Protection against beta-amyloid peptide-induced memory impairment with long-term administration of extract of Angelica gigas or decursinol in mice.

We investigated the effect of long-term oral administration of ethanolic extract of Angelica gigas Nakai (Umbelliferae) (EAG) or decursinol, a coumarin isolated from A. gigas, on beta-amyloid peptide 1-42 (Abeta(1-42))-induced memory impairment in mice. Mice were allowed free access to drinking water (control) or water containing different concentrations of EAG. After 4 weeks, Abeta(1-42) (410 pmol) was administered via intracerebroventricular injection. Pretreatment of mice with EAG (0.1%) for 4 weeks significantly blocked the Abeta(1-42)-induced impairment in passive avoidance performance. Next, mice were fed with chow mixed with various doses of decursinol for 4 weeks before intracerebroventricular injection of Abeta(1-42) (410 pmol). Pretreatment of mice with decursinol (0.001%, 0.002%, and 0.004%) for 4 weeks significantly attenuated the Abeta(1-42)-induced impairment in passive avoidance performance. Decursinol (0.004%) also significantly blunted the Abeta(1-42)-induced decrease in alternation behavior (spatial working memory) in the Y-maze test without change in general locomotor activity. These findings suggest that EAG or decursinol may have preventive effect against memory impairment related with Abeta of Alzheimer's disease.