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Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription, could alleviate cognitive dysfunction of Alzheimer's disease (AD) patients.However, the detail mechanisms remain elusive.In the present study, the effects of Danggui-Shaoyao-san (DSS) on Aβ-induced cholinergic neuron injury were examined to elucidate the possible mechanism.The results showed that treatment with DSS containing serum attenuates Aβ-induced apoptotic cell death in primary cultured cholinergic neuron.DSS exerted significant protective effects on cholinergic neuronapotosis by ameliorating the decrease in Bcl-2 and the increase in cleaved caspase-3 induced by Aβ 25-35.In addition, phosphorylated cyclic AMP response element-binding protein (pCREB) was impaired in Aβ 25-35-treated cholinergic neurons, and DSS enhanced the activation of CREB.Collectively, these findings indicate that DSS ameliorates Aβ-induced cholinergic neuronapotosis via the CREB/Bcl-2 signaling pathway.Thus, it suggests that DSS can be used as a potential therapeutic agent in the long-term treatment of Alzheimer's disease and senile dementia.