GABAA receptor modulation by terpenoids from Sideritis extracts. Issue 4 (24th November 2013)

• Record Type: Journal Article
• Authors: Kessler, Artur; Sahin‐Nadeem, Hilal; Lummis, Sarah C. R.; Weigel, Ingrid; Pischetsrieder, Monika; Buettner, Andrea; Villmann, Carmen
• Is Part Of: Molecular nutrition & food research. Volume 58:Issue 4(2014:Apr.)
• Page Start: 851
• Page End: 862
• Publication Date: 2013-11-24
• Subjects: Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201300420
• Languages: English
• ISSNs: 1613-4125

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="mnfr2113-sec-0010" sec-type="section"> <title>Scope</title> <p>GABA<sub>A</sub> receptors are modulated by <italic>Sideritis</italic> extracts. The aim of this study was to identify single substances from <italic>Sideritis</italic> extracts responsible for GABA<sub>A</sub> receptor modulation.</p> </sec> <sec id="mnfr2113-sec-0020" sec-type="section"> <title>Methods and results</title> <p>Single volatile substances identified by GC have been tested in two expression systems, <italic>Xenopus</italic> oocytes and human embryonic kidney cells. Some of these substances, especially carvacrol, were highly potent on GABA<sub>A</sub> receptors composed of α1β2 and α1β2γ2 subunits. All effects measured were independent from the presence of the γ2 subunit. As <italic>Sideritis</italic> extracts contain a high amount of terpenes, 13 terpenes with similar structure elements were tested in the same way. Following a prescreening on α1β2 GABA<sub>A</sub> receptors, a high‐throughput method was used for identification of the most effective terpenoid substances on GABA‐affinity of α1β2γ2 receptors expressed in transfected cell lines. Isopulegol, pinocarveol, verbenol, and myrtenol were the most potent modifiers of GABA<sub>A</sub> receptor function.</p> </sec> <sec id="mnfr2113-sec-0030" sec-type="section"> <title>Conclusion</title> <p>Comparing the chemical structures, the action of terpenes on GABA<sub>A</sub> receptors is most probably due to the presence of hydroxyl groups and a bicyclic character of the substances tested. We propose an allosteric modulation independent from the γ2 subunit and similar to the action of alcohols and anesthetics.</p> </sec> </abstract>