基于网络药理学探讨芦荟治疗溃疡性结肠炎的作用机制

Exploring the Mechanism of Aloe in Treating Ulcerative Colitis Using Network Pharmacology

摘要: 目的：基于网络药理学方法，探索芦荟治疗溃疡性结肠炎(UC)的潜在活性成分与作用靶点，以期为临床应用提供理论依据。方法：借助中药系统药理学数据库(TCMSP)结合文献检索，筛选芦荟活性成分并预测其靶点；从GeneCards、OMIM等数据库中获取UC疾病相关靶点，将两者取交集获得共同靶点，利用Cytoscape软件构建“成分–靶点–疾病”相互作用网络，STRING数据库构建蛋白互作(PPI)网络，再使用CytoHubba插件筛选核心靶点。最后用DAVID数据库对共同靶点进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析。结果：共筛选出芦荟大黄素、芦荟酮等13个芦荟活性成分，对应214个作用靶点，与UC疾病靶点取交集后，获得97个共同作用靶点。网络分析提示芦荟大黄素等活性成分可能是关键；PPI网络分析确定TNF、IL6、IL1B、PTGS2、PPARG等为关键核心靶点。GO富集分析结果显示，这些靶点显著富集于炎症反应、活性氧代谢过程、细胞凋亡调控等生物过程。KEGG通路分析显示芦荟治疗UC的机制主要涉及IL-17信号通路、TNF信号通路、NF-κB信号通路、Toll样受体信号通路以及Th17细胞分化等通路。结论：本研究揭示了芦荟可能通过“多成分–多靶点–多通路”的方式发挥治疗UC的作用，其主要活性成分通过作用于核心靶点，调控炎症、免疫及细胞凋亡等多条信号通路，从而协同起效。预测结果与已有文献报道的芦荟药理活性高度吻合，为阐明其治疗UC的物质基础与作用机制提供了理论参考。

Abstract: Objective: To explore the potential active components and targets of Aloe vera in the treatment of ulcerative colitis (UC) based on network pharmacology, providing a theoretical basis for its clinical application. Methods: The active components of Aloe vera were screened and their targets predicted using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) combined with literature mining. UC-related disease targets were collected from databases including GeneCards and OMIM. The intersection of the component targets and disease targets was obtained to identify common targets. The “component-target-disease” interaction network was constructed using Cytoscape software, and a protein-protein interaction (PPI) network was built with the STRING database. The CytoHubba plugin was then employed to screen hub targets. Finally, Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the common targets using the DAVID database. Results: A total of 13 active components of Aloe vera, such as aloe-emodin and aloenin, were screened, corresponding to 214 potential targets. After intersecting with UC disease targets, 97 common targets were obtained. Network analysis suggested that components like aloe-emodin may be key active substances. PPI network analysis identified TNF, IL6, IL1B, PTGS2, and PPARG as core hub targets. GO enrichment analysis revealed that these targets were significantly enriched in biological processes such as inflammatory response, reactive oxygen species metabolic process, and regulation of apoptosis. KEGG pathway analysis indicated that the mechanisms of Aloe vera in treating UC primarily involve the IL-17 signaling pathway, TNF signaling pathway, NF-κB signaling pathway, Toll-like receptor signaling pathway, and Th17 cell differentiation. Conclusion: This study reveals that Aloe vera may exert therapeutic effects on UC through a “multi-component, multi-target, and multi-pathway” mode. Its main active components likely act on core targets, regulating multiple signaling pathways related to inflammation, immunity, and apoptosis, thereby producing synergistic effects. The prediction results are highly consistent with the reported pharmacological activities of Aloe vera, providing a theoretical reference for elucidating its material basis and mechanism in treating UC.