基于网络药理学探讨百合知母汤抗焦虑与失眠的分子机制

Molecular Mechanism of Baihe Zhimu Tang against Anxiety and Insomnia Based on Network Pharmacology

目的:应用网络药理学方法探讨百合知母汤抗焦虑与失眠的分子机制。方法:基于中医药整合药理学研究平台(integrative pharmacology-based research platform of traditional Chinese medicine,TCMIP)V2.0对百合知母汤化学成分信息进行靶标预测,将焦虑与失眠相关疾病靶标信息进行蛋白-蛋白互作网络(protein-protein interactions,PPI)构建;富集分析百合知母汤干预焦虑、失眠的关键靶标;构建可视化的“中药方剂-中药材-化学成分-核心靶标-关键通路-疾病关键病理环节”多层次网络关联图。结果:百合知母汤有效成分主要为皂苷、黄酮、挥发油、有机酸等,百合知母汤作用潜在靶标共128个,其中与药物相关靶标14个,与疾病相关靶标114个,药物与疾病共有靶标2个,分别为NR3C1和GABRA1。百合知母汤抗焦虑与失眠主要作用于GABRA1、NFKB1、AR、SMC1A、PIK3CA、NR3C1、DRD2等基因或蛋白靶标中,涉及氨基丁酸、氯离子跨膜运输、突触后膜电位、γ-氨基丁酸的突触传递、神经元凋亡过程负调控及信号转导效应等通路。结论:百合知母汤抗焦虑与失眠的分子作用机制可能与干预GABRA1、NFKB1、DRD2等基因或蛋白表达,调控氨基丁酸、氯离子跨膜运输等通路有关。

Objective:To explore the molecular mechanism of Baihe Zhimu Tang against anxiety and insomnia based on network pharmacology.Methods:The targets of chemical information of Baihe Zhimu Tang were predicted,PPI network was constructed with the information of anxiety-and insomnia-related disease targets via TCMIP V2.0,the key targets of herbal prescriptions in the intervention on disease were enriched to construct visualized multi-level network diagram of"Chinese medicine prescription-materia medica-chemical ingredientscore targets-key pathway-key pathological links of disesse".Results:The active ingredients of Baihe Zhimu Tang mainly contained saponins,flavonoids,volatile oils and organic acids,there were 128 potential targets related to the decoction,among which,14 medicine-related targets and 114 disease-related targets were gained,and two disease-medicine shared targets including NR3C1 and GABRA1 respectively.Baihe Zhimu Tang could treat anxiety and insomnia mainly by acting on the genes or the targets of protein such as GABRA1,NFKB1,AR,SMC1A,P1K3CA,NR3C1 and DRD2,involving aminobutyric acid signalling pathway,chloride transmembrane transport,postsynaptic membrane potential,synaptic transmission of γ-aminobutyric acid,negative regulation of neuronal apoptotic processes and signal transduction effect.Conclusion:Molecular mechanism of Baihe Zhimu Tang in the treatment of anxiety and insomnia might be related to the intervention on the expressions of GABRA1,NFKB1 and DRD2 gene or protein,regulating aminobutyric acid signalling pathway and chloride transmembrane transport.