Xiao Fengqin, Shao Shuai, Zhang Hongyin, Li Guangfu, Piao Songlan, Zhao Daqing, Li Guangzhe, Yan Mingming
Northeast Asia Research Institute, Changchun University of Traditional Chinese Medicine, Changchun, China.
Jilin Provincial Science and Technology Innovation Center of Health Food of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.
Front Pharmacol. 2022 Nov 22;13:965308. doi: 10.3389/fphar.2022.965308. eCollection 2022.
var. spinosa (Bunge) Hu ex H.FChow [Rhamnaceae; Ziziphi Spinosae Semen (ZSS)] has attracted extensive attention as the first choice of traditional Chinese medicine in the treatment of insomnia. However, recent studies on the sleep-improving mechanism of ZSS have mainly focused on the role of single components. Thus, to further reveal the potential mechanism of ZSS, an assessment of its multiple constituents is necessary. In this study, ZSS extract (ZSSE) was obtained from ZSS detailed modern extraction, separation, and purification technologies. The chemical constituents of ZSSE were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). For experiments, a rat model of insomnia induced by p-chlorophenylalanine (PCPA) was established to investigate the potential effect and corresponding mechanism of ZSSE on improving sleep. Hematoxylin-eosin staining (HE) results revealed that the drug group showed prominent advantages over the model group in improving sleep. Moreover, the brain levels of γ-aminobutyric acid (GABA), glutamic acid (Glu), 5-hydroxytryptamine (5-HT), and dopamine (DA) were monitored enzyme-linked immunosorbent assay (ELISA) to further study the sleep-improving mechanism of ZSSE. We found that sleep was effectively improved upregulation of GABA and 5-HT and downregulation of Glu and DA. In addition, molecular mechanisms of ZSSE in improving sleep were studied by immunohistochemical analysis. The results showed that sleep was improved by regulating the expression levels of GABA receptor subunit alpha-1 (GABARα1) and GABA acid receptor subunit gamma-2 (GABARγ2) receptors in the hypothalamus and hippocampus tissue sections. Therefore, this work not only identified the active ingredients of ZSSE but also revealed the potential pharmacological mechanism of ZSSE for improving sleep, which may greatly stimulate the prospective development and application of ZSSE.
酸枣仁变种（Bunge）胡先骕改隶于鼠李科；酸枣仁作为治疗失眠的首选中药受到广泛关注。然而，近期关于酸枣仁改善睡眠机制的研究主要集中在单一成分的作用上。因此，为进一步揭示酸枣仁的潜在机制，有必要对其多种成分进行评估。本研究采用详细的现代提取、分离和纯化技术从酸枣仁中获得酸枣仁提取物（ZSSE）。通过高效液相色谱 - 质谱联用（HPLC - MS）分析ZSSE的化学成分。为进行实验，建立了对氯苯丙氨酸（PCPA）诱导的大鼠失眠模型，以研究ZSSE改善睡眠的潜在作用及相应机制。苏木精 - 伊红染色（HE）结果显示，药物组在改善睡眠方面比模型组具有显著优势。此外，采用酶联免疫吸附测定（ELISA）监测大脑中γ - 氨基丁酸（GABA）、谷氨酸（Glu）、5 - 羟色胺（5 - HT）和多巴胺（DA）的水平，以进一步研究ZSSE改善睡眠的机制。我们发现，通过上调GABA和5 - HT以及下调Glu和DA可有效改善睡眠。此外，通过免疫组织化学分析研究了ZSSE改善睡眠的分子机制。结果表明，通过调节下丘脑和海马组织切片中GABA受体亚基α - 1（GABARα1）和GABA酸受体亚基γ - 2（GABARγ2）受体的表达水平可改善睡眠。因此，本研究不仅鉴定了ZSSE的活性成分，还揭示了ZSSE改善睡眠的潜在药理机制，这可能极大地促进ZSSE的前瞻性开发和应用。
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