Investigating the Pharmacological Basis of Xiaochaihu-Tang in Diabetic Cognitive Impairment: A Network Pharmacology Approach

Background/Objectives: Diabetic Cognitive Impairment (DCI) involves cognitive impairment resulting from diabetes-triggered metabolic abnormalities and neuroinflammation; however, the therapeutic mechanisms of Xiaochaihu-tang (XCHT) remain unclear. Methods: This study systematically explored the potential pharmacological mechanisms of XCHT on DCI using network pharmacology and molecular docking analysis. Results: Based on 263 bioactive compounds from XCHT, 1017 intersecting genes with DCI were identified. Protein–protein interaction, GO, and KEGG analyses narrowed these to 22 major target genes involved in inflammation, apoptosis, and metabolic pathways. Validation using public transcriptomic datasets (GSE161355, GSE122063, GSE5281) and ROC–AUC analysis identified TLR4, BCL2, and STAT3 as top candidate targets. Furthermore, molecular docking analysis showed a notably stable binding interaction for TLR4–Stigmasterol, suggesting a possible structural basis by which XCHT may modulate TLR4 signaling in DCI. Conclusions: These findings suggest that XCHT may multi-dimensionally regulate DCI, providing essential foundational data for future cellular and animal experimental validation.