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

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

  • Nutrients. 2016 Oct 14;8(10):637. doi: 10.3390/nu8100637.
Kumju Youn 1,  Ji-Hyun Park 2,  Jinhyuk Lee 3 4,  Woo-Sik Jeong 5,  Chi-Tang Ho 6,  Mira Jun 7 8
Affiliations

Affiliations

  • 1 Department of Food Science and Nutrition, Dong-A University, Busan 604-714, Korea. kjyoun@hanmail.net.
  • 2 Department of Food Science and Nutrition, Dong-A University, Busan 604-714, Korea. jhpark9043@gmail.com.
  • 3 Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea. mack97hyuk@gmail.com.
  • 4 Department of Bioinformatics, University of Sciences and Technology, Daejeon 305-350, Korea. mack97hyuk@gmail.com.
  • 5 Department of Food & Life Science, College of Biomedical Science & Engineering, Inje University, Gimhae 621-749, Korea. jeongws@inje.ac.kr.
  • 6 Department of Food Science, Rutgers University, New Brunswick, NJ 08901, USA. ho@aesop.rutgers.edu.
  • 7 Department of Food Science and Nutrition, Dong-A University, Busan 604-714, Korea. mjun@dau.ac.kr.
  • 8 Institute of Convergence Bio-Health (ICBH), Dong-A University, 32, Daeshingongwon-Ro, Seo-Gu, Busan 602-715, Korea. mjun@dau.ac.kr.
PMID: 27754406 DOI: 10.3390/nu8100637
Abstract

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.

Keywords

Alzheimer’s disease; biochanin A; β-amyloid peptide (Aβ); β-secretase (BACE1).

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