Next Article in Journal
(−)-Epicatechin Reduces Blood Pressure and Improves Left Ventricular Function and Compliance in Deoxycorticosterone Acetate-Salt Hypertensive Rats
Next Article in Special Issue
Valorization of Olive Pomace-Based Nutraceuticals as Antioxidants in Chemical, Food, and Biological Models
Previous Article in Journal
Proanthocyanidins Protect Epithelial Cells from Zearalenone-Induced Apoptosis via Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis Pathways in Mouse Small Intestines
Previous Article in Special Issue
Application of a JA-Ile Biosynthesis Inhibitor to Methyl Jasmonate-Treated Strawberry Fruit Induces Upregulation of Specific MBW Complex-Related Genes and Accumulation of Proanthocyanidins
Article Menu
Issue 7 (July) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(7), 1509;

In Silico Docking and In Vitro Approaches towards BACE1 and Cholinesterases Inhibitory Effect of Citrus Flavanones

Department of Food Science and Nutrition, Dong-A University, 37, Nakdong-daero 550 beon-gil, Saha-gu, Busan 49315, Korea
Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125, Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea
Department of Bioinformatics, KIRBB School of Bioscience, Korea University of Sciences and Technology, 217 Gajung-ro, Yuseong-gu, Daejeon 34113, Korea
Author to whom correspondence should be addressed.
Academic Editor: Francesca Giampieri
Received: 27 May 2018 / Revised: 19 June 2018 / Accepted: 19 June 2018 / Published: 22 June 2018
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
Full-Text   |   PDF [3333 KB, uploaded 22 June 2018]   |  


Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease, distinctively characterized by senile plaques, neurofibrillary tangles, and synaptic loss, finally resulting in neuronal death. β-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) and cholinesterases have been identified as therapeutic targets for AD, and the discovery of their inhibitors is of critical importance for developing preventive strategies for AD. To discover natural multi-target compounds possessing BACE1, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory properties, major citrus flavanones including hesperetin, naringenin, and hesperidin were evaluated. In vitro anti-AD activities were performed via BACE1 and cholinesterases inhibition assays, as well as enzyme kinetic predictions. For the design of potential inhibitors of AD-related enzymes, molecular docking analysis was performed. Based on the biological evaluation, hesperidin demonstrated the best inhibitory properties toward BACE1, AChE, and BChE, with IC50 values of 10.02 ± 1.12, 22.80 ± 2.78, and 48.09 ± 0.74 µM, respectively. Kinetic studies revealed that all tested compounds were found to be noncompetitive inhibitors against BACE1 and cholineseterases. In addition, molecular docking studies of these compounds demonstrated negative binding energies for BACE1, AChE, and BChE, indicating high affinity and tight binding capacity for the target enzymes. The present study suggested that the selected citrus flavanones could act together as multiple inhibitors of BACE1, AChE, and BChE, indicating preventive and therapeutic potential against AD. View Full-Text
Keywords: Alzheimer’s disease; BACE1; cholinesterases; in silico docking; citrus flavanones; hesperidin Alzheimer’s disease; BACE1; cholinesterases; in silico docking; citrus flavanones; hesperidin

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Lee, S.; Youn, K.; Lim, G.; Lee, J.; Jun, M. In Silico Docking and In Vitro Approaches towards BACE1 and Cholinesterases Inhibitory Effect of Citrus Flavanones. Molecules 2018, 23, 1509.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top