Trans-2, 4-dimethoxystibene (S3) is a synthetic stilbenes. In the present study, S3 was investigated to assess its neuroprotective effect against the toxicity induced by Abeta(25-35) in hypercholesterolemic rats. Rats were fed with hypercholesterolemic chow for six weeks, and then received a single intracerebroventricular (i.c.v.) injection of Abeta(25-35) and a treatment with S3 or estradiol (E2). Behavioral changes and neuron apoptosis in rats were evaluated using Morris water maze, step-down test and TUNEL tests. To further explore the mechanism of S3, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), choline acetyl transferase (ChAT), acetylcholine esterase (AchE) and the contents of malondialdehyde (MDA) in hippocampus were analyzed by spectrophotometric method. At the same time, the releases of cytochrome C were analyzed by Western Blot, and the contents of acetylcholine (Ach) were analyzed by Elisa. The data showed that consumption of S3 (50mg/kg/d) significantly ameliorated the cognitive deficits and neuron apoptosis caused by i.c.v. injection of Abeta(25-35). Meanwhile, S3 reversed the decreased activity of ChAT, SOD, GSH-Px and contents of Ach, as well as the increased activity of AchE, MDA contents and the release of cytochrome C in hippocampus. These findings suggest that S3 may be a potential candidate for development as therapeutic agent to treat AD through regulating cholinergic nerve system and anti-oxidative mechanism.
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