Cargando…
Isolation of Chalcomoracin as a Potential α-Glycosidase Inhibitor from Mulberry Leaves and Its Binding Mechanism
Diabetes is a chronic metabolic disease, whereas α-glucosidases are key enzymes involved in the metabolism of starch and glycogen. There is a long history of the use of mulberry leaf (the leaf of Morus alba) as an antidiabetic herb in China, and we found that chalcomoracin, one of the specific Diels...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504037/ https://www.ncbi.nlm.nih.gov/pubmed/36144478 http://dx.doi.org/10.3390/molecules27185742 |
_version_ | 1784796115462258688 |
---|---|
author | Liu, Yang Zhou, Xue Zhou, Dan Jian, Yongxing Jia, Jingfu Ge, Fahuan |
author_facet | Liu, Yang Zhou, Xue Zhou, Dan Jian, Yongxing Jia, Jingfu Ge, Fahuan |
author_sort | Liu, Yang |
collection | PubMed |
description | Diabetes is a chronic metabolic disease, whereas α-glucosidases are key enzymes involved in the metabolism of starch and glycogen. There is a long history of the use of mulberry leaf (the leaf of Morus alba) as an antidiabetic herb in China, and we found that chalcomoracin, one of the specific Diels–Alder adducts in mulberry leaf, had prominent α-glucosidase inhibitory activity and has the potential to be a substitute for current hypoglycemic drugs such as acarbose, which have severe gastrointestinal side effects. In this study, chalcomoracin was effectively isolated from mulberry leaves, and its α-glucosidase inhibition was studied via enzymatic kinetics, isothermal titration (ITC) and molecular docking. The results showed that chalcomoracin inhibited α-glucosidase through both competitive and non-competitive manners, and its inhibitory activity was stronger than that of 1-doxymycin (1-DNJ) but slightly weaker than that of acarbose. ITC analysis revealed that the combination of chalcomoracin and α-glucosidase was an entropy-driven spontaneous reaction, and the molecular docking results also verified this conclusion. During the binding process, chalcomoracin went into the “pocket” of α-glucosidase via hydrophobic interactions, and it is linked with residues Val544, Asp95, Ala93, Gly119, Arg275 and Pro287 by hydrogen bonds. This study provided a potential compound for the prevention and treatment of diabetes and a theoretical basis for the discovery of novel candidates for α-glycosidase inhibitors. |
format | Online Article Text |
id | pubmed-9504037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95040372022-09-24 Isolation of Chalcomoracin as a Potential α-Glycosidase Inhibitor from Mulberry Leaves and Its Binding Mechanism Liu, Yang Zhou, Xue Zhou, Dan Jian, Yongxing Jia, Jingfu Ge, Fahuan Molecules Article Diabetes is a chronic metabolic disease, whereas α-glucosidases are key enzymes involved in the metabolism of starch and glycogen. There is a long history of the use of mulberry leaf (the leaf of Morus alba) as an antidiabetic herb in China, and we found that chalcomoracin, one of the specific Diels–Alder adducts in mulberry leaf, had prominent α-glucosidase inhibitory activity and has the potential to be a substitute for current hypoglycemic drugs such as acarbose, which have severe gastrointestinal side effects. In this study, chalcomoracin was effectively isolated from mulberry leaves, and its α-glucosidase inhibition was studied via enzymatic kinetics, isothermal titration (ITC) and molecular docking. The results showed that chalcomoracin inhibited α-glucosidase through both competitive and non-competitive manners, and its inhibitory activity was stronger than that of 1-doxymycin (1-DNJ) but slightly weaker than that of acarbose. ITC analysis revealed that the combination of chalcomoracin and α-glucosidase was an entropy-driven spontaneous reaction, and the molecular docking results also verified this conclusion. During the binding process, chalcomoracin went into the “pocket” of α-glucosidase via hydrophobic interactions, and it is linked with residues Val544, Asp95, Ala93, Gly119, Arg275 and Pro287 by hydrogen bonds. This study provided a potential compound for the prevention and treatment of diabetes and a theoretical basis for the discovery of novel candidates for α-glycosidase inhibitors. MDPI 2022-09-06 /pmc/articles/PMC9504037/ /pubmed/36144478 http://dx.doi.org/10.3390/molecules27185742 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Yang Zhou, Xue Zhou, Dan Jian, Yongxing Jia, Jingfu Ge, Fahuan Isolation of Chalcomoracin as a Potential α-Glycosidase Inhibitor from Mulberry Leaves and Its Binding Mechanism |
title | Isolation of Chalcomoracin as a Potential α-Glycosidase Inhibitor from Mulberry Leaves and Its Binding Mechanism |
title_full | Isolation of Chalcomoracin as a Potential α-Glycosidase Inhibitor from Mulberry Leaves and Its Binding Mechanism |
title_fullStr | Isolation of Chalcomoracin as a Potential α-Glycosidase Inhibitor from Mulberry Leaves and Its Binding Mechanism |
title_full_unstemmed | Isolation of Chalcomoracin as a Potential α-Glycosidase Inhibitor from Mulberry Leaves and Its Binding Mechanism |
title_short | Isolation of Chalcomoracin as a Potential α-Glycosidase Inhibitor from Mulberry Leaves and Its Binding Mechanism |
title_sort | isolation of chalcomoracin as a potential α-glycosidase inhibitor from mulberry leaves and its binding mechanism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504037/ https://www.ncbi.nlm.nih.gov/pubmed/36144478 http://dx.doi.org/10.3390/molecules27185742 |
work_keys_str_mv | AT liuyang isolationofchalcomoracinasapotentialaglycosidaseinhibitorfrommulberryleavesanditsbindingmechanism AT zhouxue isolationofchalcomoracinasapotentialaglycosidaseinhibitorfrommulberryleavesanditsbindingmechanism AT zhoudan isolationofchalcomoracinasapotentialaglycosidaseinhibitorfrommulberryleavesanditsbindingmechanism AT jianyongxing isolationofchalcomoracinasapotentialaglycosidaseinhibitorfrommulberryleavesanditsbindingmechanism AT jiajingfu isolationofchalcomoracinasapotentialaglycosidaseinhibitorfrommulberryleavesanditsbindingmechanism AT gefahuan isolationofchalcomoracinasapotentialaglycosidaseinhibitorfrommulberryleavesanditsbindingmechanism |