Objective: To investigate the protection effect and mechanism of Shengjiangsan on learning and memory abilities of vascular dementia (VD) rats. Method: SD rats were randomly divided into normal group

sham-operation group

model group

positive drug group (donepezil hydrochloride

1 mg·kg-1)

Shengjiangsan low

middle and high dose groups (0.67

1.33

2.66 g·kg-1). VD models were reproduced by improved two vessel occlusion method (2VO)

and the intragastric administration of the drugs was started 1 week after surgery

for 8 consecutive 8 weeks. The effect of Shengjiangsan on learning and memory abilities of VD rats

as well as the orientation navigation and space exploration behaviors were observed by using 2VO method. HE staining was used to investigate the pathomorphology in hippocampus; Western blot and immunofluorescence assays were used to explore the expression levels of VEGF

Nestin

and key proteins (p-LRP

p-GSK3β

LRP

GSK3β and β-catenin) in hippocampus. Result: As compared with the model group

all doses of Shengjiangsan could prolong the latency of VD rats in passive avoidance test

shorten the latency of the orientation navigation and space exploration in Morris water maze test and promote the repair of pathological injury in some degree in a dose-dependent manner. In addition

Shengjiangsan up-regulated the protein expression levels of VEGF

Nestin

p-LRP

p-GSK3β and β-catenin in hippocampus in a dose-dependent manner (P<0.05

P<0.01). Conclusion: Shengjiangsan could improve the behaviors of VD rats in learning and memory as well as spatial recognition by activating Wnt signal pathway.