基于UPLC/Q-TOF/MS和网络药理学研究甘草渣活性部位治疗溃疡性结肠炎的潜在机制

Potential mechanism of licorice residue active site for the treatment of ulcerative colitis based on UPLC/Q-TOF/MS and net pharmacology

目的利用UPLC/Q-TOF/MS和网络药理学方法研究甘草渣活性部位(GC)治疗溃疡性结肠炎(ulcerative colitis,UC)的分子机制。方法利用UPLC/Q-TOF/MS分析GC的化学成分;通过DrugBank、CTD、STITCH和SwissTarget数据库收集并预测各化学成分的靶点。通过PharmGKB、NCBI-gene、TTD、CTD和DisGeNET数据库收集与UC相关的靶点。利用Cytoscape 3.6.1构建化学成分-靶点网络;基于String数据库,构建GC治疗UC的靶点相互作用网络,进而通过MCODE聚类分析发现核心网络,利用MCC、Degree和EPC发现关键靶点。利用CTD数据库进行KEGG(KEGG pathway analysis)通路注释分析和GO(gene ontology)生物学过程富集分析。结果GC化学成分-UC靶点网络包含31种化学成分和79个靶点,关键靶点涉及丝氨酸/苏氨酸蛋白激酶1(serine/threonine protein kinase B1,PKB1/AKT1)、白介细胞素6(interleukin 6,IL6)、肿瘤坏死因子(tumor necrosis factor,TNF)、肿瘤蛋白53(tumor protein 53,TP53)、胱天蛋白酶3(caspase 3,CASP3)和信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)等。经KEGG富集筛选得到24条与UC有关的信号通路,主要涉及pathways in cancer信号通路、TNF信号通路和malaria信号通路等;经GO功能富集分析得到20个条目。结论预测了GC治疗UC的可能作用机制,为进一步寻找有效成分和作用机制奠定了基础。

Objective To study the mechanism of licorice residue active site(GC)in the treatment of ulcerative colitis(UC)by using UPLC/Q-TOF/MS and net pharmacology.Methods Chemical components of GC were analyzed by using UPLC/Q-TOF/MS.Targets of each component in GC were searched and predicted based on DrugBank,CTD,STITCH and SwissTarget databases.UC related targets were screened through PharmGKB,NCBI-gene,TTD,CTD and DisGeNET databases.The compound-target network was constructed using Cytoseape 3.6.1.A target interaction network for GC on UC was constructed based on String database,the core network was found by using MCODE cluster analysis,and the key targets were found based on using MCC,Degree and EPC.KEGG(KEGG pathway analysis)pathway annotation analysis and GO(gene ontology)biological process enrichment analysis were performed based on CTD database.Results There are 31 components and 79 targets in GC compound-target network,and the key targets include AKTI,IL6,TNF,TP53,CASP3 STAT3 and so on.KEGG pathway enrichment screening resulted in 24 associations with UC,mainly involving cancer pathway,TNF pathway and malaria pathway,and Go functional enrichment analysis yielded 20 GO terms.Conclusion The main possible mechanism of GC in treating UC was predicted,which lay a foundation for the identification of effective components and the mechanism of action.