In China, herbal medicine has an extensive history for the treatment of cerebrovascular diseases. Clinical studies have shown that stroke patients are more likely to experience significant memory decline in comparison to their healthy counterparts. Cognition is improved in stroke patients treated with herbal medicine active components, Geniposide (GP) and Geniposide Rg1 (GRg1) (together, called TLJN). However, the effect of TLJN in Alzheimer disease remains unknown. Therefore, we investigated the behavioral effect of TLJN in male and female APP/V717I transgenic (Tg) mice. We conducted two different treatment strategies: (1) pretreatment strategy: medically treated at the age of 3 months which lasted for 3 months; (2) early treatment strategy: medically treated at the age of 6 months which lasted for 4 months. In open field test, locomotor activity and anxiety-like behavior were not affected after TLJN administration in Tg mice. In Morris Water Maze test, spatial learning processes in both genders were improved by TLJN treatments. Furthermore, retrieval processes were significantly improved in the pretreatment strategy for only male mice, which also showed a trend for improved retrieval processes with early treatment. In the inhibitory avoidance test, TLJN enhanced learning processes. In addition, gender differences were found in Tg mice exposed to TLJN treatments. In Tg male mice, significant efficacy was seen at high and middle doses, and in Tg female mice, a low dose was more effective.
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