基于网络药理学、分子模拟和体外实验探讨厚朴七物汤治疗溃疡性结肠炎的作用机制*

作者：徐敏嫦1，陈转艮1，梁俊杰1，陈航海2，汤瑞珠1，蓝燕红1

单位：1.南方医科大学第十附属医院（东莞市人民医院），广东 东莞 523059； 2.深圳市计量质量检测研究院食品快检与核查事业部，广东 深圳 518055

引用：引用：徐敏嫦，陈转艮，梁俊杰，陈航海，汤瑞珠，蓝燕红.基于网络药理学、分子模拟和体外实验探讨厚朴七物汤治疗溃疡性结肠炎的作用机制[J].中医药导报,2025,31(12):34-40.

DOI：10.13862/j.cn43-1446/r.2025.12.006

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摘要：

目的：采用网络药理学、分子模拟技术及体外实验验证厚朴七物汤治疗溃疡性结肠炎（UC）的分子机制。方法：通过TCMSP数据库获取厚朴七物汤化学成分及靶点，GEO数据库筛选UC差异基因，取二者交集。通过STRING数据库构建靶点互作网络，应用R语言及Cytoscape进行KEGG与GO通路富集分析，构建“中药-成分-疾病-靶点-通路”网络。采用AutoDock对主要活性成分与关键靶点进行分子对接分析。构建UC相关细胞模型，验证有效成分对TNF-α促进肠炎的干预作用。结果：筛选获得厚朴七物汤与UC共有靶点120个，进一步筛选出7个关键靶点：CD36、IFNG、IL1B、IL6、PPARG、PTGS2、TNF，主要富集于炎症相关及PPARG核受体代谢通路。分子对接和CETSA实验显示，熊果酸（Ursolic acid）与TNF-α稳定结合。体外实验证实，熊果酸能显著减弱TNF-α对肠道屏障的破坏作用，上调紧密连接蛋白ZO-1和E-cadherin表达，增强肠上皮细胞跨膜电阻。结论：厚朴七物汤治疗UC主要通过调控TNF-α等多个炎症通路及上调屏障蛋白发挥作用，熊果酸可能是其主要活性成分。

关键词：溃疡性结肠炎；厚朴七物汤；网络药理学；分子模拟；作用机制

Abstract：

Objective: To investigate the molecular mechanism of Huopo Qiwu decoction (HPQWD) in treating ulcerative colitis (UC) using network pharmacology, molecular simulation techniques, and in vitro validation. Methods: Chemical components and targets of HPQWD were obtained from the TCMSP database, and UC-related differential genes were screened from the GEO database. The intersection targets were identified. Target-target interaction networks were constructed using the STRING database. KEGG pathway and GO enrichment analyses were performed using R language and Cytoscape to establish the "herb-component-disease-target-pathway" network. AutoDock was employed for molecular docking analysis between active components and key targets. UC-related cell models were constructed to verify the intervention effects of active components on TNF-α-induced colitis. Results: A total of 120 common targets between HPQWD and UC were identified, from which seven key targets were further screened, including CD36, IFNG, IL1B, IL6, PPARG, PTGS2 and TNF. These targets were primarily enriched in inflammation-related pathways and PPARG nuclear receptor metabolic pathways. Molecular docking and CETSA experiments demonstrated that ursolic acid stably bound to TNF-α. In vitro experiments confirmed that ursolic acid significantly attenuated TNF-α-induced intestinal barrier disruption, upregulated tight junction proteins ZO-1 and E-cadherin expression, and enhanced transepithelial electrical resistance in intestinal epithelial cells. Conclusion: HPQWD exerts its therapeutic effect on UC primarily by regulating multiple inflammatory pathways including TNF-α signaling and upregulating barrier proteins. Ursolic acid may be a key active component in this formula.

Key words：ulcerative colitis; Houpo Qiwu decoction; network pharmacology; molecular simulation; mechanism

发布时间：2026-01-30

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