基于网络药理学探讨苦参治疗骨癌痛的分子机制

Discussion of Molecular Mechanism of Sophora Flavescens in Treatment of Cancer-Induced Bone Pain by Network Pharmacology

目的:运用网络药理学的方法探讨苦参治疗骨癌痛的潜在机制。方法:从中药系统药理学数据库与分析平台(TCMSP)和中药分子机制生物信息学分析工具(BATMAN-TCM)数据库中获取苦参的成分,然后利用TCMSP数据库对活性成分进行药代动力学分析,筛选出其中符合要求的活性化合物,再通过靶点预测数据库(Swiss)预测苦参中活性化合物的靶标。此外,利用对比毒理基因组学数据库(CTD)进行基因本体论(GO)和京都基因组百科全书(KEGG)信号通路富集分析。最后,利用Cytoscape软件构建"苦参-化合物-靶标-疾病"网络。结果:符合TCMSP数据库中药代动力学筛选条件,且能以其化合物3D分子结构反向预测靶点的活性成分共有34个。STRING数据库筛选出32个网络核心靶点。对24个候选靶点进行GO富集分析发现,核心靶基因主要参与调节神经再生、炎症反应、神经分化、调节化学突触传递、疼痛感受、神经炎症反应等生物学过程。结论:药代动力学与网络药理学结合研究显示,苦参有34种活性成分,其中与骨癌痛密切相关的32个靶标,可通过参与多种生物过程对骨癌痛发挥治疗作用。

Objective:To explore the potential mechanism of sophora flavescens(SF)in the treatment of cancer-induced bone pain(CIBP)using network pharmacology method.Methods:The compounds in SF were collected from the TCMSP and the BATMAN-TCM databases.Pharmacokinetics analysis was performed to screen the active compounds of SF using the TCMSP database.The putative targets of active compounds in SF were predicted by Swiss database.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment were performed by the CTD database.Finally,Cytoscape software was used to construct the " SF-compound-target-disease" network.Results:A total of 34 active ingredients were in line with the TCMSP database for pharmacokinetic screening,which could reversely predict the target based on the 3 D molecular structure of their compounds.There were 32 network core targets screened out by STRING database.GO enrichment analysis of 24 candidate targets indicated that core target genes were mainly involved in regulating nerve regeneration,inflammatory response, nerve differentiation, chemical synaptic transmission,pain perception,neuroinflammatory response and other biological processes.Conclusion:The results of pharmacokinetics study combined with network pharmacology suggests SF has 34 active components and 32 targets closely related to CIBP,which can play a therapeutic role in CIBP by participating in a variety of biological processes.