溃疡性结肠炎（UC）是结肠粘膜的慢性炎症性肠病。七叶亭是一种天然香豆素，具有抗氧化、抗癌、抗炎等多种药理活性。之前的研究表明，七叶亭可改善UC中的肠道炎症并降低血清促炎细胞因子。本研究旨在利用网络药理学和分子对接来探讨七叶亭抗UC的潜在机制。通过 SwissTargetPrediction 和 Super-PRED 网络服务器预测七叶亭的潜在基因靶点。 UC相关基因从DisGeNet、OMIM和GeneCards数据库获得。七叶亭的基因靶点与UC相关基因之间的重叠被确定为七叶亭抗UC的潜在靶点。通过STRING数据库分析这些重叠基因之间的相互作用，并通过Cytoscape平台识别核心基因。然后对核心基因进行基因本体论和京都基因和基因组百科全书途径富集分析。这些分析结果通过分子对接得到了进一步证实。总共确定了 50 个重叠基因作为七叶亭对抗 UC 的潜在作用靶点。其中，最终确定10个基因（AKT1、STAT1、CCND1、SRC、PTGS2、EGFR、NFKB1、ESR1、MMP9、SERPINE1）为核心基因。京都基因与基因组百科全书通路富集分析结果显示，与七叶亭抗UC核心基因相关的顶级信号通路是催乳素（PRL）信号通路。分子对接结果表明七叶素与核心基因以及PRL和催乳素受体具有很强的结合亲和力。本研究提示七叶亭可能通过PRL信号通路对UC产生至关重要的影响，并为七叶亭治疗UC的潜在机制提供了见解，从而可能为UC的机制和治疗提供线索。版权所有©2023作者( s）。由 Wolters Kluwer Health, Inc. 出版

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of the colonic mucosa. Esculetin is a type of natural coumarin that has many pharmacological activities such as antioxidant, anticancer, anti-inflammatory, etc. A previous study showed that esculetin improved intestinal inflammation and reduced serum proinflammatory cytokines in UC. The present study aimed to utilize network pharmacology and molecular docking to explore the potential mechanism of esculetin against UC. The potential gene targets of esculetin were predicted through SwissTargetPrediction and Super-PRED web servers. UC-related genes were obtained from DisGeNet, OMIM, and GeneCards databases. The overlap between gene targets of esculetin and UC-related genes were identified as the potential targets of esculetin against UC. The interaction between these overlapping genes was analyzed by the STRING database and the core genes were identified by Cytoscape platform. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the core genes were then performed. And the results of these analyses were further confirmed through molecular docking. A total of 50 overlapping genes were identified as the potential action targets of esculetin against UC. Among them, 10 genes (AKT1, STAT1, CCND1, SRC, PTGS2, EGFR, NFKB1, ESR1, MMP9, SERPINE1) were finally identified as the core genes. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis results showed that the top signaling pathway associated with the core genes of esculetin against UC was the prolactin (PRL) signaling pathway. Molecular docking results showed that esculetin has a strong binding affinity to the core genes, as well as PRL and prolactin receptor. This study suggests that esculetin may have a crucial impact on UC through the PRL signaling pathway and provides insights into the potential mechanism of esculetin in the treatment of UC, which may shed light on the mechanism and treatment of UC.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.