Byakangelicin attenuates vascular dementia by modulating the KDR–NOS3 axis: An integration of network pharmacology and experimental validation

Vascular dementia (VaD) is a major cause of cognitive impairment with limited treatment options. Byakangelicin (Byn), a natural coumarin compound, has shown potential neuroprotective effects, but its mechanism in VaD remains unclear. This study employed an integrated approach combining network pharmacology, molecular docking, and experimental validation to investigate Byn‘s therapeutic action. Network analysis prioritized KDR and NOS3 as core targets, which was corroborated by molecular docking. In a 2-VO–induced VaD rat model, Byn administration dose-dependently improved cognitive function, alleviated hippocampal damage, and reduced neuroinflammation. Mechanistically, Byn upregulated the KDR-NOS3 axis, enhanced Akt/eNOS phosphorylation, and suppressed apoptotic signaling. Critically, the protective effects of Byn were abolished by co-administration of KDR or NOS3 inhibitors. Our findings reveal that byakangelicin attenuates VaD by modulating the KDR–NOS3 signaling pathway, offering a promising therapeutic strategy and a solid mechanistic basis for further drug development. • Byakangelicin significantly improves cognitive impairment and reduces hippocampal neuronal damage in a rat model of vascular dementia. • Network pharmacology and molecular docking identify KDR and NOS3 as core targets of Byn, linked to angiogenesis and vascular regulation. • This study provides preliminary experimental evidence that Byn may ameliorate VaD by modulating the KDR–NOS3 pathway, laying a foundation for further research.