ABSTRACT
Phlorotannin supplement (PS) is a natural hypnotic substrate that modulates γ-aminobutyric acid type A (GABAA)-benzodiazepine (BZD) receptors. However, there is a lack of functional data assessing the role of individual components of PS, such as Dieckol, as allosteric activators of GABAA receptors (GABAAR). Using the whole cell patch clamp technique, we demonstrated that PS functionally enhanced the activity of GABAA-BZD receptors in a heterologous system and in primary cultured neurons. Application of diazepam (DZP) or Dieckol (1) increased GABAAR-mediated inward current in HEK293T cells containing the α1 subunit in a dose-dependent manner, (2) which was blocked by co-treatment with the selective benzodiazepine site antagonist, flumazenil (FLZ); it also (3) increased the amplitude of GABAA-BZD receptors in primary cultured neurons, which was blocked by FLZ and (4) attenuated spontaneous activity in cultured neurons. These results indicate that PS and Dieckol act as positive allosteric activators of GABAA-BZD receptors, which might be the underlying mechanism of the sedative-hypnotic effect of PS. To our knowledge, this is the first study to directly link Dieckol-induced GABAAR activation via the BZD site binding and suppression of spontaneous neuronal activity in vitro.
Acknowledgements
SK and JJ contributed equally to this work. SK, JJ, SC, and JL designed and contributed to manuscript drafting. JL managed the project. All authors reviewed the manuscript and approved the final version.
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No potential conflict of interest was reported by the authors.
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This article has been republished with minor changes. These changes do not impact the academic content of the article.
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Sangoh Kwon
Sangoh Kwon is Director of Research R&D center at S&D Research and Development Institute S&D Co., Ltd.
Jong Hoon Jung
Jong Hoon Jung is Researcher at Food Functional Evaluation Support Team, Korea Food Research Institute (KFRI).
Suengmok Cho
Seungmok Cho is Assistant Professor at the Department of Food Science and Technology, Pukyong National University.
Kwang-Deog Moon
Kwang-Deog Moon is Professor, Major in Food Biotechnology, School of Food Science & Biotechnology, Kyungpook National University.
Jaekwang Lee
Jaekwang Lee is a Senior Scientist at Research group of Functional Food Materials, Division of Food Functionality, Korea Food Research Institute (KFRI).