Biological and Computational Studies for Dual Cholinesterases Inhibitory Effect of Zerumbone
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) mediate the degradation of acetylcholine (ACh), a primary neurotransmitter in the brain. Cholinergic deficiency occurs during the progression of Alzheimer’s disease (AD), resulting in widespread cognitive dysfunction and decline. We evalua...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/12/5/1215 |
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| author | Jayeong Hwang Kumju Youn Yeongseon Ji Seonah Lee Gyutae Lim Jinhyuk Lee Chi-Tang Ho Sun-Hee Leem Mira Jun |
| author_facet | Jayeong Hwang Kumju Youn Yeongseon Ji Seonah Lee Gyutae Lim Jinhyuk Lee Chi-Tang Ho Sun-Hee Leem Mira Jun |
| author_sort | Jayeong Hwang |
| collection | DOAJ |
| description | Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) mediate the degradation of acetylcholine (ACh), a primary neurotransmitter in the brain. Cholinergic deficiency occurs during the progression of Alzheimer’s disease (AD), resulting in widespread cognitive dysfunction and decline. We evaluated the potential effect of a natural cholinesterase inhibitor, zerumbone, using in vitro target enzyme assays, as well as in silico docking and ADMET (absorption, distribution, metabolism, excretion, and toxicity) simulation. Zerumbone showed a predominant cholinesterase inhibitory property with IC<sub>50</sub> values of 2.74 ± 0.48 µM and 4.12 ± 0.42 µM for AChE and BChE, respectively; however, the modes of inhibition were different. Computational docking simulation indicated that Van der Waals interactions between zerumbone and both the cholinesterases were the main forces responsible for its inhibitory effects. Furthermore, zerumbone showed the best physicochemical properties for both bioavailability and blood–brain barrier (BBB) permeability. Together, in the present study, zerumbone was clearly identified as a unique dual AChE and BChE inhibitor with high permeability across the BBB, suggesting a strong potential for its physiological benefits and/or pharmacological efficacy in the prevention of AD. |
| first_indexed | 2024-03-10T20:13:44Z |
| format | Article |
| id | doaj.art-85e00c535482489ba6a542c9eb789b51 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T20:13:44Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
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| series | Nutrients |
| spelling | doaj.art-85e00c535482489ba6a542c9eb789b512023-11-19T22:43:58ZengMDPI AGNutrients2072-66432020-04-01125121510.3390/nu12051215Biological and Computational Studies for Dual Cholinesterases Inhibitory Effect of ZerumboneJayeong Hwang0Kumju Youn1Yeongseon Ji2Seonah Lee3Gyutae Lim4Jinhyuk Lee5Chi-Tang Ho6Sun-Hee Leem7Mira Jun8Department of Food Science and Nutrition, Dong-A University, Busan 49315, KoreaDepartment of Food Science and Nutrition, Dong-A University, Busan 49315, KoreaDepartment of Food Science and Nutrition, Dong-A University, Busan 49315, KoreaDepartment of Food Science and Nutrition, Dong-A University, Busan 49315, KoreaKorean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, KoreaKorean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, KoreaDepartment of Food Science, Rutgers University, New Brunswick, NJ 08901, USADepartment of Biological Science, Dong-A University, Busan 49315, KoreaDepartment of Food Science and Nutrition, Dong-A University, Busan 49315, KoreaAcetylcholinesterase (AChE) and butyrylcholinesterase (BChE) mediate the degradation of acetylcholine (ACh), a primary neurotransmitter in the brain. Cholinergic deficiency occurs during the progression of Alzheimer’s disease (AD), resulting in widespread cognitive dysfunction and decline. We evaluated the potential effect of a natural cholinesterase inhibitor, zerumbone, using in vitro target enzyme assays, as well as in silico docking and ADMET (absorption, distribution, metabolism, excretion, and toxicity) simulation. Zerumbone showed a predominant cholinesterase inhibitory property with IC<sub>50</sub> values of 2.74 ± 0.48 µM and 4.12 ± 0.42 µM for AChE and BChE, respectively; however, the modes of inhibition were different. Computational docking simulation indicated that Van der Waals interactions between zerumbone and both the cholinesterases were the main forces responsible for its inhibitory effects. Furthermore, zerumbone showed the best physicochemical properties for both bioavailability and blood–brain barrier (BBB) permeability. Together, in the present study, zerumbone was clearly identified as a unique dual AChE and BChE inhibitor with high permeability across the BBB, suggesting a strong potential for its physiological benefits and/or pharmacological efficacy in the prevention of AD.https://www.mdpi.com/2072-6643/12/5/1215ADMETAlzheimer’s disease (AD)cholinesterasescomputational docking simulationzerumbone |
| spellingShingle | Jayeong Hwang Kumju Youn Yeongseon Ji Seonah Lee Gyutae Lim Jinhyuk Lee Chi-Tang Ho Sun-Hee Leem Mira Jun Biological and Computational Studies for Dual Cholinesterases Inhibitory Effect of Zerumbone Nutrients ADMET Alzheimer’s disease (AD) cholinesterases computational docking simulation zerumbone |
| title | Biological and Computational Studies for Dual Cholinesterases Inhibitory Effect of Zerumbone |
| title_full | Biological and Computational Studies for Dual Cholinesterases Inhibitory Effect of Zerumbone |
| title_fullStr | Biological and Computational Studies for Dual Cholinesterases Inhibitory Effect of Zerumbone |
| title_full_unstemmed | Biological and Computational Studies for Dual Cholinesterases Inhibitory Effect of Zerumbone |
| title_short | Biological and Computational Studies for Dual Cholinesterases Inhibitory Effect of Zerumbone |
| title_sort | biological and computational studies for dual cholinesterases inhibitory effect of zerumbone |
| topic | ADMET Alzheimer’s disease (AD) cholinesterases computational docking simulation zerumbone |
| url | https://www.mdpi.com/2072-6643/12/5/1215 |
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