Objective To investigate the effects of naringin and the combined application of naringin with evodiamine on cognitive ability in APP^swe/PSΔE9 transgenic mice, and to compare the difference of neuroprotective effects between the applications of these two drugs alone or in combination, and to determine whether there is synergistic or additive effect of the combination of naringin and evodiamine. Methods ① APP^swe/PSΔE9 transgenic mice aged 3 months and 5 months were randomly divided into different groups, 12 in each group. The mice performed Morris water maze test after administration of the drugs for 4 weeks and 16 weeks, respectively. The drugs were mixed in the diet singly or in combination according to the grouping protocol. One group was used as vehicle group and one group was used as Aricept group. The littermates receiving placebo were used as normal control. ②The senile plaques were detected by Thioflavin-S staining and visualized directly by fluorescence microscopy. Results ① Compared with the APP^swe/PSΔE9 transgenic mice, naringin administrated alone for 4 weeks and 16 weeks showed a significantly decreased latency by 22% and 32%, respectively; and evodiamine administrated alone for 4 weeks and 16 weeks showed a decreased latency by 33% and 10%, respectively. ② The senile plaques were decreased by 26% in the hippocampus of mice after 16 weeks naringin administration. ③ The combined application of naringin with evodiamine showed the decreased latency by 47%, compared with the APP^swe/PSΔE9 transgenic mice, however, when compared with naringin alone, the combined application showed no more decreased latency. ConclusionsEither naringin or evodiamine can improve the cognitive deficits in APP^swe/PSΔE9 transgenic mice. Long-term effect of naringin is obviously better than its short-term effect. However, on the contrary, short-time use of evodiamine is effective but its long-time effect is decreased. The combined application of naringin with evodiamine can obviously improve the cognitive ability in APP^swe/PSΔE9 transgenic mice, however, it shows no synergetic protective effect compared with the use of naring in alone. 