目的 通过网路药理学和分子对接探讨葛根调控溃疡性结肠炎的作用机制。方法 通过TCMSP数据库、Uniprot数据库检索葛根有效成分及靶点,通过OMIM、DisGeNET、DrugBank及GeneCards数据库检索溃疡性结肠炎的靶点。采用Cytoscape 3.8.2软件构建"药物-成分-靶点-疾病"关系网络,并将葛根调控溃疡性结肠炎的相关靶点基因导入String数据库构建蛋白互作(PPI)网络。通过Metascape数据库进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)基因富集分析,得到葛根调控溃疡性结肠炎的潜在作用通路,再通过分子对接验证活性成分与核心靶点的结合能力。结果 从葛根中筛选出5个潜在的活性成分,共有60个靶点作用于溃疡性结肠炎,葛根成分靶点中拓扑分析和通路富集分析发现葛根可通过炎症相关靶点及作用通路发挥治疗溃疡性结肠炎的作用;分子对接结果显示,葛根素和刺芒柄花素与关键靶点蛋白(PTGS2、JUN、TNF、STAT3、PTGS2、JUN)的结合能力较强。结论 葛根调控溃疡性结肠炎具有可行性,可与其他药物配伍治疗溃疡性结肠炎。

Objective To explore the mechanism of Pueraria lobata regulating ulcerative colitis through network pharmacology and molecular docking. Methods The effective components and targets of Pueraria lobata were searched by TCMSP database and Uniprot database, and the targets of ulcerative colitis were searched by OMIM, DisGeNET, DrugBank and GeneCards database. Cytoscape3.8.2 software was used to construct the relationship network of “drug-component-target-disease”. The protein interaction (PPI) network was constructed by importing the related target genes of Pueraria lobata regulating ulcerative colitis into String database. Gene enrichment analysis was conducted by Metascape database for gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to obtain the potential pathway of Pueraria lobata regulating ulcerative colitis, and the binding ability of active ingredients to core targets was verified by molecular docking. Results Five potential active components were screened from Pueraria lobata, and a total of 60 targets acted on ulcerative colitis. Topology analysis and pathway enrichment analysis of Pueraria lobata component targets showed that pueraria could play a role in treatment of ulcerative colitis through inflammatory targets and pathways. Molecular docking results showed that puerarin and formononetin had strong binding ability to key target proteins (PTGS2, JUN, TNF, STAT3, PTGS2, JUN). Conclusion Pueraria lobata regulation of ulcerative colitis is feasible, and can be combined with other drugs in the treatment of ulcerative colitis.

R285.2

山东省重点研发计划（重大科技创新工程）项目（2020CXGC010505）