A Computational Systems Pharmacology Strategy to Decode Biomarker Networks and Therapeutic Mechanisms of Wenshen Yang Formula in Vascular Cognitive Impairment

Objective To integrate computational pharmacology with multiomics principles in order to decode the systematic mechanisms and potential biomarker network of Wenshen Yang Formula (WSYF) for treating vascular cognitive impairment (VCI), providing a data‐driven rationale for its clinical application and future biomarker‐guided studies. Methods We employed a computational systems pharmacology approach. Active constituents of WSYF were sourced from the TCMSP and TCMID databases, representing a phytochemical “omics” profile. VCI‐related targets were curated from the GeneCards database. Shared targets were subjected to protein–protein interaction (PPI) network construction, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment to delineate the formula’s multitarget, multipathway signature. Molecular docking validated key compound–target interactions, serving as a computational proxy for biomarker–target engagement. Results The analysis identified 20 active ingredients targeting 406 proteins, with 261 overlapping targets shared with VCI pathogenesis. Core targets, including SRC, HSP90AA1, MAPK3, MAPK1, and PIK3CA, were identified as central nodes in the therapeutic network. Pathway analysis revealed significant enrichment in PI3 K‐Akt, cAMP, and MAPK signaling cascades—critical pathways for neuroprotection, synaptic plasticity, and inflammation. Molecular docking confirmed strong binding affinities, most notably between phytosterols (e.g., CID 5280794) and key targets HSP90AA1 and MAPK1. This target–pathway map proposes a multicomponent biomarker network through which WSYF may modulate P‐tau pathology, neuronal apoptosis, and synaptic function in VCI. Conclusion This study translates traditional herbal formula analysis into a systems‐level, biomarker‐informed framework. We propose that WSYF acts via a coordinated network targeting HSP90AA1, MAPK, and PI3K/Akt pathways, with phytosterols as pivotal bioactive constituents. The identified target and pathway signature provides a testable biomarker hypothesis for future clinical validation. This approach bridges traditional medicine and modern precision neurology, offering a roadmap for developing mechanism‐based biomarkers to stratify VCI patients and objectively monitor treatment response to complex herbal interventions.