Protective effects of trans-2, 4-dimethoxystibene on cognitive, impairments induced by Abeta(25-35) 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 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.
Ruan
Can-Jun
CJ
Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China. rcjjenny@msn.com
Li
Zhan
Z
Zhang
Li
L
Chen
Di-Hua
DH
Du
Guan-Hua
GH
Sun
Lan
L
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D016229:Amyloid beta-Peptides; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D058851:GPI-Linked Proteins; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D006937:Hypercholesterolemia / Q000503:physiopathology*; D007276:Injections, Intraventricular / Q000379:methods; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010446:Peptide Fragments; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013267:Stilbenes / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D016229:Amyloid beta-Peptides; D058851:GPI-Linked Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D013267:Stilbenes; C074636:amyloid beta-protein (25-35); C551998:trans-2,4-dimethoxystibene; D008315:Malondialdehyde; D045304:Cytochromes c; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; C548246:Ache protein, rat; D000109:Acetylcholine