Geniposide Effectively Reverses Cognitive Impairment and Inhibits Pathological Cerebral Damage by Regulating the mTOR Signal Pathway in APP∕PS1 Mice

Abstract Objective The aim of this study is to investigate the protective effects as well as the underlying molecular mechanisms of geniposide in APP/PS1 transgenic mice. Method APP/PS1 mice were subjected to intragastric administration of geniposide (50 mg/kg/d) for 8 weeks (including a 2-week behavior test). The novel object recognition (NOR) and the Morris water maze (MWM) tests were used for behavioral assessments. Aβ1-40 plaques in mice cortices and hippocampi are visualized with immunohistochemistical staining. ELISA was used to quantify the levels of soluble Aβ1-40 and Aβ1-42 in the hippocampus. Western blot was used to detect p-Akt/Akt, p-mTOR/mTOR and p-4E-BP1/4E-BP1 levels. The relative mRNA levels of Akt, mTOR and 4E-BP1 were quantified using real-time PCR (RT-PCR). Results Geniposide alleviated cognitive impairment by improving the ability of novel object exploration, spatial memory, and reduced the level of Aβ in the brain of APP/PS1 mice. Geniposide possibly regulates mTOR-related proteins through modification of phosphorylation. Geniposide markedly lowered p-mTOR and p-Akt expressions while elevating p-4E-BP1 expression. Geniposide obviously reduced the relative mRNA levels of Akt and mTOR and increased the relative mRNA level of 4E-BP1. Conclusion Geniposide is able to alleviate cognitive impairments and cerebral damage in APP/PS1 mice, with its neuroprotective effects likely mediated via modulation of the mTOR signaling pathway.