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Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies
Thrombin inhibition therapy is a practical strategy to reduce thrombotic and cardiovascular risks via blocking the formation of blood clots. This study aimed to identify naturally occurring thrombin inhibitors from licorice (one of the most popular edible herbs), as well as to investigate their inhi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9048847/ https://www.ncbi.nlm.nih.gov/pubmed/35492646 http://dx.doi.org/10.1039/c9ra09203j |
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author | Shi, Cheng-Cheng Chen, Tian-Ran Zhang, Qi-Hua Wei, Ling-Hua Huang, Chao Zhu, Ya-Di Liu, Hai-Bin Bai, Ya-Kun Wang, Fang-Jun Guo, Wen-Zhi Zhang, Li-Rong Ge, Guang-Bo |
author_facet | Shi, Cheng-Cheng Chen, Tian-Ran Zhang, Qi-Hua Wei, Ling-Hua Huang, Chao Zhu, Ya-Di Liu, Hai-Bin Bai, Ya-Kun Wang, Fang-Jun Guo, Wen-Zhi Zhang, Li-Rong Ge, Guang-Bo |
author_sort | Shi, Cheng-Cheng |
collection | PubMed |
description | Thrombin inhibition therapy is a practical strategy to reduce thrombotic and cardiovascular risks via blocking the formation of blood clots. This study aimed to identify naturally occurring thrombin inhibitors from licorice (one of the most popular edible herbs), as well as to investigate their inhibitory mechanisms. Among all tested licorice constituents, licochalcone A was found as the most efficacious agent against human thrombin (IC(50) = 7.96 μM). Inhibition kinetic analyses demonstrated that licochalcone A was a mixed inhibitor against thrombin-mediated Z-Gly-Gly-Arg-AMC acetate hydrolysis, with a K(i) value of 12.23 μM. Furthermore, mass spectrometry-based chemoproteomic assays and molecular docking simulations revealed that licochalcone A could bind to human thrombin at both exosite I and the catalytic site. In summary, our findings demonstrated that the chalcones isolated from licorice were a new class of direct thrombin inhibitors, also suggesting that licochalcone A was a promising lead compound for developing novel anti-thrombotic agents. |
format | Online Article Text |
id | pubmed-9048847 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-90488472022-04-28 Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies Shi, Cheng-Cheng Chen, Tian-Ran Zhang, Qi-Hua Wei, Ling-Hua Huang, Chao Zhu, Ya-Di Liu, Hai-Bin Bai, Ya-Kun Wang, Fang-Jun Guo, Wen-Zhi Zhang, Li-Rong Ge, Guang-Bo RSC Adv Chemistry Thrombin inhibition therapy is a practical strategy to reduce thrombotic and cardiovascular risks via blocking the formation of blood clots. This study aimed to identify naturally occurring thrombin inhibitors from licorice (one of the most popular edible herbs), as well as to investigate their inhibitory mechanisms. Among all tested licorice constituents, licochalcone A was found as the most efficacious agent against human thrombin (IC(50) = 7.96 μM). Inhibition kinetic analyses demonstrated that licochalcone A was a mixed inhibitor against thrombin-mediated Z-Gly-Gly-Arg-AMC acetate hydrolysis, with a K(i) value of 12.23 μM. Furthermore, mass spectrometry-based chemoproteomic assays and molecular docking simulations revealed that licochalcone A could bind to human thrombin at both exosite I and the catalytic site. In summary, our findings demonstrated that the chalcones isolated from licorice were a new class of direct thrombin inhibitors, also suggesting that licochalcone A was a promising lead compound for developing novel anti-thrombotic agents. The Royal Society of Chemistry 2020-01-22 /pmc/articles/PMC9048847/ /pubmed/35492646 http://dx.doi.org/10.1039/c9ra09203j Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Shi, Cheng-Cheng Chen, Tian-Ran Zhang, Qi-Hua Wei, Ling-Hua Huang, Chao Zhu, Ya-Di Liu, Hai-Bin Bai, Ya-Kun Wang, Fang-Jun Guo, Wen-Zhi Zhang, Li-Rong Ge, Guang-Bo Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies |
title | Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies |
title_full | Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies |
title_fullStr | Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies |
title_full_unstemmed | Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies |
title_short | Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies |
title_sort | inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9048847/ https://www.ncbi.nlm.nih.gov/pubmed/35492646 http://dx.doi.org/10.1039/c9ra09203j |
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