title: The Identification of Biochanin A as a Potent and Selective β-Site App-Cleaving Enzyme 1 (Bace1) Inhibitor.
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 IC50value of 28 μM and aKiof 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.
authors.affiliation: Department of Food Science and Nutrition, Dong-A University, Busan 604-714, Korea. kjyoun@hanmail.net.
authors.forename: Kumju
authors.initials: K
authors.lastname: Youn
authors.affiliation: Department of Food Science and Nutrition, Dong-A University, Busan 604-714, Korea. jhpark9043@gmail.com.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea. mack97hyuk@gmail.com.|Department of Bioinformatics, University of Sciences and Technology, Daejeon 305-350, Korea. mack97hyuk@gmail.com.
authors.forename: Jinhyuk
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Food & Life Science, College of Biomedical Science & Engineering, Inje University, Gimhae 621-749, Korea. jeongws@inje.ac.kr.
authors.forename: Woo-Sik
authors.initials: WS
authors.lastname: Jeong
authors.affiliation: Department of Food Science, Rutgers University, New Brunswick, NJ 08901, USA. ho@aesop.rutgers.edu.
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.affiliation: Department of Food Science and Nutrition, Dong-A University, Busan 604-714, Korea. mjun@dau.ac.kr.|Institute of Convergence Bio-Health (ICBH), Dong-A University, 32, Daeshingongwon-Ro, Seo-Gu, Busan 602-715, Korea. mjun@dau.ac.kr.
authors.forename: Mira
authors.initials: M
authors.lastname: Jun
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007887:Fabaceae / Q000737:chemistry*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D019833:Genistein; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C004541:biochanin A
keywords: Alzheimer’s disease; biochanin A; β-amyloid peptide (Aβ); β-secretase (BACE1)