Abstract: Objective：To examine the protective effect and the potential mechanism of osthole（Ost） on the behavioral disorders in presenile and vascular dementia model mice. Methods：Icv injection of β-amyloid peptide (Aβ_25-35 ) 3 μL (1.0 mmol·L^-1, icv) was used as a presenile dementia animal model. Temporary making obstructing-reperfusion bilateral common carotid arteries obstruction was used as a repeated cerebral ischemia-reperfusion model.  Mice were treated with osthole (15,7.5 mg·kg^-1, ip) for 10 days and the spatial learning and memory as long as the spatial exploration abilities were assessed via Morris water maze test and exploratory movement test, respectively. The levels of Nitric oxide (NO) and Nitric oxide synthase (NOS) were also measured. Results：Osthole significantly improved the behavioral deficits in both dementia models (P<0.01 or P<0.05). Osthole (15,7.5 mg·kg^-1) also decreased the level of NO and NOS in the mice brain (P<0.01). Conclusion：Osthole can improve the spatial learning and memory and spatial exploration abilities in two mice models of dementia,  which is related to decreasing NO and NOS levels.

Key words: osthole, &, beta, -amyloid protein, cerebral ischemia-reperfusion, learning and memory, NO, NOS