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Acetylcholinesterase Inhibitor (AchEI) is the most extensive in all anti-dementia drugs.The extracts and isolated compounds from the Valeriana genus have shown anti-dementia bioactivity.Four new sesquiterpenoids (1-4) and a new monoterpenoid (5) were isolated from the root of Valeriana officinalis var.latiofolia.The acetylcholinesterase (AchE) inhibitory activity of isolates was evaluated by modified Ellman method in vitro.Learning and memory ability of compound 4 on mice was evaluated by the Morris water maze.The contents of acetylcholine (Ach), acetylcholine transferase (ChAT) and AchE in mice brains were determined by colorimetry.The results showed IC50 of compound 4 was 0.161 μM in vitro.Compared with the normal group, the learning and memory ability of mice and the contents of Ach and ChAT decreased in model group mice (P < 0.01), while the AchE increased (P < 0.01).Compared with the model group, Ach and ChAT in the positive control group, the high-dose group and the medium-dose group increased (P < 0.01), while the AchE decreased (P < 0.01).Compound 4 can improve the learning and memory abilities of APPswe/PS△E9 double-transgenic mice, and the mechanism may be related to the regulation of the relative enzyme in the cholinergic system.