基于网络药理学探讨昆仙胶囊治疗类风湿关节炎的作用机制

Mechanism of Kunxian capsule in the treatment of rheumatoid arthritis based on network pharmacology

目的采用网络药理学方法,探讨昆仙胶囊治疗类风湿关节炎(RA)的分子靶点及可能的作用机制。方法利用中药系统药理学数据库和分析平台(TCMSP)结合本草组鉴(HERB)检索昆仙胶囊所含中药的化学成分,并依据TCMSP数据库的口服生物利用度(OB)和类药性指数(DL)筛选出主要有效活性成分,并获取其对应的靶点。通过Genecards数据库与OMIM数据库筛选出RA的靶点,利用Venn图制作网站获取药物与疾病的共同靶点,运用Cytoscape构建“活性成分-靶点”网络;使用String数据库绘制靶蛋白相互作用(PPI)网络,利用Cytoscape软件中的ClueGo功能对公共靶点进行GO富集分析和KEGG富集分析。结果该研究共筛选出昆仙胶囊的有效活性成分81个,作用靶点913个,去除重复得到228个。从GeneCard数据库与OMIM数据库中获得RA的靶点4494个,通过交集获得公共靶点162个。揭示了槲皮素、木犀草素、山奈酚、β-谷甾醇及雷公藤甲素等5种成分是昆仙胶囊中的主要活性成分,AKT1、IL-10、STAT3、CASP8及CDKN1A可能是该药治疗RA的关键靶点。GO及KEGG富集分析结果显示,昆仙胶囊干预RA的作用机制主要与活性氧代谢过程的调控、激酶活性的调节、IL-17信号通路等有关,涉及感染、炎症及免疫的重要生物过程和信号通路。结论本研究从网络药理学角度,初步探讨了昆仙胶囊治疗RA的物质基础和作用机制,提示了其多成分、多靶点、多途径的整体调节特点,为后续分子生物学实验研究提供了思路与依据。

Objective To explore the molecular targets and associated potential pathways of Kunxian capsule in the treatment of rheumatoid arthritis(RA)based on network pharmacology.Methods The constituents of Kunxian capsule were searched by Traditional Chinese Medicine Systems Pharmacology Database,Analysis Platform(TCMSP)and a high-throughput experiment-and reference-guided database of traditional Chinese medicine(HERB).The potential active ingredients and targets were retrieved based on TCMSP database.RA related gene targets were retrieved through GeneCards database and OMIM database.Venn online software was used to obtain the common target of drugs and diseases.The“compound-target”network diagram was constructed with Cytoscape software.String database was used to draw the protein interaction(PPI)network.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the intersection network were conducted by Bioconductor Database.Results 81 active ingredients and 913 targets were identified.228 targets were obtained after removing the duplicates.4494 target genes directly related to RA were obtained from the GeneCards databases and OMIM databases.162 genes were obtained from the intersection of component-target and disease-target.It was revealed that five ingredients including quercetin,luteolin,kaempferol,β-sitosterol and triptolide are the main active ingredients in Kunxian capsule.AKT1,IL-10,STAT3,CASP8 and CDKN1A may be the main therapeutical targets.The results of GO and KEGG enrichment analysis showed that the mechanism of Kunxian capsule is mainly related to the regulation of reactive oxygen metabolism,the regulation of kinase activity,and IL-17 signaling pathway.The important biological processes and signaling pathways include infection,inflammation and immunity.Conclusion This research preliminarily explored the mechanism of Kunxian capsule in the treatment of RA by network pharmacology and suggested that the overall regulation is characterized by multi-components,multi-targets,and multi-channels.It provided some ideas for further molecular biology experiments.