Work

Dihydromyricetin ameliorates vascular dementia by promoting angiogenesis via the VEGFR2 pathway: Network pharmacology, molecular docking and experimental validation

Year: 2025

Type: article

Abstract: BACKGROUND: To date, few therapies have proven effective in improving cognitive function in vascular dementia (VD), underscoring the need for new treatment strategies. Dihydromyricetin (DMY), a natural flavonoid with neuroprotective properties, has not been explored for VD treatment. PURPOSE: This study aimed to evaluate the therapeutic efficacy of DMY in VD and elucidate its underlying mechanisms. METHODS: Network pharmacology approaches were used to predict and screen the key targets of DMY in VD, and validated by molecular docking, molecular dynamics simulation and surface plasmon resonance (SPR). Experimental models included bilateral common carotid artery stenosis (BCAS) mice and bEnd.3 cells under hypoxic/hypoglycemic conditions. Vascular endothelial growth factor receptor 2 (VEGFR2) inhibition was used to further assess mechanistic specificity. RESULTS: The network pharmacological analysis predicted that DMY acts via the VEGFR2 pathway to promote angiogenesis. Molecular docking, molecular dynamics simulation and SPR confirmed strong binding affinity and stability for DMY and 3 key targets (VEGFR2, SRC, and MAPK14). In vivo, DMY improved cognitive performance, increased cerebral blood flow (CBF), reduced hippocampal damage, and upregulated angiogenesis markers and key targets at protein/mRNA levels. In vitro studies further confirmed therapeutic effects of DMY, which were reversed by VEGFR2 inhibition. These effects were reversed by VEGFR2 inhibition, confirming the involvement of VEGFR2 pathway. CONCLUSION: To our knowledge, this is the first study to demonstrate that DMY improves cognitive function in VD by enhancing angiogenesis and CBF through VEGFR2 pathway activation. Our findings offer new insights into the therapeutic potential of DMY for VD.

Source: Phytomedicine

DOI: 10.1016/j.phymed.2025.157593