Objective To investigate the potential mechanism of Sijunzi Decoction in treating Alzheimer's disease(AD)by network pharmacology and experiments.Methods The effective components and related targets of Sijunzi Decoction were re-trieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),while DisGeNET and GeneCards Databases were used to collect AD targets.The common target protein-protein interaction(PPI)network was es-tablished by String database,and the'drug-active ingredient-target-disease'network was drawn by Cytoscape software.Gene On-tology(GO)term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of key tar-gets was performed using Database for Annotation,Visualization and Integrated Discovery(DAVID).Twenty-four 3-month-old SPF APP/PS1 double transgenic male mice were randomly divided into the model group,the low-dose and high-dose experimental groups,and 8 C57BL6 mice were used as the negative control group.Low and high dose experimental groups were fed for four months.Morris water maze test was used to detect the memory ability and space exploration ability of mice,and the oxidative stress indexes such as superoxide dismutase(SOD),acetylcholinesterase(AChE)and malonaldehyde(MDA)were detected by relevant kits.The pathological changes of brain were detected by electron microscopy.Results Finally,128 active components of Sijunzi Decoction were screened out,and 49 common targets with AD were obtained.Among them,AKT1,Caspase-3(Casp3)and TNF were the core targets,which were closely related to PI3K-Akt signaling pathway.Animal experiments confirmed that an-imal experiments could improve the cognitive function of mice,pathological results showed that Sijunzi decoction could alleviate the mitochondrial damage,and biochemical indicators showed that Sijunzi decoction could increase the AChE level in the brain of mice and reduce the SOD and MDA levels.Conclusion Sijunzi Decoction can alleviate the cognitive function changes,brain pathological changes and biochemical changes induced by APP/PS1 in mice,and provide a basis for further explanation of its ma-terial basis and mechanism.