Computer-aided identification of protein targets of four polyphenols in Alzheimer’s disease (AD) and validation in a mouse AD model

Abstract

Natural polyphenols are a large class of phytochemicals with neuroprotective effects. Four polyphenolic compounds: hesperidin, icariin, dihydromyricetin and baicalin were selected to evaluate their effects on Alzheimer’s disease (AD). We analyzed by an inverse docking procedure (INVDOCK) the potential protein targets of these polyphenols within the KEGG AD pathway. Consequently, their therapeutic effects were evaluated and compared in a transgenic APP/PS1 mouse model of AD. These polyphenols were docked to several targets, including APP, BACE, PSEN, IDE, CASP, calpain and TNF-α, suggesting potential in vivo activities. Five month old transgenic mice were treated with these polyphenols. Icariin and hesperidin restored behavioral deficits and ameliorated Aβ deposits in both the cortex and hippocampus while baicalin and dihydromyricetin showed no substantial effects. Our findings suggest that hesperidin and icariin could be considered potential therapeutic candidates of human AD.

Keywords

Alzheimer's disease / polyphenol / INVDOCK / cerebral amyloidosis / behavioral deficit

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Acknowledgments

The authors would like to thank Prof. M. Jucker for providing male transgenic APP/PS1-(21) mice. The study was supported by the China Scholarship Council (CSC) and the Deutscher Akademischer Austausch-Dienst (DAAD). The authors declare there is no conflict of interest.

RIGHTS & PERMISSIONS

2018 2018 by the Journal of Biomedical Research.