Green Tea and One of Its Constituents, Epigallocatechine-3-gallate, Are Potent Inhibitors of Human 11β-hydroxysteroid Dehydrogenase Type 1
Open accessAbstract
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.
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- Authors
- Hintzpeter, J., Stapelfeld, C., Loerz, C., Martin, H.-J., & Maser, E.
- Affiliations
- Christian-Albrechts-Universität zu Kiel (DE)
- Corresponding author
- Maser, Edmund
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-01-03
- Volume
- 9
- Issue
- 1
- Pages
- e84468
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3880318
- OpenAlex
- W2005151269
- Cited by
- 53
- References
- 42
- Citations by year
- 2026: 3 · 2024: 7 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 4 · 2016: 2 · 2014: 5
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft (MA 1704/5-2)
- Bundesministerium für Bildung und Forschung (0315397A)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Tea Polyphenols and Effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Keywords
- green tea, epigallocatechin gallate, 11β-hydroxysteroid dehydrogenase type 1, enzyme inhibition, catechins, glucocorticoid metabolism, metabolic syndrome, type 2 diabetes, polyphenols, enzyme kinetics, molecular docking
- MeSH terms
- Catechin, Dose-Response Relationship, Drug, Enzyme Inhibitors, Humans, Hydrocortisone, Kinetics, Microsomes, Liver, Plant Extracts, Tea, 11-beta-Hydroxysteroid Dehydrogenase Type 1, 11-beta-Hydroxysteroid Dehydrogenase Type 2
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