The Effect And Mechanism Of Bushen Yizhi Formula Via PI3K/Akt/GSK3? Signaling Pathway In Mice With Mild Cognitive Impairment Based On Network Pharmacology

Objective:To explore the potential targets and pathways of Bushen Yizhi Formula in intervening MCI,by using the network pharmacology analysis method.To verify the effects and mechanism of Bushen Yizhi Formula in intervening MCI via animal experiments.Methods:(1)Network pharmacology:Screening the active ingredients and targets of Bushen Yizhi Formula through the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).TCMSP and TTD database were used to screen AD related therapeutic targets.Constructing the formula-AD target network,and forecast the potential targets for Alzheimer's disease.Then constructing the interaction network of target proteins,analyzing the topological structure.GO analysis and KEGG analysis of screened core targets between drug target and disease target was carried out by using David 6.8 database.(2)Animal experiment:The 12-week-old APP/PS1 mice were used as the model,and the C57BL/6J wild-type mice of the same age as the control.Amyloid deposition was observed by Congo red staining.Silver nitrate staining was used to observe the tangles of nerve fibers.ACHE and ChAT kit to detect the vitality of ACHE and ChAT.The levels of A?42 and P-Tau were detected by Elisa.Immunohistochemistry was used to detect the expression of P-Tau in the hippocampus.The expression of proteins related to PI3K/Akt/GSK3? signaling pathway detected by Western Blot.Results:(1)101 active components and 40 potential targets were screened out.A total of 38 terms were obtained by GO enrichment analysis,including 6 molecular function,21 biological process,and 11 cell composition,11 potential signaling pathways were obtained by KEGG enrichment analysis,mainly involving synaptic function and protein phosphorylation pathway of Tau.(2)Animal experiments showed that Bushen Yizhi formula could improve the spatial learning and memory ability of MCI mice,reduce senile plaque deposition and nerve fiber tangles in the hippocampus of mice,increase the content of acetylcholine,and reduce the content of A?42 and P-tau in peripheral blood.At the same time,Bushen Yizhi formula can work through PI3K/Akt/GSK3? signaling pathway,by increasing the phosphorylation of PI3K and Akt,reducing the phosphorylation of GSK3? proteins,thus inhibiting the phosphorylation of Tau protein.Conclusions:Bushen Yizhi Formula can improve MCI related indicators,and reduce phosphorylation of Tau through PI3K/Akt/GSK3? signaling pathway,thus improving the learning and memory function.