期刊
CURRENT ALZHEIMER RESEARCH
卷 7, 期 2, 页码 126-133出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/156720510790691218
关键词
Hyperforin derivative; Alzheimer disease; spatial learning; neuropathological damage; amyloid-beta-peptide; oxidative damage; transgenic mice; St. John's wort
资金
- FONDAP [13980001]
- FONDEF [D03I 1002, D07I 1052]
- Millennium Institute for Fundamental Biology (MIFAB)
- CONICYT
- [PFB12/2007]
The use of natural compounds is an interesting stratagem in the search of drugs with therapeutic potential for the treatment of Alzheimer's disease (AD). We report here the effect of the hyperforin derivative (IDN5706, tetrahydrohyperforin), a semi-synthetic derivative of the St. John's Wort, on the brain neuropathology, learning and memory in a double transgenic (APPswe, PS-1dE9) mouse model of AD. Results indicate that, IDN5706 alleviates memory decline induced by amyloid-beta (A beta) deposits as indicated by the Morris water maze paradigm. Moreover, the analysis of A deposits by immunodetection and thioflavin-S staining of brain sections, only reveals a decrease in the frequency of the larger-size A beta deposits, suggesting that IDN5706 affected the turnover of amyloid plaques. Immunohistochemical analysis, using GFAP and n-Tyrosine indicated that the hyperforin derivative prevents the inflammatory astrocytic reaction and the oxidative damage triggered by high A beta deposit levels. We conclude that the hyperforin derivative, IDN5706, has therapeutic potential for prevention and treatment of AD.
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