期刊
FRONTIERS IN PHARMACOLOGY
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2017.00340
关键词
Alzheimer's disease; axonal regeneration; CRMP2 phosphorylation; DARTS analysis; memory recovery; Drynaria rhizome
资金
- Institute of Natural Medicine at the University of Toyama
- University of Toyama
- Grants-in-Aid for Scientific Research [15H05268, 16H05276] Funding Source: KAKEN
Natural medicines are attractive sources of leading compounds that can be used as interventions for neurodegenerative disorders. The complexity of their chemical components and undetermined bio-metabolism have greatly hindered both the use of natural medicines and the identification of their active constituents. Here, we report a systematic strategy for evaluating the bioactive candidates in natural medicines used for Alzheimer's disease (AD). We found that Drynaria Rhizome could enhance memory function and ameliorate AD pathologies in 5XFAD mice. Biochemical analysis led to the identification of the bio-effective metabolites that are transferred to the brain, namely, naringenin and its glucuronides. To explore the mechanism of action, we combined the drug affinity responsive target stability with immunoprecipitationliquid chromatography/mass spectrometry analysis, identifying the collapsin response mediator protein 2 protein as a target of naringenin. Our study indicates that biochemical analysis coupled with pharmacological methods can be used in the search for new targets for AD intervention.
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