Green Tea and One of Its Constituents, Epigallocatechine-3-gallate, Are Potent Inhibitors of Human 11 beta-hydroxysteroid Dehydrogenase Type 1

Hintzpeter, Jan, Stapelfeld, Claudia, Loerz, Christine, Martin, Hans-Joerg and Maser, Edmund (2014) Green Tea and One of Its Constituents, Epigallocatechine-3-gallate, Are Potent Inhibitors of Human 11 beta-hydroxysteroid Dehydrogenase Type 1 PLoS ONE, 9 (1).

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Abstract

The microsomal enzyme 11 beta-hydroxysteroid deydrogenase type 1 (11 beta-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 11 beta-HSD1 in various metabolic disorders including insulin resistance, diabetes type 2, hypertension, dyslipidemia and obesity. Hence, modulation of 11 beta-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 11 beta-HSD1. Indeed we found that tea extracts inhibited 11 beta-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. (2)Epigallocatechin gallate (EGCG) revealed the highest inhibition of 11 beta-HSD1 activity (reduction: IC50 = 57.99 mu M; oxidation: IC50 = 131.2 mu M). 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 mu M for microsomes and Ki = 18.74 mu M for purified 11 beta-HSD1. In silicio docking studies support the view that EGCG binds directly to the active site of 11 beta-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 11 beta-HSD1.

Document Type: Article
Additional Information: Times Cited: 2 0 2
Research affiliation: OceanRep > The Future Ocean - Cluster of Excellence
Kiel University
ISSN: 1932-6203
Projects: Future Ocean
Date Deposited: 30 Mar 2015 12:21
Last Modified: 30 Mar 2015 12:21
URI: http://eprints.uni-kiel.de/id/eprint/27722

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