Title: Computer-aided identification of protein targets of four poly-phenols in Alzheimers disease and their protective effects in its mouse 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, Calwer Street 3, D-72076 Tuebingen, Germany; 2Department of Pathology, Nanjing Medical University, Longmian Avenue 101, Nanjing 211166, China; 3School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.

 

Abstract: Natural polyphenols, most common compounds of foods and herbal beverages, are a large class of phytochemical 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, therapeutic effects of them 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. 5-Months old transgenic mice were treated with these polyphenols, baicalin and dihydromyricetin showed no substantial effects, while icariin and hesperidin restored behavioral deficits and ameliorated Aβ deposits in both cortex and hippocampus. Our findings suggest that hesperidin and icariin might be considered potential therapeutic candidates of human AD or even other neurodegenerative diseases.

 

Keywords: Alzheimer's disease, polyphenol, INVDOCK, cerebral amyloidosis, behavioral deficit

 

Full Text: JBR-2018-0021 pre-proof.pdf

 

J Biomed Res published on June 5, https://doi.org/10.7555/JBR.32.20180021