Yuan Zhao, Hong-Xia Zheng, Ying X U, Na Lin
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital Shenzhen 518033, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2020 Sep;45(17):4129-4139. doi: 10.19540/j.cnki.cjcmm.20200622.401.
This paper aims to explore the potential of Qingyan Formula(QYF) in the treatment of perimenopausal anxiety disorder(PAD) by network pharmacological method, and verify the pharmacodynamics and mechanism by using animal experiments. First, Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP) was used to retrieve the active components of QYF. Then the potential drug targets were screened with use of Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine(TCMIP) v2.0 and Swiss Target Prediction database. Targets related to PAD were retrieved and screened from the OMIM database and GeneCards database. The intersection targets of QYF and PAD were screened out, and then the enrichment analysis of the signal pathways was conducted. Open field experiments and the O maze experiment were used to verify the pharmacodynamic effect of QYF in the treatment of PAD rats, and the serum neurotransmitter level was detected. The results showed that QYF may be have the function of regulating steroid hormone signaling pathways such as steroid hormone synthesis, ovarian steroidogenesis and estrogen signaling pathways, regulating central neurotransmitters signaling pathways including tryptophan metabolism pathways, Toll-like receptor signaling pathways, TGF-β signaling pathway and regulating inflammatory response pathways including NF-κB signaling pathway, Apelin signaling pathway, MAPK signaling pathway, TNF signaling pathway, and FOXO signaling pathway. All of the signaling pathways were related to PAD, which indicated that QYF may have the role of treating PAD. Qingyan Formula 70% ethanol extract(QYFE) revealed anxiolytic effects by extending the activity time and distance of anxious ovariectomized(OVX) rats in the central field of open field experiments, and increasing the duration and activity distance of anxious OVX rats in the open arm area in O maze experiments. QYFE increased serum serotonin/5-hydroxytryptamine(5-HT), and gamma aminobutyric acid(GABA) levels in anxious OVX rats, significantly reduced glutamate(Glu) and norepinephrine(NA) levels, and reversed the disturbance of excitatory/suppressive transmitter balance caused by OVX, which may be related to its effect on alleviating anxiety disorder in OVX rats.
本文旨在通过网络药理学方法探讨清咽方（QYF）治疗围绝经期焦虑症（PAD）的潜力，并通过动物实验验证其药效学及作用机制。首先，利用中药系统药理学数据库与分析平台（TCMSP）检索清咽方的活性成分。然后，使用基于整合药理学的中药网络计算研究平台（TCMIP）v2.0和瑞士靶点预测数据库筛选潜在药物靶点。从OMIM数据库和基因卡片数据库检索并筛选与PAD相关的靶点。筛选出清咽方与PAD的交集靶点，随后进行信号通路富集分析。采用旷场实验和O迷宫实验验证清咽方治疗PAD大鼠的药效学作用，并检测血清神经递质水平。结果表明，清咽方可能具有调节类固醇激素合成、卵巢类固醇生成和雌激素信号通路等类固醇激素信号通路，调节色氨酸代谢通路、Toll样受体信号通路、TGF-β信号通路等中枢神经递质信号通路，以及调节NF-κB信号通路、Apelin信号通路、MAPK信号通路、TNF信号通路和FOXO信号通路等炎症反应通路的功能。所有这些信号通路均与PAD相关，这表明清咽方可能具有治疗PAD的作用。清咽方70%乙醇提取物（QYFE）通过延长去卵巢（OVX）焦虑大鼠在旷场实验中央区域的活动时间和距离，以及增加OVX焦虑大鼠在O迷宫实验开放臂区域的停留时间和活动距离，显示出抗焦虑作用。QYFE提高了OVX焦虑大鼠血清5-羟色胺（5-HT）和γ-氨基丁酸（GABA）水平，显著降低了谷氨酸（Glu）和去甲肾上腺素（NA）水平，并逆转了OVX引起的兴奋性/抑制性递质平衡紊乱，这可能与其减轻OVX大鼠焦虑症的作用有关。
