Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, induces sleep via the benzodiazepine site of GABAA receptor in mice
Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, induces sleep via the benzodiazepine site of GABAA receptor in mice
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厚朴酚是厚朴树皮的主要生物活性成分，通过 GABAA 受体的苯二氮卓位点诱导小鼠睡眠。
DOI：
10.1016/j.neuropharm.2012.06.031
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发表时间：
2012-11-01
影响因子：
4.7
通讯作者：
Qu, Wei-Min
中科院分区：
文献类型：
--
作者：
Chen, Chang-Rui;Zhou, Xu-Zhao;Qu, Wei-Min
厚朴酚（6,6',7,12-四甲基氧基-2.2'-二甲基-1- β -小檗碱，C18H18O2）是厚朴树皮的一种有效成分，据报道，厚朴酚通过GABA(A)受体发挥有效的抗癫痫作用。这种受体还能调节人类和动物的睡眠。本研究通过记录小鼠脑电图和肌电图，探讨厚朴酚对睡眠行为的调节作用。结果表明，厚朴酚5或25 mg/kg给药后3 h内可显著缩短睡眠潜伏期，增加非快速眼动（non-REM， NREM）和快速眼动（REM）睡眠时间，增加NREM和REM睡眠发作次数。厚朴酚5和25 mg/kg剂量增加了清醒次数，但减少了清醒持续时间。另一方面，厚朴酚增加了从清醒到非快速眼动睡眠以及随后从非快速眼动睡眠到清醒的状态转换次数。免疫组化研究显示，厚木酚增加了下丘脑前部睡眠中枢腹外侧视前区神经元c-Fos的表达，降低了下丘脑尾侧唤醒结节-乳头核中c-Fos的表达。厚朴酚诱导的睡眠促进作用和c-Fos的变化被氟马西尼逆转，氟马西尼是GABA(A)受体苯二氮平部位的拮抗剂。这些结果表明厚朴酚通过GABA(A)受体增加NREM和REM睡眠。(C) 2012 Elsevier Ltd.版权所有。
Magnolol (6,6',7,12-tetramethoxy-2.2'-dimethyl-1-beta-berbaman, C18H18O2), an active ingredient of the bark of Magnolia officinalis, has been reported to exert potent anti-epileptic effects via the GABA(A) receptor. The receptor also mediates sleep in humans and animals. The aim of this study was to determine whether magnolol could modulate sleep behaviors by recording EEG and electromyogram in mice. The results showed that magnolol administered i.p. at a dose of 5 or 25 mg/kg could significantly shorten the sleep latency, increase the amount of non-rapid eye movement (non-REM, NREM) and rapid eye movement (REM) sleep for 3 h after administration with an increase in the number of NREM and REM sleep episodes. Magnolol at doses of 5 and 25 mg/kg increased the number of bouts of wakefulness but decreased their duration. On the other hand, magnolol increased the number of state transitions from wakefulness to NREM sleep and subsequently from NREM sleep to wakefulness. Immunohistochemical study showed that magnolol increased c-Fos expression in the neurons of ventrolateral preoptic area, a sleep center in the anterior hypothalamus, and decreased c-Fos expression in the arousal tuber-omammillary nucleus, which was located in the caudolateral hypothalamus. The sleep-promoting effects and changes in c-Fos induced by magnolol were reversed by flumazenil, an antagonist at the benzodiazepine site of the GABA(A) receptor. These results indicate that magnolol increased NREM and REM sleep via the GABA(A) receptor. (C) 2012 Elsevier Ltd. All rights reserved.