Protective effects of trans-2, 4-dimethoxystibene on cognitive, impairments induced by Aβ25–35 in, hypercholesterolemic rats

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 Aβ25–35 in hypercholesterolemic rats. Rats were fed with hypercholesterolemic chow for six weeks, and then received a single intracerebroventricular (i.c.v.) injection of Aβ25–35 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 (50 mg/kg/d) significantly ameliorated the cognitive deficits and neuron apoptosis caused by i.c.v. injection of Aβ25–35. 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.