[关键词]
[摘要]
目的 采用网络药理学的方法,研究逍遥散与开心散的活性成分、作用靶点及生物学意义,探讨其“同病异治”抑郁症的作用机制。方法 采用TCMID、Batman-TCM、TCM database@Taiwan分别获取逍遥散和开心散的成分和靶点,通过TTD、PharmGkb、CTD、Genecard、OMIM、DrugBank筛选抑郁症相关的蛋白,构建蛋白相互作用网络(PPI),通过Cytoscape的Network Analyzer工具进行靶点的拓扑属性分析,运用其插件ClusterViz的MCODE算法进行聚类分析,DAVID通路进行生物过程和通路富集分析。结果 网络分析结果表明两方可能通过INS、AKT1、TP53、IL6、CREB1等关键蛋白,神经活性配体-受体相互作用、cAMP信号通路、5-羟色胺能神经突触、Calcium信号通路和胆碱能突触发挥抗抑郁的作用。PIK3CA、BDNF、PIK3R1、NGF蛋白所在的PI3K-Akt、钙离子等信号通路为逍遥散特有的抗抑郁机制;CCND1、PRKACA、GCLM、GCLC蛋白所在的Oxytocin信号通路、胆碱能突触等通路为开心散特有的抗抑郁机制。结论 逍遥散和开心散由于组方差异,在抗抑郁靶点方面既有相同也有不同;通过对靶点和通路的分析初步阐明抑郁症“同病异治”的科学内涵。
[Key word]
[Abstract]
Objective The network pharmacology method was used to predict the active components, targets, and mechanism of Xiaoyao Powder and Kaixin Powder, and to explore the molecular mechanism of depression "same disease with different treatments". Methods TCMID, Batman-TCM, and TCM database@Taiwan were used to predict the targets and ingredients of Xiaoyao Powder and Kaixin Powder. The prediction was made via screening out the antidepressive drug targets approved by TTD, PharmGkb, CTD, Genecard, OMIM, DrugBank database, and constructing protein interaction network (PPI). Through the Network Analyzer tool of Cytoscape, the topology of the target was analyzed, the MCODE algorithm of the plug-in ClusterViz was used for cluster analysis, and the DAVID biological molecular function software was used to perform enrichment analysis. Results The network analysis indicated that two prescriptions may play antidepressant roles through INS, AKT1, TP53, IL6, and CREB1 targets, involving neuroactive ligand-receptor interaction, cAMP signaling pathway, serotonergic synapse, calcium signaling pathway, and cholinergic synapse pathways. The unique antidepressant mechanism for Xiaoyao Powder is that PIK3CA, BDNF, PIK3R1, and NGF target the PI3K-Akt, calcium, and other signal pathways, and CCND1, PRKACA, GCLM, GCLC targeting oxytocin signaling pathway, cholinergic synapses, and other pathways is considered as Kaixin Powder unique antidepressive mechanism. Conclusion Xiaoyao Powder and Kaixin Powder have similarities and differences in antidepressant targets due to their differences in composition, and the scientific connotation of "same disease with different treatments" is preliminarily clarified by the analysis of the target and the pathway.
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[基金项目]
国家“重大新药创制”科技重大专项(2017ZX09301047);中国博士后科学基金面上资助项目(2016M602414);山西省科技重点研发计划项目(201603D3113013,201603D321077);山西省自然科学基金项目(201701D22111344);山西省重点实验室资助项目(201605D111004);山西省科技创新重点团队资助项目(201605D131045-18);山西省研究生教育创新项目(2016SY007,2017JD02)