Three-Step Test System for the Identification of Novel GABAA Receptor Modulating Food Plants
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Potentiation of γ-amino butyric acid (GABA)-induced GABAA receptor (GABAAR) activation is a common pathway to achieve sedative, sleep-enhancing, anxiolytic, and antidepressant effects. Presently, a three-component test system was established for the identification of novel GABAAR modulating food plants. In the first step, potentiation of GABA-induced response of the GABAAR was analysed by two-electrode voltage clamp (TEVC) for activity on human α1β2-GABAAR expressed in Xenopus laevis oocytes. Positively tested food plants were then subjected to quantification of GABA content by high-performance liquid chromatography with fluorescence detection (HPLC–FLD) to exclude test foods, which evoke a TEVC-response by endogenous GABA. In the third step, specificity of GABAA-modulating activity was assessed by TEVC analysis of Xenopus laevis oocytes expressing the homologous glycine receptor (GlyR). The three-component test was then applied to screen 10 aqueous extracts of food plants for their GABAAR activity. Thus, hop cones (Humulus lupulus) and Sideritis sipylea were identified as the most potent specific GABAAR modulators eliciting significant potentiation of the current by 182 ± 27 and 172 ± 19 %, respectively, at the lowest concentration of 0.5 μg/mL. The extracts can now be further evaluated by in vivo studies and by structural evaluation of the active components.
KeywordsGABAA receptor GABA Glycine receptor Sideritis Lemon balm leaves Hop cones
The scholarship grant by the Turkish Ministry of National Education for S. S. is gratefully acknowledged. We thank Hilal Sahin-Nadeem, Akdeniz University, for supplying Sideritis samples, Christoph Korbmacher from the Institute of Cellular and Molecular Physiology, FAU for providing Xenopus oocytes, Gabriele Fischer for performing the TLC analysis, and Christine Meißner for proof-reading the manuscript.
Compliance with Ethical Standards
Conflict of Interest
The scholarship grant by the Turkish Ministry of National Education for Sümeyye Sahin is gratefully acknowledged.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects.
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