【摘要】 目的:利用网络药理学与动物实验方法探讨芍药甘草汤治疗溃疡性结肠炎(ulcerative colitis, UC)的潜在机制。方法:对芍药甘草汤治疗UC的有效成分和作用靶点进行筛选，构建成分-靶点相互作用网络，进行蛋白质相互作用关系分析，GO、KEGG信号通路富集分析；利用葡聚糖硫酸钠制备UC小鼠模型，观察芍药甘草汤对UC小鼠的药效作用，并进一步验证其机制。结果:筛选得到芍药甘草汤与UC的105个交集靶点，芍药甘草汤治疗UC的靶点显著富集于IL-17、TNF、PI3K-Akt、NF-κB、Wnt等信号通路中。动物实验结果显示，与模型组比较，芍药甘草汤组小鼠结肠缩短程度和体重减轻程度降低，DAI评分降低，结肠组织炎症因子TNF-α、IL-6 mRNA下降，Wnt/β-catenin通路相关基因MUC2、Wnt4、Wnt16 mRNA升高，肠道紧密连接蛋白ZO-1、Occludin以及Wnt/β-catenin通路相关蛋白β-catenin、p-GSK3β表达升高。结论:芍药甘草汤可通过Wnt/β-catenin信号通路改善肠道屏障功能治疗UC。更多还原

【Abstract】 Objective: This study aimed to elucidate the potential mechanism of action of Shaoyao Gancao decoction in the treatment of ulcerative colitis(UC), employing network pharmacology and animal experimentation. Methods: Active compounds and corresponding targets of Shaoyao Gancao decoction for UC treatment were identified. A component-target network was constructed and analyzed. Protein-protein interactions were assessed, and gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analyses were performed. The UC mouse model was established using dextran sodium sulfate(DSS) to evaluate the pharmacodynamic effects of Shaoyao Gancao decoction and to further validate its mechanism of action. Results: Network pharmacology analysis identified 105 overlapping targets between Shaoyao Gancao decoction and UC. Eenriched in signaling pathways implicated in UC pathogenesis, including interleukin-17(IL-17), tumor necrosis factor(TNF), phosphatidylinositol 3-kinase(PI3K)-Akt, nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB), Wnt signaling pathway, and so on. The results of the animal experiments demonstrated that, in comparison to the model group, the degree of colon shortening, body mass reduction, and DAI score were diminished in mice within the Shaoyao Gancao decoction group. The mRNA expression of pro-inflammatory cytokines TNF-α and IL-6 in colon tissues was downregulated, whereas transcriptional levels of Wnt/β-catenin pathway-associated genes(MUC2, Wnt4, Wnt16) showed significant upregulation. Similarly, the intestinal tight junction proteins ZO-1 and Occludin, as well as the Wnt/β-catenin pathway-related proteins β-catenin and p-GSK3β, were also increased. Conclusion: Shaoyao Gancao decoction may improve intestinal barrier function through modulation of the Wnt/β-catenin signaling pathway, suggesting a potential therapeutic strategy for UC.更多还原