期刊
NEUROSCIENCE LETTERS
卷 444, 期 3, 页码 280-285出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2008.08.052
关键词
Fisetin; Flavonoids; Amyloid beta protein; Alzheimer's disease
资金
- MEXT.HAITEKU
- apan Society for the Promotion of Science (JSPS)
Fisetin (3,3',4',7-tetrahydroxyflavone) has been found to be neuroprotective, induce neuronal differentiation, enhance memory, and inhibit the aggregation of the amyloid beta protein (A beta) that may cause the progressive neuronal loss in Alzheimer's disease. The diverse collection of biological activities of this compound may lead to a new type of therapeutic drug for Alzheimer's disease. As the first step to design even more effective drugs based upon the structure of fisetin, the present study investigated the Structural requirements for the anti-amyloidogenic activity of fisetin by comparing the effects of several structurally related flavonoids on A beta fibril formation in vitro. A beta 1-42 (20 mu M) and the flavonoids were incubated for 0-48 h at 37 degrees C, and fibril formation was quantitatively determined by the thioflavin T fluorescence assay. Among ten flavonoids tested, fisetin, 3',4',7-trihydroxylflavone, 3,3',4'-trihydroxyflavone, luteolin, quercetin and myricetin inhibited A beta fibril formation. On the other hand, 3,3',7-trihydroxyflavone, 5-deoxykaempferol, chrysin and kaempferol enhanced A beta fibril formation. These results suggest that the 3',4'-dihydroxyl group, but not the 3- or 7-hydroxyl group, is essential for the inhibitory effect of fisetin on A beta fibril formation. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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