基于网络药理学探讨济川煎药物君臣佐使配伍在便秘治疗中协同增效的作用机制  

To explore the synergistic mechanism of Jichuan decoction Junchen Zuoshi in the treatment of constipation based on network pharmacology

作　　者：余清华 杨亮 杨颖 袁雪金 王宇 张艺嘉 顾尽晖[5] YU Qinghua;YANG Liang;YANG Ying;YUAN Xuejin;WANG Yu;ZHANG Yijia;GU Jinhui(Suzhou High-tech Zone Hospital of Traditional Chinese Medicine,Suzhou 215000,China)

机构地区：[1]苏州高新区中医医院外科,215000 [2]贵州中医药大学第二附属医院药学部 [3]苏州市高新区人民医院康复医学科 [4]贵州中医药大学研究生院 [5]南京中医药大学附属苏州市中医医院肛肠科

出　　处：《环球中医药》2023年第5期898-913,共16页Global Traditional Chinese Medicine

基　　金：国家重点研发计划(2018YFC2002300);贵州中医药大学第二附属医院院内科研启动基金(GZZYYDXEFY-001)。

摘　　要：目的采用网络药理学和分子对接方法探讨济川煎药物君臣佐使配伍在便秘治疗中协同增效的潜在分子作用机制。方法通过TCMSP、Uniprot数据库获取济川煎组成药物的活性成分和对应靶基因;GeneCards、OMIM、TTD数据库获取便秘靶基因;Venny在线软件构建韦恩图,获取药物-疾病交集基因;STRING平台构建PPI网络,Cytoscape软件构建“药物—活性成分—靶基因”网络,并通过拓扑学分析获取潜在核心活性成分及靶基因;Metascape数据库对潜在作用靶点进行GO功能富集分析和KEGG通路富集分析;Autodock Vina和Pymol软件对关键核心靶点及其对应有效成分进行分子对接;探讨活性成分、靶基因的分布特点与君臣佐使配伍关系。结果共获得药物活性成分37个,潜在核心有效活性成分21个,其中槲皮素、β-谷固醇、山奈酚、汉黄芩素、豆甾醇为主要核心有效活性成分。药物-疾病交集靶基因182个,潜在核心靶基因37个,AKT1、TP53、TNF、IL6、JUN、VEGFA、CASP3为主要核心靶基因。GO分析获得生物进程(biological Process,BP)条目1428条、细胞组分(cellular component,CC)条目62条、分子功能(molecular function,MF)条目97条;KEGG通路富集分析获得MAPK、TNF、PI3K-Akt信号通路为主要信号通路共169条。分子对接结果均显示结合性好,构象稳定,均能形成氢键。结论济川煎可通过多成分、多靶点、多通路发挥君臣佐使协同增效作用,进而在便秘、肿瘤、心脑血管等疾病中发挥疗效。Objective Network pharmacology and molecular docking methods were used to explore the potential molecular mechanism of synergistic effects of Jichuan decoction Junchen Zuoshi in the treatment of constipation.Methods The active ingredients and corresponding target genes of Jichuan decoction were obtained by TCMSP and Uniprot database.Target genes of constipation were obtained from GeneCards,OMIM and TTD databases.Venny’s online software was used to build Venn diagrams to capture drug-disease transfer genes;PPI network was constructed on STRING platform,and Cytoscape software was used to construct a“drug-activity-target gene”network,and the potential core active ingredients and target genes were obtained through topology analysis.Metascape database was used for GO function enrichment analysis and KEGG pathway enrichment analysis of potential targets.Autodock Vina and Pymol software were used for molecular docking of key core targets and their corresponding active components.To explore the distribution characteristics of active ingredients,target genes and the compatibility of Junchen Zuoshi.Results A total of 37 active ingredients and 21 potential core active ingredients were obtained,β-sitosterol,kaempferol,hanbaicalein and stigmasterol were the main core active ingredients among them.There were 182 target genes of drug-disease intersection,and 37 potential core target genes,including AKT1,TP53,TNF,IL6,JUN,VEGFA and CASP3.1428 Biological Process(BP)items,62 Cellular Component(CC)items and 97 molecular function(MF)items were obtained by GO analysis.A total of 169 signaling pathways about MAPK,TNF and PI3K-Akt were identified by KEGG pathway enrichment analysis.The results of molecular docking show that the bond was good,conformation was stable,and hydrogen bond could be formed.Conclusion Jichuan decoction can exert synergistic effects of Junchen Zuoshi through multiple components,multiple targets and multiple pathways,and thus play an effective role in constipation,tumor,cardiovascular and cerebrovascular di

关 键 词：济川煎 便秘 网络药理学 分子对接 君臣佐使 作用机制 

分 类 号：R256.35[医药卫生—中医内科学]