Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1.

The microsomal enzyme 11β-hydroxysteroid deydrogenase type 1 (11β-HSD1) catalyzes the interconversion of glucocorticoid receptor-inert cortisone to receptor- active cortisol, thereby acting as an intracellular switch for regulating the access of glucocorticoid hormones to the glucocorticoid receptor...

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Autores principales:	Jan Hintzpeter, Claudia Stapelfeld, Christine Loerz, Hans-Joerg Martin, Edmund Maser
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Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2bd96f7156d848a6bbb2e4f05a078c29
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spelling	oai:doaj.org-article:2bd96f7156d848a6bbb2e4f05a078c292021-11-18T08:38:58ZGreen tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1.1932-620310.1371/journal.pone.0084468https://doaj.org/article/2bd96f7156d848a6bbb2e4f05a078c292014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24404164/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The microsomal enzyme 11β-hydroxysteroid deydrogenase type 1 (11β-HSD1) catalyzes the interconversion of glucocorticoid receptor-inert cortisone to receptor- active cortisol, thereby acting as an intracellular switch for regulating the access of glucocorticoid hormones to the glucocorticoid receptor. There is strong evidence for an important aetiological role of 11β-HSD1 in various metabolic disorders including insulin resistance, diabetes type 2, hypertension, dyslipidemia and obesity. Hence, modulation of 11β-HSD1 activity with selective inhibitors is being pursued as a new therapeutic approach for the treatment of the metabolic syndrome. Since tea has been associated with health benefits for thousands of years, we sought to elucidate the active principle in tea with regard to diabetes type 2 prevention. Several teas and tea specific polyphenolic compounds were tested for their possible inhibition of cortisone reduction with human liver microsomes and purified human 11β-HSD1. Indeed we found that tea extracts inhibited 11β-HSD1 mediated cortisone reduction, where green tea exhibited the highest inhibitory potency with an IC50 value of 3.749 mg dried tea leaves per ml. Consequently, major polyphenolic compounds from green tea, in particular catechins were tested with the same systems. (-)-Epigallocatechin gallate (EGCG) revealed the highest inhibition of 11β-HSD1 activity (reduction: IC50 = 57.99 µM; oxidation: IC50 = 131.2 µM). Detailed kinetic studies indicate a direct competition mode of EGCG, with substrate and/or cofactor binding. Inhibition constants of EGCG on cortisone reduction were Ki = 22.68 µM for microsomes and Ki = 18.74 µM for purified 11β-HSD1. In silicio docking studies support the view that EGCG binds directly to the active site of 11β-HSD1 by forming a hydrogen bond with Lys187 of the catalytic triade. Our study is the first to provide evidence that the health benefits of green tea and its polyphenolic compounds may be attributed to an inhibition of the cortisol producing enzyme 11β-HSD1.Jan HintzpeterClaudia StapelfeldChristine LoerzHans-Joerg MartinEdmund MaserPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e84468 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jan Hintzpeter Claudia Stapelfeld Christine Loerz Hans-Joerg Martin Edmund Maser Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1.
description	The microsomal enzyme 11β-hydroxysteroid deydrogenase type 1 (11β-HSD1) catalyzes the interconversion of glucocorticoid receptor-inert cortisone to receptor- active cortisol, thereby acting as an intracellular switch for regulating the access of glucocorticoid hormones to the glucocorticoid receptor. There is strong evidence for an important aetiological role of 11β-HSD1 in various metabolic disorders including insulin resistance, diabetes type 2, hypertension, dyslipidemia and obesity. Hence, modulation of 11β-HSD1 activity with selective inhibitors is being pursued as a new therapeutic approach for the treatment of the metabolic syndrome. Since tea has been associated with health benefits for thousands of years, we sought to elucidate the active principle in tea with regard to diabetes type 2 prevention. Several teas and tea specific polyphenolic compounds were tested for their possible inhibition of cortisone reduction with human liver microsomes and purified human 11β-HSD1. Indeed we found that tea extracts inhibited 11β-HSD1 mediated cortisone reduction, where green tea exhibited the highest inhibitory potency with an IC50 value of 3.749 mg dried tea leaves per ml. Consequently, major polyphenolic compounds from green tea, in particular catechins were tested with the same systems. (-)-Epigallocatechin gallate (EGCG) revealed the highest inhibition of 11β-HSD1 activity (reduction: IC50 = 57.99 µM; oxidation: IC50 = 131.2 µM). Detailed kinetic studies indicate a direct competition mode of EGCG, with substrate and/or cofactor binding. Inhibition constants of EGCG on cortisone reduction were Ki = 22.68 µM for microsomes and Ki = 18.74 µM for purified 11β-HSD1. In silicio docking studies support the view that EGCG binds directly to the active site of 11β-HSD1 by forming a hydrogen bond with Lys187 of the catalytic triade. Our study is the first to provide evidence that the health benefits of green tea and its polyphenolic compounds may be attributed to an inhibition of the cortisol producing enzyme 11β-HSD1.
format	article
author	Jan Hintzpeter Claudia Stapelfeld Christine Loerz Hans-Joerg Martin Edmund Maser
author_facet	Jan Hintzpeter Claudia Stapelfeld Christine Loerz Hans-Joerg Martin Edmund Maser
author_sort	Jan Hintzpeter
title	Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1.
title_short	Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1.
title_full	Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1.
title_fullStr	Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1.
title_full_unstemmed	Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1.
title_sort	green tea and one of its constituents, epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/2bd96f7156d848a6bbb2e4f05a078c29
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Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1.

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