基于网络药理及分子对接探讨茵陈五苓散治疗原发性胆汁性胆管炎的作用机制

The Mechanism of Yinchen Wuling Powder on Primary Biliary Cholangitis Based on Network Pharmacology and Molecular Docking

目的:基于网络药理学及分子对接技术探讨茵陈五苓散治疗原发性胆汁性胆管炎(PBC)的潜在作用机制。方法:运用系统药理学数据库和分析平台(TCMSP)检索茵陈五苓散的活性成分和作用靶点。通过GeneCard、OMIM数据库收集疾病靶点。运用Cytoscape3.7.2软件构建化合物-靶点网络。采用R语言进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。将药理网络中的核心活性化合物与法尼醇X受体(FXR)进行分子对接,同时比较推荐的化学药物与FXR的结合活性。结果:化合物-靶点网络筛选出茵陈五苓散核心活性化合物为槲皮素、异鼠李素、β-谷甾醇、阿特匹林A、猪毛蒿、芫花黄素、茵陈黄酮、3β-乙酞氧基苍术酮、二氢槲皮素、去甲氧基茵陈色原酮等。得到GO条目2189条(P<0.05),KEGG通路富集分析得到155条信号通路(P<0.05)。分子对接结果显示核心活性化合物与FXR亲和力与推荐药物相近。结论:茵陈五苓散对PBC的干预作用的潜在机制可能是槲皮素、异鼠李素、β-谷甾醇、阿特匹林A、猪毛蒿、芫花黄素、茵陈黄酮、3β-乙酞氧基苍术酮、二氢槲皮素、去甲氧基茵陈色原酮等活性化合物通过与FXR结合作用于AKT1、JUN、MAPK1、RELA、IL6、MAPK14、EGFR、ESR1、FOS、CCND1等靶点调节多条信号通路而发挥作用。

Objective:To explore the potential mechanism of intervention effect of Yinchen Wuling Powder on primary biliary cholangitis(PBC)based on network pharmacology and molecular docking.Methods:The chemical composition and target of Yinchen Wuling Powder were retrieved by traditional Chinese medicine systems pharmacology(TCMSP).Disease targets were collected by GeneCard and OMIM databases.Cytoscape3.7.2 software was used to construct the compound-target network of medicinal materials.Gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were carried out by R language.The core active compound in the pharmacological network is molecularly docked with the farnesoid X receptor(FXR),and the binding activity of recommended chemical drugs and FXR were compared.Results:The compound-target network screened out the core active compounds of Yinchen Wulingsan as quercetin,isorhamnetin,β-sitosterol,atropirin A,Artemisia serrata,Daphne flavonoids,flavonoids,3β-Beta Phthalooxy atractylone,dihydroquercetin,demethoxy chromogenone,etc.2189 GO entries were obtained(P<0.05),and KEGG pathway enrichment analysis yielded 155 signal pathways(P<0.05).The molecular docking results showed that the affinity of the core active compound and FXR was similar to the recommended drug.Conclusion:The potential mechanism of Yinchen Wuling Powder′s intervention on PBC may be quercetin,isorhamnetin,β-sitosterol,atropyrin A,Artemisia halodendron,Daphne flavonoid,Yinchen flavone,3β-ethylphthalide active compounds such as oxyatractone,dihydroquercetin,and demethoxyl chromogenone can act on AKT1,JUN,MAPK1,RELA,IL6,MAPK14,EGFR,ESR1,FOS,CCND1 and other targets by binding to FXR point adjusts multiple signal pathways to play a role.