Screening of herbs for vascular dementia: Through the combination of reverse network pharmacology and traditional Chinese medicine enrichment analysis.

Background: Vascular dementia (VaD) represents the second most prevalent form of cognitive impairment following Alzheimer's disease. Its pathological mechanisms encompass a complex interplay of cerebral ischemia, inflammatory responses, oxidative stress, and neuronal apoptosis. Current clinical interventions predominantly target cerebral circulation enhancement and neuroprotection; however, these approaches exhibit limitations in efficacy, single-target specificity, and significant adverse effects. Traditional Chinese medicine (TCM) offers a novel therapeutic paradigm for complex diseases owing to its multi-target synergistic effects, low toxicity profile, and integrated preventive and therapeutic benefits. Objective: This study aims to identify the potentially effective active components in TCM targeting VaD, and to elucidate the multi-target regulatory mechanisms. Methods: This study employed a "disease-gene-drug" reverse screening model, integrating bioinformatics and network pharmacology, to systematically identify potential TCM candidates for VaD treatment and elucidate their multi-target regulatory mechanisms. Results: A total of eight TCM agents with potential VaD therapeutic efficacy (including Niuxi, Pueraria lobata, and Citrus aurantium) were identified, alongside nine active compounds and nine therapeutic targets. Notably, Gehua and Zhike were reported for the first time to exhibit potential VaD therapeutic effects. Furthermore, molecular docking technology was utilized to investigate the binding affinity and interaction modes of these nine active compounds with key targets. Conclusions: To our knowledge, this study is among the first to apply reverse network pharmacology combined with TCM enrichment specifically to VaD.