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Aim: To investigate the effect ofjujuboside A (JuA) on modulating gene expres-sion in the hippocampus. Methods: The spontaneous activity of mice was monitored, and the differential display polymerase chain reaction was adapted to screen differentially-expressed genes modulated by JuA in the mouse hippocampus.Results: JuA significantly decreased the total activity intensity (P＜0.01 vs control) at a dosage of 80 mg/kg, and the genes MAP/microtubule affinity-regulating kinase3 (Mark3) and retinitis pigmentosa GTPase regulator interacting proteinl(Rpgripl) were upregulated by JuA in the mouse hippocampus. Conclusion: JuA had an inhibitory effect on the spontaneous activity of the mice, and JuA regu-lated the transcription of Mark3 and Rpgripl in the mouse hippocampus.