Exploring the mechanism of Yizhi Tongmai decoction in the treatment of vascular dementia through network pharmacology and molecular docking

BACKGROUND: Vascular dementia (VaD) is a degenerative cerebrovascular disease that leads to progressive decline of patients’ cognitive ability and memory. Yizhi Tongmai (YZTM) decoction is an empirical prescription first formulated by Professor Guomin Si. Our previous experiments proved the effectiveness of this prescription in the treatment of VaD. In this study, we aimed to use network pharmacology and molecular docking technology to systematically explain the potential anti-VaD mechanism of YZTM. METHODS: We identified the core compounds of YZTM and their potential targets through the TCMSP, BATMAN, and SwissTargetPrediction databases. Then, we identified the molecular targets of YZTM in VaD using the Online Mendelian Inheritance in Man and GeneCards databases. The common targets of YZTM and VaD were screened out, and then the pathways of these target genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery v6.8. Molecular docking was used to verify the relationship between the core compounds and proteins. RESULTS: Through network pharmacology analysis, we discovered that the 5 core compounds in YZTM exert an anti-VaD effect. The potential mechanism of YZTM anti-VaD may be through inhibiting the NLRP3 inflammasome, TNF signaling pathway, and toll-like receptor signaling pathways. Subsequently, key compounds were docked with related proteins in the NLRP3 inflammasome (NLRP3, ASC, caspase-1, interleukin-18, and interleukin-1 β) using molecular docking technology. The compounds were found to spontaneously bind to the proteins. CONCLUSIONS: YZTM may exert an anti-VaD effect through inhibition of the NLRP3 inflammasome. In addition, TNF signaling pathway and toll-like receptor signaling pathway may also be its underlying mechanism. The application of network pharmacology and molecular docking technology may provide a novel method for research of Chinese herbal medicine. YZTM may also provide a complementary treatment option for patients with VaD