Next Article in Journal
Diet Quality—The Greeks Had It Right!
Previous Article in Journal
Paradoxical Effects of Fruit on Obesity
Open AccessCommunication

The Identification of Biochanin A as a Potent and Selective β-Site App-Cleaving Enzyme 1 (Bace1) Inhibitor

by Kumju Youn 1,†, Ji-Hyun Park 1,†, Jinhyuk Lee 2,3, Woo-Sik Jeong 4,*, Chi-Tang Ho 5 and Mira Jun 1,6,*
1
Department of Food Science and Nutrition, Dong-A University, Busan 604-714, Korea
2
Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea
3
Department of Bioinformatics, University of Sciences and Technology, Daejeon 305-350, Korea
4
Department of Food & Life Science, College of Biomedical Science & Engineering, Inje University, Gimhae 621-749, Korea
5
Department of Food Science, Rutgers University, New Brunswick, NJ 08901, USA
6
Institute of Convergence Bio-Health (ICBH), Dong-A University, 32, Daeshingongwon-Ro, Seo-Gu, Busan 602-715, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2016, 8(10), 637; https://doi.org/10.3390/nu8100637
Received: 23 July 2016 / Revised: 1 October 2016 / Accepted: 10 October 2016 / Published: 14 October 2016
Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the enzyme involved in the abnormal production of the amyloidogenic peptide Aβ, one of the major causes of histological hallmarks of Alzheimer’s disease (AD). Thus, BACE1 represents a key target protein in the development of new potential target for the prevention and treatment of AD. In this study, in vitro anti-AD activity of biochanin A, a dietary isoflavone found in legumes and most notably red clover, were evaluated via human recombinant BACE1 inhibition assay, as well as enzyme kinetic and molecular docking predictions. Enzyme-based assays revealed that biochanin A exhibited a non-competitive inhibitory effect on BACE1 with an IC50 value of 28 μM and a Ki of 43 μM. In addition, docking simulation results demonstrated that ASN37, SER35, SER36, TRP76, and ARG128 residues of BACE1 interacted with biochanin A. Moreover, the binding energy of biochanin A was negative (−8.4 kcal/mol), indicating that it might potentiate a strong binding between the compound and the allosteric site of BACE1, resulting in further effective BACE1 inhibition. The present novel findings raise the possibility that biochanin A may be used as a preventative, developed into a therapeutic agent for AD, or both. View Full-Text
Keywords: Alzheimer’s disease; β-secretase (BACE1); β-amyloid peptide (Aβ); biochanin A Alzheimer’s disease; β-secretase (BACE1); β-amyloid peptide (Aβ); biochanin A
Show Figures

Figure 1

MDPI and ACS Style

Youn, K.; Park, J.-H.; Lee, J.; Jeong, W.-S.; Ho, C.-T.; Jun, M. The Identification of Biochanin A as a Potent and Selective β-Site App-Cleaving Enzyme 1 (Bace1) Inhibitor. Nutrients 2016, 8, 637.

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.

Article Access Map by Country/Region

1
Back to TopTop