戚璐 徐俊 许杰 楼汪洲洋 程良斌

摘要 目的：基于網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2 189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。

关键词 网络药理学;分子对接;茵陈五苓散;原发性胆汁性胆管炎;原发性胆汁性肝硬化

The Mechanism of Yinchen Wuling Powder on Primary Biliary Cholangitis Based

on Network Pharmacology and Molecular Docking

QI Lu1，XU Jun1，XU Jie1，LOU Wangzouyang1，CHENG Liangbin1，2

（1 Clinical College of Traditional Chinese Medicine，Hubei University of Chinese Medicine，Wuhan 430061，China;

2 Department of Hepatology，Hubei Provincial Hospital of Traditional Chinese Medicine，Wuhan 430061，China）

Abstract 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.

Keywords Network Pharmacology; Molecular Docking; Yinchen Wuling Powder; Primary Biliary Cholangitis; Primary Biliary Cirrhosis

中图分类号：R285.6文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.02.005

原发性胆汁性胆管炎又称原发性胆汁性肝硬化（Primary Biliary Cirrhosis，PBC），是一种由自身免疫性疾病引起的慢性非化脓性胆汁淤积性肝病。其发病机制复杂，病程较长。胆汁合成、转运、排泄等异常导致胆汁淤积，是PBC疾病发展的共同病理过程。胆汁酸和其他毒性代谢产物在肝脏或体循环中异常堆积，发为包括PBC在内的胆汁淤积性疾病，引起肝细胞损伤、肝内胆管的炎性反应、肝纤维化，最终发展为肝硬化、肝癌、胆管癌等[1]。

目前，临床仍缺乏特异性高、疗效好、不良反应小的治疗药物。法尼醇X受体（Farnesoid X receptor，FXR）是目前治疗PBC认可度较高的靶标。……