Integrating network pharmacology and experimental validation deciphers the improving effect and mechanisms of Shenwu Yizhi capsule on cognitive impairment in vascular dementia rats.

The therapeutic mechanisms of Shenwu Yizhi Capsule (SWYZC), a widely used treatment for vascular dementia (VD), remain unclear. This study integrated network pharmacology and experimental methods to elucidate the effects and mechanisms of SWYZC on cognitive function in VD rats. A VD model was established via bilateral common carotid artery occlusion (2-VO). Cognitive function was evaluated using the Morris water maze (MWM), and hippocampal neuronal morphology was assessed via hematoxylin-eosin (HE) staining. Active compounds and targets of SWYZC were identified using the TCMSP, PubChem, and Swiss Target Prediction databases, while VD-related targets were retrieved from OMIM, TTD, and GeneCards. Venny 2.1.0 identified overlapping targets between SWYZC and VD. The STRING database analyzed protein-protein interaction (PPI) networks, and the DAVID database conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Apoptosis and dendritic function were evaluated to explore therapeutic mechanisms. Molecular docking was performed using AutoDock Vina. SWYZC significantly ameliorated cognitive deficits and hippocampal neuronal damage. PPI network analysis identified 20 key targets between SWYZC and VD, including TP53, SRC, CASP3, etc. GO and KEGG analyses indicated that apoptosis, inflammation, and synaptic injury targets were central to SWYZC's therapeutic effects on VD. Moreover, experimental validation demonstrated that SWYZC significantly upregulated PSD95 and PGC-1α expression while downregulated Cleaved Caspase-3, Bax, and connexin43 (CX43) levels. Molecular docking indicated that celabenzine exhibited strong binding to Bax and CX43. Collectively, SWYZC improves memory function and mitigates hippocampal neuronal damage in VD rats by inhibiting apoptosis and promoting synapse formation.