School of Chinese Materia Medica, Shanxi University of Chinese Medicine, Daxue Street, No.121, Jinzhong, Shanxi, China.
BMC Complement Med Ther. 2020 Jul 2;20(1):206. doi: 10.1186/s12906-020-03000-8.
Semen Ziziphi spinosae and Radix Polygalae, two herbs commonly used together in Traditional Chinese Medicine for the treatment of insomnia and anxiety. The study aims to study the sedative-hypnotic effect of the active components of the herbal pair, the possible mechanisms of such effect, and related metabolic pathways in vivo.
The sedative and hypnotic effect of the active components (EI30) of the herbal pair was studied by recording influence on the proportion of sleeping within 30 min, sleep latency and sleep length of pentobarbital sodium-induced sleeping on mice. Possible mechanisms of the sedative-hypnotic effect of the active components were investigated by measuring the content of neurotransmitters in the total protein of mice brain tissue. The main chemical compounds of the herbal pair were identified by Liquid Chromatography-Mass Spectrometry (LC-MS). Serum samples of mice were studied, and related differential metabolites between the normal group and model group, and between model group and treatment group were identified by Gas Chromatography Time-Of-Flight Mass Spectrometry (GC-TOF-MS), Principal Components Analysis (PCA), and Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA).
Compared with the control group, high dose EI30 group and the Clonazepam group were with significantly higher proportions of sleep within 30 min (P = 0.027 and 0.005 respectively). Compared with the control group, all of the high, medium and low dose of EI30 groups were with significantly shorter sleep latency (P < 0.01) and prolonged sleeping time (P < 0.01). The herbal pair has good sedative-hypnotic effects, although it is weaker than the effect of Clonazepam. The sedative-hypnotic effect of EI30 is possibly related to the adjustment of neurotransmitters 5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA) in the total protein of mice brain tissue. There are five metabolic pathways in vivo most related to the sedative-hypnotic effect of EI30, and they are biosynthesis of valine, leucine, and isoleucine, metabolism of glyceride, metabolism of alanine, aspartic acid and glutamic acid, metabolism of phenylalanine, and metabolism of cysteine and methionine.
This study reveals the mechanisms of sedative and hypnotic effects of herbal pair Semen Ziziphi spinosae and Radix Polygalae by using metabolomics methods. This study provides a basis for further development and utilization of this herbal pair.
酸枣仁与远志是两种常用的中药，用于治疗失眠和焦虑。本研究旨在研究草药对的活性成分的镇静催眠作用、其可能的作用机制以及体内相关代谢途径。
通过记录对戊巴比妥钠诱导的睡眠内 30 分钟内睡眠比例、睡眠潜伏期和睡眠时间的影响，研究草药对的活性成分（EI30）的镇静和催眠作用。通过测量小鼠脑组织总蛋白中的神经递质含量，研究活性成分的镇静催眠作用的可能机制。采用液相色谱-质谱联用（LC-MS）鉴定草药对的主要化学化合物。通过气相色谱飞行时间质谱（GC-TOF-MS）、主成分分析（PCA）和正交投影判别分析（OPLS-DA），对正常组和模型组、模型组和治疗组之间的血清样本进行研究，鉴定出差异代谢物。
与对照组相比，高剂量 EI30 组和氯硝西泮组在 30 分钟内的睡眠时间比例显著更高（P=0.027 和 0.005）。与对照组相比，高、中、低剂量 EI30 组的睡眠潜伏期均显著缩短（P<0.01），睡眠时间延长（P<0.01）。该草药对具有良好的镇静催眠作用，尽管其作用弱于氯硝西泮。EI30 的镇静催眠作用可能与调节小鼠脑组织总蛋白中的神经递质 5-羟色胺（5-HT）、去甲肾上腺素（NE）和多巴胺（DA）有关。体内与 EI30 的镇静催眠作用最相关的有五条代谢途径，它们是缬氨酸、亮氨酸和异亮氨酸的生物合成、甘油酯代谢、丙氨酸、天冬氨酸和谷氨酸代谢、苯丙氨酸代谢和半胱氨酸和蛋氨酸代谢。
本研究采用代谢组学方法揭示了酸枣仁与远志草药对的镇静催眠作用机制，为进一步开发和利用该草药对提供了依据。
