basis for the future application of Eriodictyol to treat AD.Method:This study conducted ATP experiments to detect energy metabolism of microglial cells and used fluorescent quantitative PCR testing to detect the level of inflammation in cells after treating the primary microglial cells with different concentrations of Eriodictyol.This experiment used 26-week-old 5xFAD female mice to establish a model of cognitive dysfunction in Alzheimer's disease.The mice were divided into wild group,AD group,and AD drug group,each group of 7-10 mice.The method of administration was drug gastric irrigation,and each group of mice were administrated every other day,three times a week,lasting 8 weeks.The AD drug group with 4 mg/kg of Eriodictyol as the final concentration of the drug,and the drug-assisted solvent(200?l DMSO plus 5 ml polyglycol plus 45 ml physiological saline)was given to the stomach at 10?l /g per mouse,while the wild group and the AD group were given the equivalent amount of drug-assisted solvent to the stomach.Behavioral tests were carried out during administration and the weight of mice before and after administration was recorded.The mice were executed at the age of 8 months,taking the mouse brain tissue to respectively extract proteins and make slices.Western blot method detected the level of the mouse brain tissue amyloid-? protein(A?)and the surface marker of microglial cells Iba1,the immunofluorescent tissue chemical staining method detected the expression and distribution of amyloid-?(A?)and Iba1 in the mouse brain tissue,and the statistical analysis of GraphPad Prism 7.0 statistical software was applied to each group of experimental data.Results:1.After the primary microglial cells were treated with different concentrations of drugs,the cell metabolism capacity increased significantly,with the most significant increase in the amount of 10?M(P<0.001);2.After LPS stimulation 0 h,24 h,the primary microglial cells treated with LPS stimulation were detected with fluorescent quantitative PCR and mRNA levels of anti-inflammatory factors such as IL-4 and IL-10,and the results showed that the expression level of iNOS(P<0.01)was significantly inhibited,at the same time the expression level of IL-10 was notably increased;3.The weight measurement results showed no significant difference in weight in mice at the beginning of animal modeling and after administration(N.S.);4.In the new object recognition test,mice in the wild group and AD drug group had a clear preference for new objects(P<0.05),while mice in the AD group had no clear preference for new objects(N.S.);5.During the water maze study period,the wild group and the AD drug group consumed significantly less time to reach the platform(P<0.01)than the AD group,and they crossed the platform more frequently during the study;6.The number of microglial cells in the hippocampus in the AD drug group increased significantly compared with the wild group and the AD group,and the proliferation of microglial cells was more obvious(P<0.05).Among them,there was a significant decrease in inert plaques in A? plaques(P<0.01)and a significant increase in the number of microglial cells around the plaque after administration(P<0.05)compared to the AD group.Conclusion:Experiments have shown that Eriodictyol can significantly improve learning cognitive ability of 5xFAD mice.In addition,Eriodictyol can increase the proliferation and migration energy of microglial cells,making amyloid-? precipitation(amyloid-beta,A?)denser,thereby reducing neurotoxicity of A?.These results suggest that Eriodictyol may be a potential drug for AD.