Potentiating effect of glabridin from Glycyrrhiza glabra on GABAA receptors
| Autor: | Günter Gisselmann, Leopoldo Beltrán, Hanns Hatt, Katrin M. Hoffmann, Paul M. Ziemba |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Insomnia Protein subunit Biophysics Xenopus Anxiety Pharmacology Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Binding site Receptor Glycyrrhiza glabra biology Chemistry GABAA receptor GABAA Receptor Long-term potentiation biology.organism_classification 030104 developmental biology Xenopus Oocytes Glycyrrhiza 030217 neurology & neurosurgery Glabridin |
| Zdroj: | Biochemistry and Biophysics Reports. 6:197-202 |
| ISSN: | 2405-5808 |
| DOI: | 10.1016/j.bbrep.2016.04.007 |
| Popis: | Extracts from Glycyrrhiza are traditionally used for the treatment of insomnia and anxiety. Glabridin is one of the main flavonoid compounds from Glycyrrhiza glabra and displays a broad range of biological properties. In the present work, we investigated the effect of glabridin on GABA A receptors. For this purpose, we employed the two-electrode voltage-clamp technique on Xenopus laevis oocytes expressing recombinant GABA A receptors. Through this approach, we observed that glabridin presents a strong potentiating effect on GABA A α1β(1−3)γ2 receptors. The potentiation was slightly dependent on the β subunit and was most pronounced at the α1β2γ2 subunit combination, which forms the most abundant GABA A receptor in the CNS. Glabridin potentiated with an EC 50 of 6.3±1.7 µM and decreased the EC 50 of the receptor for GABA by approximately 12-fold. The potentiating effect of glabridin is flumazenil-insensitive and does not require the benzodiazepine binding site. Glabridin acts on the β subunit of GABA A receptors by a mechanism involving the M286 residue, which is a key amino acid at the binding site for general anesthetics, such as propofol and etomidate. Our results demonstrate that GABA A receptors are strongly potentiated by one of the main flavonoid compounds from Glycyrrhiza glabra and suggest that glabridin could contribute to the reported hypnotic effect of Glycyrrhiza extracts. |
| Databáze: | OpenAIRE |
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