Kessler Artur, Sahin-Nadeem Hilal, Lummis Sarah C R, Weigel Ingrid, Pischetsrieder Monika, Buettner Andrea, Villmann Carmen
Department of Chemistry and Pharmacy, Food Chemistry Division, University of Erlangen-Nuernberg, Erlangen, Germany.
Mol Nutr Food Res. 2014 Apr;58(4):851-62. doi: 10.1002/mnfr.201300420. Epub 2013 Nov 24.
GABAA receptors are modulated by Sideritis extracts. The aim of this study was to identify single substances from Sideritis extracts responsible for GABAA receptor modulation.
Single volatile substances identified by GC have been tested in two expression systems, Xenopus oocytes and human embryonic kidney cells. Some of these substances, especially carvacrol, were highly potent on GABAA receptors composed of α1β2 and α1β2γ2 subunits. All effects measured were independent from the presence of the γ2 subunit. As Sideritis extracts contain a high amount of terpenes, 13 terpenes with similar structure elements were tested in the same way. Following a prescreening on α1β2 GABAA 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 GABAA receptor function.
Comparing the chemical structures, the action of terpenes on GABAA 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.
希腊铁线莲提取物可调节GABAA受体。本研究的目的是从希腊铁线莲提取物中鉴定出负责调节GABAA受体的单一物质。
通过气相色谱法鉴定出的单一挥发性物质已在两种表达系统中进行了测试，即非洲爪蟾卵母细胞和人胚肾细胞。其中一些物质，尤其是香芹酚，对由α1β2和α1β2γ2亚基组成的GABAA受体具有高效能作用。所测量的所有效应均与γ2亚基的存在无关。由于希腊铁线莲提取物含有大量萜类化合物，因此以同样的方式测试了13种具有相似结构元素的萜类化合物。在对α1β2 GABAA受体进行预筛选后，采用高通量方法鉴定对转染细胞系中表达的α1β2γ2受体的GABA亲和力最有效的萜类物质。异胡薄荷醇、松樟醇、马鞭草烯醇和桃金娘烯醇是GABAA受体功能最有效的调节剂。
比较化学结构，萜类化合物对GABAA受体的作用很可能是由于所测试物质中存在羟基和双环结构。我们提出一种与γ2亚基无关且类似于醇类和麻醉剂作用的变构调节。
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