Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling Studies
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 (D...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-03-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1420-3049/23/4/785 |
| _version_ | 1817994337021067264 |
|---|---|
| author | Prashamsa Koirala Su Hui Seong Hyun Ah Jung Jae Sue Choi |
| author_facet | Prashamsa Koirala Su Hui Seong Hyun Ah Jung Jae Sue Choi |
| author_sort | Prashamsa Koirala |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T01:50:46Z |
| format | Article |
| id | doaj.art-6209c0cb95c34d46a06d28fdddc900b1 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-14T01:50:46Z |
| publishDate | 2018-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-6209c0cb95c34d46a06d28fdddc900b12022-12-22T02:19:21ZengMDPI AGMolecules1420-30492018-03-0123478510.3390/molecules23040785molecules23040785Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling StudiesPrashamsa Koirala0Su Hui Seong1Hyun Ah Jung2Jae Sue Choi3Department of Food and Life Science, Pukyong National University, Busan 48513, KoreaDepartment of Food and Life Science, Pukyong National University, Busan 48513, KoreaDepartment of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896, KoreaDepartment of Food and Life Science, Pukyong National University, Busan 48513, KoreaThe 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.http://www.mdpi.com/1420-3049/23/4/785cholinesteraseBACE1molecular dockingkineticsAlzheimer’s disease |
| spellingShingle | Prashamsa Koirala Su Hui Seong Hyun Ah Jung Jae Sue Choi Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling Studies Molecules cholinesterase BACE1 molecular docking kinetics Alzheimer’s disease |
| title | Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling Studies |
| title_full | Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling Studies |
| title_fullStr | Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling Studies |
| title_full_unstemmed | Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling Studies |
| title_short | Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling Studies |
| title_sort | comparative evaluation of the antioxidant and anti alzheimer s disease potential of coumestrol and puerarol isolated from pueraria lobata using molecular modeling studies |
| topic | cholinesterase BACE1 molecular docking kinetics Alzheimer’s disease |
| url | http://www.mdpi.com/1420-3049/23/4/785 |
| work_keys_str_mv | AT prashamsakoirala comparativeevaluationoftheantioxidantandantialzheimersdiseasepotentialofcoumestrolandpuerarolisolatedfrompuerarialobatausingmolecularmodelingstudies AT suhuiseong comparativeevaluationoftheantioxidantandantialzheimersdiseasepotentialofcoumestrolandpuerarolisolatedfrompuerarialobatausingmolecularmodelingstudies AT hyunahjung comparativeevaluationoftheantioxidantandantialzheimersdiseasepotentialofcoumestrolandpuerarolisolatedfrompuerarialobatausingmolecularmodelingstudies AT jaesuechoi comparativeevaluationoftheantioxidantandantialzheimersdiseasepotentialofcoumestrolandpuerarolisolatedfrompuerarialobatausingmolecularmodelingstudies |