Title: Computer-aided identification of protein targets of four polyphenols in Alzheimers disease (AD) and validation in a mouse AD model

 

Authors: Chaoyun Li1, Ping Meng2, Benzheng Zhang2, Hong Kang3, Hanli Wen2, Hermann Schluesener1, Zhiwei Cao3, Zhiyuan Zhang2

 

Institutions: 1Institute of Pathology and Neuropathology, University of Tuebingen, Tuebingen D-72076, Germany; 2Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 211166, China; 3School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.

 

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 Alzheimers 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

 

Full Text: JBR-2018-0021.pdf

 

J Biomed Res published on 30 June 2018, https://doi.org/10.7555/JBR.32.20180021