基于网络药理学与分子对接探讨土家药复方竹节参片对肝损伤的作用机制

Mechanism of Tujia Medicine of Fufang Panax japonicus Tablets Against Liver Injury:Based on Network Pharmacology and Molecular Docking

应用网络药理学及分子对接技术,探讨土家药复方竹节参片治疗肝损伤(Liver injury,LI)的物质基础及作用机制。从TCMSP数据库和中国知网数据库中提取复方竹节参片的化合物及靶点信息;Uniprot网站将靶点信息转换为Gene,将中药-成分-Gene信息导入Cytoscape V3.8.2获得中药-成分-Gene网络;利用OMIM、GeneCards和DrugBank网站提取“Liver injury”的疾病Gene,Excel绘制Venn图获得成分-疾病交集靶点,并构建交集靶点-成分网络图确定核心成分;利用STRING网站获得交集靶点的蛋白互作(PPI)网络及核心靶点,Matascape网站对核心靶点进行基因本体(GO)功能、京都基因和基因组数据库(KEGG)通路富集分析;用AutoDock工具进行核心成分与核心靶点的分子对接。复方竹节参片中共筛选出68种有效活性成分,治疗LI的核心成分有槲皮素、山柰酚、β-谷甾醇、木犀草素、(20S)-原人参二醇和β-胡萝卜素等;治疗LI的核心靶点15个,分别为STAT3、JUN、AKT1、TP53、TNF、MAPK1、IL6、RELA、VEGFA、MAPK8、MAPK14、PIK3CA、MYC、CTNNB1和FOS。靶点主要涉及调节与DNA结合的转录因子活性、蛋白激酶活性、细胞氧化应激及炎症反应、癌症相关蛋白的表达和血管生长等生物学过程;重要通路有乙型和丙型肝炎病毒途径、癌症及癌症中的蛋白多糖、流体剪切应力和动脉粥样硬化、糖尿病并发症中的AGE-RAGE、TNF、Toll样受体和MAPK等信号通路。分子对接结果显示,核心成分与关键靶点的结合活性良好。本研究表明,复方竹节参片可能通过作用于上述STAT3、JUN和AKT1等核心靶点,参与相关生物进程及通路的调节,进而发挥对LI的多成分-多靶点-多通路的治疗作用,本文为进一步研究复方竹节参片对LI的作用机制提供理论参考。

The material basis and possible mechanism of compound Panax japonicus tablets in the treatment of Liver injury(LI) were studied by network pharmacology and molecular docking technique.The composition and target information of compound P.japonicus tablets were extracted by TCSSP and CNKI databases.Using the Uniprot web site to convert target information into Gene.The information of herbcomposition-gene was introduced into Cytoscape V3.8.2 to obtain it's network.Using Omim,GeneCards and Druggbank to extract the disease targets of "Liver injury",Excl to draw Venn diagram to obtain the cross targets,and construct cross target-composition network to determine the core components.Use the STRING web site to obtain a cross-target protein-protein interaction(PPI) network to determine the core targets.Gene ontology(GO) function and Genome Encyclopedia(KEGG) pathway enrichment analysis of the core targets were carried out by Matascape.Molecular docking between core components and core targets using the AutoDock tool.A total of 68 active components were isolated from compound P.japonicus tablets,the core components are Quercetin,Kaempferol,β-sitosterol,Luteolin,(20S)-protopanaxadiol,Beta-carotene,and so on.The core therapeutic targets are STAT3,Jun,AKT1,TP53,TNF,MAPK1,IL6,Rela,Vegfa,Mapk8,MAPK14,PIK3CA,MYC,CTNNB1,FOS.The targets are mainly involved in the regulation of DNA-binding transcription factor activity,protein kinase activity,cell oxidative stress and inflammatory response,expression of cancer-related proteins,and vascular growth.Important pathways are the B and Hepatitis C virus pathway,proteoglycan in cancer and cancer,fluid shear stress and arteriosclerosis,AGE-RAGE signaling pathway in diabetic complications,TNF,Toll like receptors,MAPK,and so on.The results of molecular docking show that the core components have good binding activity with the key target.Compound P.japonicus tablets may play a role in the treatment of LI by acting on STAT3,JUN,AKT1 and other core targets,and participating in the regulation of related biological processes and pathways,this study laid a foundation for further study on the mechanism of compound P.japonicus tablets on LI.