Protective effect of Shouwu Yizhi decoction against vascular dementia by promoting angiogenesis

Shouwu is a traditional Chinese medicine(TCM)with neuroprotective effect.Shouwu Yizhi decoction(SYD)was designed based on TCM theory.However,little is known about the roles of SYD in Vascular dementia(Va D).The present study aimed to evaluate the potential effects of SYD on the vascular cognitive impairment and explore the underlying mechanism by establishing focal cerebral ischemia/reperfusion(I/R)rat model to induce Va D.SYD administration(54 mg·kg^(-1))for 40 days obviously improved the vascular cognitive impairment in the middle cerebral artery occlusion(MCAO)rats as evidenced by the declined neurological deficit score and shortened escape latency via neurological deficit assessment and Morris water maze test.Moreover,SYD decreased neuron damage-induced cell death and ameliorated the ultrastructure of endothelial cells in the MCAO rats,thereby alleviating Va D.Mechanistically,SYD caused increases in the expression of vascular endothelial growth factor(VEGF),CD34 and CD31,compared with the MCAO rats in coronal hippocampus.Simultaneously,the expression level of mi R-210 was elevated significantly after SYD administration,compared with the vehicle rats(P<0.01).The expression of Notch 4 at both m RNA and protein levels was upregulated remarkably along with the notably downregulated DLL4 expression under SYD administration compared with the vehicle rats(P<0.05).Overall,the above results indicated that SYD promoted angiogenesis by upregulating VEGF-induced mi R210 expression to activate Notch pathway,and further alleviated neuron damage and ameliorated the ultrastructure of endothelial cells in the MCAO rats,ultimately enhancing the cognition and memory of MCAO rats.Therefore,our findings preliminarily identified the effect and the mechanism of action for SYD on Va D in rats.SYD could be a potential candidate in treatment of Va D.