黄芩汤（HQD）是一种用于治疗结肠炎和结直肠癌（CRC）的中药。然而，尽管HQD具有良好的临床疗效，但其具体成分和机制仍不清楚。本研究旨在通过生物信息学、网络药理学和实验，探讨溃疡性结肠炎（UC）与结肠炎相关结直肠癌（CAC）的进展机制，同时检验 HQD 及其化合物对此的保护作用。验证了 UC 和 CRC 之间的枢纽基因及其临床预测意义、功能和表达。利用网络药理学与枢纽基因相结合，确定了 HQD 预防 UC 发展为 CAC 的关键靶点。利用分子对接和分子动力学（MD）来获得能够有效结合这些靶标及其转录因子（TF）的化合物。最后，在UC或CAC小鼠中证明了关键靶标的表达和机制。(1)联合分析UC和CRC基因集，得到14个hub基因，主要与细胞外基质受体结合、细胞外基质中的生物过程、粘着斑和中性粒细胞迁移； （2）网络药理学结果显示，HQD有133个治疗UC和CRC的核心靶点，作用于细胞外基质、炎症性肠病、化学致癌受体激活等途径； (3) hub基因与核心靶点的交叉产生了两个关键靶点MMP1和MMP3； (4) STAT3是MMP1和MMP3的共享TF。 (5)分子对接和MD验证光甘草定与STAT3/MMP1/MMP3的对接稳定可靠； (6) 小鼠体内实验证实，光甘草定通过抑制STAT3的磷酸化和调节MMP1/3的活性，减少炎症、细胞外基质降解和上皮间质转化的发生，防止UC转化为CAC。Copyright © 2024作者。由 Elsevier B.V. 出版。保留所有权利。

Huangqin decoction (HQD) is a Chinese medicine used to treat colitis and colorectal cancer (CRC). However, the specific compounds and mechanisms of HQD remain unclear despite its good curative clinical results. Through bioinformatics, network pharmacology, and experiments, this study aims to explore the progressive mechanisms of colitis-associated colorectal cancer (CAC) from ulcerative colitis (UC) while examining the protective effects of HQD and its compounds against this.Bioinformatics was utilized to identify the hub genes between UC and CRC, and their clinical predictive significance, function, and expression were validated. Employing network pharmacology in combination with hub genes, key targets of HQD for preventing the development of UC into CAC were identified. Molecular docking and molecular dynamics (MD) were utilized to procure compounds that effectively bind to these targets and their transcription factors (TFs). Finally, the expression and mechanism of key targets were demonstrated in mice with UC or CAC.(1) Joint analysis of UC and CRC gene sets resulted in 14 hub genes, mainly related to extracellular matrix receptor binding, biological processes in the extracellular matrix, focal adhesion and neutrophil migration; (2) Network pharmacology results show HQD has 133 core targets for treating UC and CRC, acting on extracellular matrix, inflammatory bowel disease, chemical carcinogen receptor activation and other pathways; (3) The intersection of hub genes and core targets yielded two key targets, MMP1 and MMP3; (4) STAT3 is a shared TF of MMP1 and MMP3. (5) Molecular docking and MD verified that the dockings between Glabridin and STAT3/MMP1/MMP3 are stable and reliable; (6) In murine vivo experiments verified that Glabridin reduces inflammation, extracellular matrix degradation, and the occurrence of epithelial-mesenchymal transition to prevent UC transforming into CAC by inhibiting the phosphorylation of STAT3 and regulating the activity of MMP1/3.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.