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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...

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Autores principales: Liu, Yang, Zhou, Xue, Zhou, Dan, Jian, Yongxing, Jia, Jingfu, Ge, Fahuan
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
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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.
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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
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