Objective To observe the effect of Yishen Huazhuo Prescription on learning and memory ability and hippocampal synapses key protein CREB of senescence-accelerated prone mouse（ SAMP8） model. Methods Totally 30 SAMP8 mice of 12 months were randomized into SAMP8 group

donepezil group and Yishen Huazhuo Prescription group. Another 10 senescence-resistant（ SAMR1） mice were selected as the control group. The SAMP8 group and the control group were not intervened

Yishen Huazhuo Prescription group was given Yishen Huazhuo Decoction（ 9.62mg/kg）

and donepezil group was treated with donepezil（ 0.01mg/g）. The learning and memory ability was detected with Morris water maze task. The microcosmic morphology of hippocampal neuron synapses of mice in each group was observed under electron microscope. The CREB protein expression in the hippocampus was detected with Western blot method. Results In place navigation test

the latent time and total swimming distance of mice in the SAMP8 group were significantly prolonged as compared with the SAMR1 group（ P < 0. 05）. The latent time and total swimming distance of mice in Yishen Huazhuo Prescription group were apparently shortened as compared with the SAMP8 group（ P < 0. 05）. In spatial probe test

the number of mice through target quadrant and t /t in the SAMP8 group were significantly reduced as compared with the SAMR1 group（ P < 0. 05）. The number of mice through target quadrant and t /t in Yishen Huazhuo Prescription group were significantly increased as compared with the SAMP8 group（ P <0.05）. The number of mice through target quadrant in the donepezil group was apparently increased as compared with the SAMP8 group（ P < 0. 05）. Under electron microscope

the brain samples of mice in SAMR1 group showed that synaptic clefts of hippocampal neuron were clear

presynaptic mitochondrial cristae and membrane were complete

and synaptic vesicle count was normal with average size. While in the SAMP8 group

synaptic cleft was indistinct and completely fused

presynaptic swelling occurred with no mitochondria

and synaptic vesicle count was dramatically decreased with different sizes. In Yishen Huazhuo Prescription group

small part of synaptic cleft was fused

presynaptic swelling was relieved

and the relief degree of synaptic damage was better than that in the donepezil group. Comparing with the SAMR1 group

CREB expression of hippocampus in the SAMP8 group was obviously decreased（ P < 0. 05）. Yishen Huazhuo Prescription and donepezil could up-regulate the expression of CREB（ P <0. 05）. Conclusion Yishen Huazhuo Prescription can significantly improve learning and memory ability of SAMP8 mice. The possible mechanism may be related to the up-regulation of CREB protein expression in hippocampus

protection effect on microstructure of hippocampus neuronal synapse and function improvement of neuronal synapse.