Joung Hye-Young, Kang Young Mi, Lee Bae-Jin, Chung Sun Yong, Kim Kyung-Soo, Shim Insop
Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701 ; Department of Science in Korean Medicine, Graduate School, College of Korean Medicine, Kyung Hee University, Seoul 130-701.
Marine Bioprocess Co., Ltd., Busan 619-912.
Biomol Ther (Seoul). 2015 Sep;23(5):479-85. doi: 10.4062/biomolther.2014.122. Epub 2015 Sep 1.
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 GABAA-benzodiazepine and 5-HT2C 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 GABAA and 5-HT2C receptor binding assays, FST displayed an effective concentration-dependent binding affinity to GABAA receptor, similar to the binding affinity to 5-HT2C receptor. FO exhibited higher affinity to 5-HT2C receptor, compared with the GABAA 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 GABAA and 5-HT2C receptors. We propose that FST and FO might be effective agents for treatment of insomnia.
本研究旨在调查由短乳杆菌BJ20(L. brevis BJ20)发酵富含γ-氨基丁酸(GABA)的海洋生物(FMO)(包括海带(FST)和牡蛎(FO))的镇静催眠活性。对FST和FO进行了GABAA-苯二氮卓和5-HT2C受体的结合活性测试,这两种受体是众所周知的助眠分子靶点。我们还测量了小鼠口服FST和FO后在戊巴比妥诱导睡眠期间的睡眠潜伏期和睡眠时间。在GABAA和5-HT2C受体结合试验中,FST对GABAA受体表现出有效的浓度依赖性结合亲和力,类似于对5-HT2C受体的结合亲和力。与GABAA受体相比,FO对5-HT2C受体表现出更高的亲和力。在戊巴比妥诱导的催眠状态下,口服FST和FO可使睡眠潜伏期呈剂量依赖性缩短,睡眠时间延长。数据表明,FST和FO可能通过调节GABAA和5-HT2C受体而具有镇静催眠活性。我们认为FST和FO可能是治疗失眠的有效药物。