目的 通過網(wǎng)路藥理學和分子對接探討葛根調(diào)控潰瘍性結(jié)腸炎的作用機制。方法 通過TCMSP數(shù)據(jù)庫、Uniprot數(shù)據(jù)庫檢索葛根有效成分及靶點,通過OMIM、DisGeNET、DrugBank及GeneCards數(shù)據(jù)庫檢索潰瘍性結(jié)腸炎的靶點。采用Cytoscape 3.8.2軟件構(gòu)建"藥物-成分-靶點-疾病"關(guān)系網(wǎng)絡(luò),并將葛根調(diào)控潰瘍性結(jié)腸炎的相關(guān)靶點基因?qū)隨tring數(shù)據(jù)庫構(gòu)建蛋白互作(PPI)網(wǎng)絡(luò)。通過Metascape數(shù)據(jù)庫進行基因本體論(GO)和京都基因和基因組百科全書(KEGG)基因富集分析,得到葛根調(diào)控潰瘍性結(jié)腸炎的潛在作用通路,再通過分子對接驗證活性成分與核心靶點的結(jié)合能力。結(jié)果 從葛根中篩選出5個潛在的活性成分,共有60個靶點作用于潰瘍性結(jié)腸炎,葛根成分靶點中拓撲分析和通路富集分析發(fā)現(xiàn)葛根可通過炎癥相關(guān)靶點及作用通路發(fā)揮治療潰瘍性結(jié)腸炎的作用;分子對接結(jié)果顯示,葛根素和刺芒柄花素與關(guān)鍵靶點蛋白(PTGS2、JUN、TNF、STAT3、PTGS2、JUN)的結(jié)合能力較強。結(jié)論 葛根調(diào)控潰瘍性結(jié)腸炎具有可行性,可與其他藥物配伍治療潰瘍性結(jié)腸炎。

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

山東省重點研發(fā)計劃（重大科技創(chuàng)新工程）項目（2020CXGC010505）