To explore the mechanism of action of Huangqi Jianzhong Decoction in treating gastric ulcer(GU) through bioinformatics analysis and further validation with animal experiments.Methods:Active components and targets of Huangqi Jianzhong Decoction were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Swiss Target Prediction database.GU-related targets were extracted from gene(GeneCards) and drug(Drug Bank) databases.Using Cytoscape 3.7.2 software,the “active component-potential therapeutic target” network for Huangqi Jianzhong Decoction in treating GU was constructed.STRING and DAVID databases were used to obtain the protein-protein interaction(PPI) network,Gene Ontology(GO) enrichment,and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis.The potential mechanisms of Huangqi Jianzhong Decoction in preventing and treating GU were further verified through molecular docking and animal experiments.Results:Huangqi Jianzhong Decoction has 131 potential targets for the treatment of GU,with core targets including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA) and protein kinase B1(AKT1).KEGG analysis indicated that pathways such as the phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signaling pathway play important roles.Molecular docking suggested good binding affinity between core targets and core components.Animal experiments showed that compared with the normal group,the model group had increased ulcer index and inflammatory infiltration in gastric tissues,with significantly elevated expression of interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α)(P<0.01),and significantly decreased expression of PI3K and phosphorylated protein kinase B(p-AKT)(P<0.01).Compared with the model group,the treatment group showed significantly reduced gastric injury,downregulated expression of IL-6,IL-1β,and TNF-α(P<0.01),and upregulated expression of PI3K and p-AKT(P<0.01).Conclusion:Huangqi Jianzhong Decoction exhibits multi-pathway and multi-target characteristics in its intervention effects on GU and the mechanism may be achieved through accelerating gastric mucosal repair and reducing gastric injury by activating the PI3K/AKT signaling pathway and lowering inflammation.