Wang Tian-Xiao, Wei Hao-Hua, Chen Ze-Ka, Qu Wei-Min, Huang Zhi-Li
Department of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, and Institutes of Brain Science, Fudan University, Shanghai, China.
Department of Human Anatomy & Histoembryology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Sleep Breath. 2021 Sep;25(3):1613-1623. doi: 10.1007/s11325-020-02244-5. Epub 2020 Nov 16.
Zao Ren An Shen capsule (ZRASC) which is composed of three kinds of traditional Chinese herbs is a popular Chinese medicine for the treatment of insomnia. This study investigated the hypnotic effect of ZRASC in an anxiety-like mouse model.
We determined the role of ZRASC in anxiety and co-morbid insomnia using electroencephalogram and electromyogram recordings. Anxiety-like behaviors were tested by using the open-field, light/dark box, or elevated plus-maze in mice. Immunohistochemical techniques were employed to reveal the mechanism by which ZRASC regulated anxiety and insomnia.
ZRASC at 680 mg/kg prolonged the time spent in the central area, open arms area, and light box by 1.9, 2.3, and 1.7-fold respectively, compared with the vehicle control group in immobilization stress (IMS) mice. ZRASC at 680 mg/kg given at 08:00 h increased the amount of non-rapid eye movement sleep by 1.4-fold in a 2-h period after dosing in IMS mice. However, it did not alter the sleep-wake behaviors in normal mice. Immunohistochemistry showed that IMS increased c-Fos expression in the neurons of the stria terminalis and tuberomammillary nucleus by 1.8 and 1.6-fold, respectively. In addition, ZRASC (680 mg/kg) reversed the IMS-induced c-Fos expression.
Our results suggest that ZRASC is an effective therapeutic strategy for both anxiety disorder and sleep disturbances in an anxiety-like mouse model.
枣仁安神胶囊(ZRASC)由三种中药组成,是一种治疗失眠的常用中药。本研究在焦虑样小鼠模型中研究了ZRASC的催眠作用。
我们使用脑电图和肌电图记录来确定ZRASC在焦虑和共病失眠中的作用。通过旷场实验、明暗箱实验或高架十字迷宫实验检测小鼠的焦虑样行为。采用免疫组织化学技术揭示ZRASC调节焦虑和失眠的机制。
与固定应激(IMS)小鼠的溶剂对照组相比,680mg/kg的ZRASC分别使小鼠在中央区域、开放臂区域和明箱中的停留时间延长了1.9倍、2.3倍和1.7倍。在08:00给予680mg/kg的ZRASC可使IMS小鼠给药后2小时内的非快速眼动睡眠时间增加1.4倍。然而,它并没有改变正常小鼠的睡眠-觉醒行为。免疫组织化学显示,IMS使终纹床核和结节乳头核神经元中的c-Fos表达分别增加了1.8倍和1.6倍。此外,ZRASC(680mg/kg)逆转了IMS诱导的c-Fos表达。
我们的结果表明,在焦虑样小鼠模型中,ZRASC是治疗焦虑症和睡眠障碍的有效策略。