Objective:To observe the effect of the total alkaloids of Dendrobium nobile Lindl on the leing and memory impairment of APP/PS1 transgenic mice. Methods:Seven months male APP/PS1 transgenic mice(n=24)were randomly divided into two groups:APP/PS1+vehicle and APP/PS1+DNLA(the total alkaloids of Dendrobium nobile Lindl)groups. Age-matched male wild-type(WT) littermates(n=24)were randomly divided into two groups:WT+vehicle and WT+DNLA groups. The normal group and APP / PS1 group were garaged with normal volume of saline(NS)for 6 consecutive months. The mice in the normal administration group and APP/PS1-administered group were given the daily total alkaloid of Dendrobiumnobile 40 mg·kg-1. Morris water maze was used to detect leing and memory ability in mice. At the end of the behavioral test,the cortical area of senile plaques were detected in the mice by anesthesia,and the survival of the hippocampal neurons was detected by Nissls staining.Transmission electron microscope was performed to observe neuron structure and synaptic structure in hippocampus. The levels of IL-1βwere measured by ELISA .The levels of Aβ1-40,Aβ1-42 and the expression of GFAP,IL-6,COX-2,p-NF-ΚB,p-p38,PSD95 and SYP in hippocampus were detected by West blot. Results:Compared with WT+vehicle group,the mean escape latency was markedly increased and the time percentage in target quadrant showed notable decrease in APP/PS1+vehicle group. The number of neurons were significantly reduced in hippocampal CA1 region. The results of transmission electron microscope showed that the structure of neuron and synaptic structure were damaged and the number of synaptic density was decreased. The amyloid plaques,Aβ1-40,Aβ1-42 contents the protein expression of GFAP,IL-6,COX-2,p-NF-κB and p-p38 were increased, meanwhile,the protein expression of PSD95 and SYP were dramatically decreased in the hippocampus in APP/PS1+vehicle group. These effects in WT+DNLA group showed no notable differences compared to the WT+vehicle group. However,compared with APP/PS1+vehicle group,the mean escape latency was decreased and the time percentage in target quadrant was notably increased in APP/PS1+DNLA. Moreover,the number of neurons were significantly increased in hippocampal CA1 region. The structure of neuron and synaptic structure was improvement Furthermore,the amyloid plaques,Aβ1-40, Aβ1-42 contents,GFAP,IL-6,COX-2,p- NF-κB and p-p38 expression were decreased in the hippocampus,the protein expression of PSD95 and SYP were significantly increased in APP/PS1+DNLA group. Conclusions:Under the experimental conditions,DNLA attenuates the leing and memory loss of Alzheimers disease mice and reduces the number of senile plaques and increases the number of surviving neurons. The mechanism may be related to level of Aβ,activation of astrocytes, activation of astrocytes,inhibition of NF-κB and p38 and improvement of synaptic dysfunction.