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      Sedative-Hypnotic and Receptor Binding Studies of Fermented Marine Organisms

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          Abstract

          This study was performed to investigate the sedative-hypnotic activity of γ-aminobutyric acid (GABA)-enriched fermented marine organisms (FMO), including sea tangle (FST) and oyster (FO) by Lactobacillus brevis BJ20 (L. brevis BJ20). FST and FO were tested for their binding activity of the GABA A-benzodiazepine and 5-HT 2C receptors, which are well-known molecular targets for sleep aids. We also measured the sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of FST and FO. In GABA A and 5-HT 2C receptor binding assays, FST displayed an effective concentration-dependent binding affinity to GABA A receptor, similar to the binding affinity to 5-HT 2C receptor. FO exhibited higher affinity to 5-HT 2C receptor, compared with the GABA A receptor. The oral administration of FST and FO produced a dose-dependent decrease in sleep latency and increase in sleep duration in pentobarbital-induced hypnosis. The data demonstrate that FST and FO possess sedative-hypnotic activity possibly by modulating GABA A and 5-HT 2C receptors. We propose that FST and FO might be effective agents for treatment of insomnia.

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          Antioxidant activity and γ-aminobutyric acid (GABA) content in sea tangle fermented by Lactobacillus brevis BJ20 isolated from traditional fermented foods

          Jae-Young Je, Myung-Suk Lee, Min-Ho Jeong … (2010)
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            Serotonin2C receptor localization in GABA neurons of the rat medial prefrontal cortex: implications for understanding the neurobiology of addiction.

            R. Hillman, Stephanie S. Liu, F Lanfranco … (2007)
            Serotonin (5-HT) action via the 5-HT(2C) receptor (5-HT(2C)R) provides an important modulatory influence over neurons of the prefrontal cortex (PFC), which is critically involved in disorders of executive function including substance use disorders. In the present study, we investigated the distribution of the 5-HT(2C)R in the rat prelimbic prefrontal cortex (PrL), a subregion of the medial prefrontal cortex (mPFC), using a polyclonal antibody raised against the 5-HT(2C)R. The expression of 5-HT(2C)R immunoreactivity (IR) was highest in the deep layers (layers V/VI) of the mPFC. The 5-HT(2C)R-IR was typically most intense at the periphery of cell bodies and the initial segment of cell processes. Approximately 50% of the 5-HT(2C)R-IR detected was found in glutamate decarboxylase, isoform 67 (GAD 67)-positive neurons. Of the subtypes of GABA interneurons identified by expression of several calcium-binding proteins, a significantly higher percentage of neurons expressing IR for parvalbumin also expressed 5-HT(2C)R-IR than did the percentage of neurons expressing calbindin-IR or calretinin-IR that also expressed 5-HT(2C)R-IR. Since parvalbumin is located in basket and chandelier GABA interneurons which project to cell body and initial axon segments of pyramidal cells, respectively, these results raise the possibility that the 5-HT(2C)R in the mPFC acts via the parvalbumin-positive GABAergic interneurons to regulate the output of pyramidal cells in the rat mPFC.
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              Effect of gamma-aminobutyric acid-enriched tempeh-like fermented soybean (GABA-Tempeh) on the blood pressure of spontaneously hypertensive rats.

              Kenshiro Fujimoto, Hideyuki Aoki, Yasushi Endo … (2003)
              GABA-enriched tempeh-like fermented soybean (GABA-tempeh) was supplemented to the AIN-76 diet and fed for 2 months to spontaneously hypertensive rats (SHRs), an animal model of spontaneously developed hypertension, to compare the antihypertensive activity with that of authentic GABA. The elevation of systolic blood pressure in SHRs was significantly retarded in the GABA-tempeh group as well as that with authentic GABA when compared with the controls, and the effect lasted for two months of the feeding period. The blood urea nitrogen level tended to be higher in the control group than in the GABA-supplemented groups. On the other hand, no effect was apparent on the plasma levels of cholesterol, triacylglycerol and glucose, or on the urinary excretion of Na and K.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biomol Ther (Seoul)
                Journal ID (iso-abbrev): Biomol Ther (Seoul)
                Journal ID (publisher-id): Biomol Ther (Seoul)
                Journal ID (publisher-id): ksp
                Title: Biomolecules & Therapeutics
                Publisher: The Korean Society of Applied Pharmacology
                ISSN (Print): 1976-9148
                ISSN (Electronic): 2005-4483
                Publication date (Print): September 2015
                Publication date (Electronic): 01 September 2015
                Volume: 23
                Issue: 5
                Pages: 479-485
                Affiliations
                [1 ]Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701
                [2 ]Department of Science in Korean Medicine, Graduate School, College of Korean Medicine, Kyung Hee University, Seoul 130-701
                [3 ]Marine Bioprocess Co., Ltd., Busan 619-912
                [4 ]Department of Oriental Neuropsychiatry, Kyung Hee University Korean Medicine Hospital at Gangdong, Seoul 05278
                [5 ]Department of Family Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea
                Author notes
                [* ]Corresponding Author: E-mail: ishim@ 123456khu.ac.kr , Tel: +82-2-961-0698, Fax: +82-2-963-2175
                Article
                Publisher ID: bt-23-479
                DOI: 10.4062/biomolther.2014.122
                PMC ID: 4556209
                SO-VID: 1013ca1f-a0b6-4e8a-af3b-b73acb0ba62c
                Copyright © Copyright © 2015, The Korean Society of Applied Pharmacology
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 23 October 2014
                Date revision received : 12 May 2015
                Date accepted : 03 July 2015
                Categories
                Subject: Original Article

                Keywords: fermented marine organisms,gabaa receptor,5-ht2c receptor,pentobarbital-induced sleep,sedative-hypnotic activity
                Data availability:
                Keywords: fermented marine organisms, gabaa receptor, 5-ht2c receptor, pentobarbital-induced sleep, sedative-hypnotic activity

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