It is believed that neuronal death caused by abnormal deposition of amyloid-beta (Aβ) peptide is the major cause for the cognitive decline in Alzheimers disease (AD).Adult neurogenesis plays a key role in rescue of impaired neurons and amelioration of cognitive impairment.In the present study, we demonstrated that osthole, a natural coumarin derivative, was capable of promoting neuronal stem cells (NSCs) survival and inducing the cells proliferation in vitro.In osthole-treated APP/PS1 transgenic mice, a significant improvement in learning and memory function was determined, which associated a significant increase in the number of newborn neurons (Ki67+/NF-M+) and decrease in apoptotic cells in hippocampal region of the brain.The observations suggested that osthole promoted NSCs proliferation and supported neurogenesis,thus efficiently rescued impaired neurons in the hippocampus and ameliorated the cognitive impairment.We also found that osthole treatment activated Notch pathway and up-regulated the expression of selfrenewal genes Notch 1 and Hes 1 mRNA in the NSCs;However, when Notch activity was blocked by γ -secretase inhibitor DAPT, the augmentation of Notch 1 and Hes 1 protein was relieved, and the proliferation-inducing effect of osthole was abolished, implicating the effects of osthole is at least in part mediated by activation of Notch pathway.