The Identification of Biochanin A as a Potent and Selective β-Site App-Cleaving Enzyme 1 (Bace1) Inhibitor
AbstractBeta-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
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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.
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(10):637.Chicago/Turabian Style
Youn, Kumju; Park, Ji-Hyun; Lee, Jinhyuk; Jeong, Woo-Sik; Ho, Chi-Tang; Jun, Mira. 2016. "The Identification of Biochanin A as a Potent and Selective β-Site App-Cleaving Enzyme 1 (Bace1) Inhibitor." Nutrients 8, no. 10: 637.
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