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[摘要]
目的 基于分子网络研究四逆散治疗抑郁症的潜在生物学机制。方法 借助于中药系统药理学数据库和分析平台(TCMSP)数据库筛选四逆散的活性成分,筛选条件为口服利用率、药物相似性和血脑屏障透过率,并挖掘四逆散活性成分靶点和抑郁症的治疗靶点。利用韦恩图找到活性成分靶点和疾病靶点的交集靶点,对应相应成分定义为四逆散抗抑郁的有效成分。利用String在线数据库进行交集靶点蛋白质-蛋白质相互作用网络的预测,并利用DAVID数据库进行交集靶点KEGG信号通路的富集分析。最后使用Cytoscape 3.6软件进行活性成分-靶点网络及有效成分-靶点-信号通路的构建和拓扑分析。结果 筛选出了四逆散107个有效成分和28个重要的抗抑郁症靶点。四逆散抗抑郁症的重要靶点显著富集于神经活性配体-受体相互作用、5-羟色胺能突触、多巴胺能突触、逆行内源性大麻素信号传导、钙信号通路等10个信号通路中。结论 本研究从分子网络的角度初步揭示了四逆散治疗抑郁症的潜在作用机制,其主要的生物学机制可能与以神经活性配体-受体相互作用为中心的信号通路有关。
[Key word]
[Abstract]
Objective Based on molecular network, the underlying biological mechanism of Sini Powder in the treatment of depression was studied. Methods Using TCMSP database to screen the active components of Sini Powder, the screening conditions were oral utilization, drug similarity and blood-brain barrier permeability, and the therapeutic targets of Sini Powder and depression were found. The intersections of active component targets and disease targets were found by using Venn diagram, and the corresponding components were defined as effective components of tetrastigmatic anti-depression. A string online database was used to predict the intersecting target protein-protein interaction network, and a DAVID database was used to conduct the enrichment analysis of the KEGG signal pathway of the intersecting target. Finally, Cytoscape 3.6 was used to construct the active componenttarget network and active component-target-signal pathway. Results We screened out 107 active ingredients and 28 important antidepression targets. Antidepressant when one of the important targets significantly enriched in Neuroactive ligand-receptor interaction and Serotonergic synapse, Dopaminergic synapse, Retrograde endocannabinoid signaling, Calcium signaling pathway, etc. 10 in the signal path. Conclusion This study preliminarily revealed the potential mechanism of the therapeutic effect of Sini Powder on depression from the perspective of molecular network, and its main biological mechanism may be related to the signaling pathway centered on the Neuroactive ligand-receptor interaction.
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[基金项目]
国家自然科学基金重点项目(81430102)