Marine polyphenol phlorotannins promote non-rapid eye movement sleep in mice via the benzodiazepine site of the GABAA receptor
Marine polyphenol phlorotannins promote non-rapid eye movement sleep in mice via the benzodiazepine site of the GABAA receptor
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DOI：
10.1007/s00213-014-3445-1
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发表时间：
2014-07-01
影响因子：
3.4
通讯作者：
Huang, Zhi-Li
中科院分区：
文献类型：
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作者：
Cho, Suengmok;Yoon, Minseok;Huang, Zhi-Li
在精神药理学方面，研究人员一直对陆生植物多酚及其合成衍生物的催眠作用感兴趣。本研究以地西泮为对照，研究了间苯甲素及其主要成分埃克斯托诺对小鼠睡眠-觉醒的影响，通过记录脑电（EEG）来观察口服根皮单宁制剂（PRT）和埃克斯托诺对睡眠-觉醒曲线的影响，并探讨其催眠机制C57 BL/6 N小鼠的肌电图。在PRT前15 min注射GABA（A）-苯二氮卓类（BZD）受体拮抗剂氟马西尼（Flumazenil）和埃克司酮（eckstolonol），观察其催眠作用，PRT（> 250 mg/kg）可显著缩短睡眠潜伏期，增加非快速眼动睡眠（NREMS）。Eckstolonol显著降低睡眠潜伏期（> 12.5 mg/kg），增加NREMS（50 mg/kg）。PRT和埃克斯托龙醇对NREMS脑电功率密度无影响。氟马西尼预处理可完全消除PRT或埃克斯托龙醇的催眠作用。我们证明，根皮单宁通过调节GABA（A）受体的BZD位点促进NREMS。这些结果表明，根皮单宁可以潜在地用作治疗失眠的草药，并作为一个有前途的结构，开发新的镇静催眠药。
In psychopharmacology, researchers have been interested in the hypnotic effects of terrestrial plant polyphenols and their synthetic derivatives. Phlorotannins, a marine plant polyphenol, could have potential as a source of novel hypnotic drugs.The effects of phlorotannins and major phlorotannin constituent eckstolonol on sleep-wake profiles in mice were evaluated in comparison with diazepam, and their hypnotic mechanism was also investigated.The effects of phlorotannin preparation (PRT) and eckstolonol orally given on sleep-wake profiles were measured by recording electroencephalograms (EEG) and electromyograms in C57BL/6N mice. Flumazenil, a GABA(A)-benzodiazepine (BZD) receptor antagonist, was injected 15 min before PRT and eckstolonol to reveal its hypnotic mechanism.PRT administration (> 250 mg/kg) produced a significant decrease in sleep latency and an increase in the amount of non-rapid eye movement sleep (NREMS). Eckstolonol significantly decreased sleep latency (> 12.5 mg/kg) and increased the amount of NREMS (50 mg/kg). PRT and eckstolonol had no effect on EEG power density of NREMS. The hypnotic effects of PRT or eckstolonol were completely abolished by pretreatment with flumazenil.We demonstrated that phlorotannins promote NREMS by modulating the BZD site of the GABA(A) receptor. These results suggest that phlorotannins can be potentially used as an herbal medicine for insomnia and as a promising structure for developing novel sedative-hypnotics.