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Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling Studies

1
Department of Food and Life Science, Pukyong National University, Busan 48513, Korea
2
Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 13 March 2018 / Revised: 24 March 2018 / Accepted: 28 March 2018 / Published: 28 March 2018
(This article belongs to the Section Natural Products Chemistry)
The current study assesses the antioxidant effects of two similar isoflavonoids isolated from Pueraria lobata, coumestrol and puerarol, along with the cholinergic and amyloid-cascade pathways to mitigate Alzheimer’s disease (AD). Antioxidant activity was evaluated via 1,1-diphenyl-2-picryhydrazyl (DPPH) and peroxynitrite (ONOO) scavenging ability further screened via ONOO-mediated nitrotyrosine. Similarly, acetyl- and butyrylcholinesterase (AChE/BChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities were assessed together with docking and kinetic studies. Considering DPPH and ONOO scavenging activity, coumestrol (EC50 values of 53.98 and 1.17 µM) was found to be more potent than puerarol (EC50 values of 82.55 and 6.99 µM) followed by dose dependent inhibition of ONOO-mediated nitrotyrosine. Coumestrol showed pronounced AChE and BChE activity with IC50 values of 42.33 and 24.64 µM, respectively, acting as a dual cholinesterase (ChE) inhibitor. Despite having weak ChE inhibitory activity, puerarol showed potent BACE1 inhibition (28.17 µM). Kinetic studies of coumestrol showed AChE and BChE inhibition in a competitive and mixed fashion, whereas puerarol showed mixed inhibition for BACE1. In addition, docking simulations demonstrated high affinity and tight binding capacity towards the active site of the enzymes. In summary, we undertook a comparative study of two similar isoflavonoids differing only by a single aliphatic side chain and demonstrated that antioxidant agents coumestrol and puerarol are promising, potentially complementary therapeutics for AD. View Full-Text
Keywords: cholinesterase; BACE1; molecular docking; kinetics; Alzheimer’s disease cholinesterase; BACE1; molecular docking; kinetics; Alzheimer’s disease
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MDPI and ACS Style

Koirala, P.; Seong, S.H.; Jung, H.A.; Choi, J.S. Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling Studies. Molecules 2018, 23, 785. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23040785

AMA Style

Koirala P, Seong SH, Jung HA, Choi JS. Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling Studies. Molecules. 2018; 23(4):785. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23040785

Chicago/Turabian Style

Koirala, Prashamsa, Su H. Seong, Hyun A. Jung, and Jae S. Choi 2018. "Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling Studies" Molecules 23, no. 4: 785. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23040785

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