Wuzang Wenyang Huayu Tang Treatment of vascular dementia by modulation of BCL-2/BAX/Caspase3: An integrated in vitro cellular assay and network pharmacological analysis

• WWHT exemplifies the strengths of TCM in treating VD through the concepts of “ the brain governs the spirit” and “the five organs store the spirit.”. • Wuzang Wenyang Huayu Tang can protect HT22 cells by regulating apoptosis-related protein. • Multi-target, multi-component and multi-pathway advantages of Wuzang Wenyang Huayu Tang for vascular dementia highlighted through network pharmacology and molecular docking. This project explores Wuzang Wenyang Huayu Tang (WWHT) 's potential mechanisms for treating vascular dementia (VD) based on network pharmacology and experimental validation. TCMSP was used to screen the active ingredients and targets of WWHT; GeneCards was used to identify VD-related targets; Cytoscape 3.10.0 was used to generate an "active ingredient-target" network map; STRING and Cytoscape were used to generate a PPI network map; Metascape and WeiShengxin performed GO and KEGG analysis to screen potential signaling pathways and explore the mechanisms; cell experiments were performed to verify the relevant targets. 117 active components of WWHT were screened, and 146 gene targets intersected with VD. The high-frequency nodes in the PPI network include CASP3, MMP9, BCL2, etc. GO analysis showed that the biological functions involved hormones, nitrogen compounds, and other responses; KEGG analysis revealed that the pathways were concentrated in the signaling pathways such as AGE-RAGE, MAPK, etc. To treat VD, WWHT may enhance HT22 morphology in ischemia-hypoxia, control apoptosis-related proteins, and promote HT22 proliferation. As a means to effectively treat VD, WWHT may protect neuronal cells, regulate cell apoptosis, and reduce brain damage by using a multi-component, multi-target, and multi-pathway strategy.