基于网络药理学和分子对接法探讨参苓白术散治疗肺癌分子机制

Molecular Mechanism of Shenling Baizhu Powder(参苓白术散)in the Treatment of Lung Cancer Based on Internet Pharmacology

目的通过网络药理学和分子对接法,探索培土生金法代表方剂参苓白术散辅助治疗肺癌的潜在作用机制。方法通过TCMSP、SymMap、ETCM数据库检索并收集参苓白术散的活性成分,借助TCMSP、TCMID、TargetNet、SymMap和Uniprot数据库筛选药物成分的作用靶点,借助GeneCards、OMIM、PharmGkb、TTD和Drugbank共5个疾病在线数据库,以“lung cancer”为关键词搜索疾病相关靶点,把药物成分作用靶点与疾病靶点作交集得到参苓白术散作用于肺癌的预测靶点。采用Cytoscape 3.7.2软件构建“药物-活性成分-靶点网络”图。利用String数据库获取蛋白互作信息,进一步通过MCODE插件对靶点网络进行模块分析,筛选核心作用靶点。运用Metascape平台将核心靶点进行KEGG通路富集分析,并根据富集结果,运用Cytoscape 3.7.2软件将与免疫系统显著关联的信号通路以及映射在通路中的靶点基因与相关药物成分整合绘制“药物-成分-基因-通路”图,从整体生物网络角度阐述参苓白术散治疗肺癌的免疫炎症机制,最后加以分子对接验证。结果筛选得到参苓白术散938个活性成分,与疾病交集靶点610个。KEGG富集分析表明核心靶点作用于IL-17 signaling pathway、Toll-like receptor signaling pathway、NOD-like receptor signaling pathway及Chemokine signaling pathway等多种免疫和炎症相关的信号通路,分子对接显示核心化合物与靶点具有良好的对接活性。结论通过网络药理学的初步筛选与预测,参苓白术散治疗肺癌涉及多靶点、多通路作用机制,其有效成分可能通过调控免疫和炎症信号通路而达到辅助治疗癌症目的,可为后续的深入研究提供方向。

Objective To explore the potential mechanism of Shenling Baizhu Powder(参苓白术散),a representative prescription of reinforcing earth to generate gold,treating lung cancer through network pharmacology and Docking.Methods The active components of Shenling Baizhu Powder were searched and collected by the databases of TCMSP,SymMap,and ETCM,and the active targets of drug components were screened by the databases of TCMSP,TCMID,TargetNet,SymMap,and Uniprot Using GeneCards,OMIM,PharmGkb,TTD and drug bank five disease online databases,“lung cancer”was used to search for disease-related targets.The targets of drug components and disease were crossed to get the predictive targets of Shenling Baizhu Powder on lung cancer.The drug-active ingredient-target network was constructed by Cytoscape 3.7.2 software.The protein-protein interaction information was obtained from the String database,and the target network was analyzed by MCODE plug-in to screen the core action targets.Using Metascape platform to enrich the KEGG pathway at the core target,and based on the enrichment results,using Cytoscape3.7.2 software,the“drug-component-gene-pathway”map was constructed by integrating the immune system-associated signaling pathways and the target genes mapped in the pathways with the related drug components,the immunoinflammatory mechanism of Shenling Baizhu Powder in the treatment of lung cancer was expounded from the angle of a whole biological network.Results 938 active components of Shenling Baizhu Powder were obtained,and 610 were cross-targeted with the disease.KEGG enrichment analysis showed that the core targets acted on many signaling pathways,such as the IL-17 signaling pathway,Toll-like signaling pathway,NOD-like signaling pathway,and Chemokine signaling pathway.Conclusion Through the preliminary screening and prediction of network pharmacology,Shenling Baizhu Powder in the treatment of lung cancer involves a multi-target,multi-channel mechanism of action,and its effective components may achieve the goal of adjuvant treatment of cancer by affecting the inflammatory signal pathway,it can provide the direction for further study.