基于网络药理学探索附子理中汤治疗溃疡性结肠炎的作用机制

Mechanism of Fuzilizhong Decoction on the Treatment of Ulcerative Colitis by Network Pharmacology

摘要: 目的：运用网络药理学探讨附子理中汤治疗溃疡性结肠炎(Ulcerative Colitis, UC)的潜在作用机制。方法：利用中药系统药理学数据库与分析平台(TCMSP)获得附子理中汤的化学成分和作用靶点蛋白，通过DisGeNET、OMIM数据库检索获取UC疾病的相关靶点，利用venny2.1.0在线作图工具对药物和疾病的靶点进行映射，使用STRING数据库构建蛋白互作(PPI)网络，利用Metascape在线作图软件对交集靶点进行GO生物过程分析和KEGG通路富集分析，并使用R软件及Cytoscape软件对结果进行绘图可视化。结果：筛选得到附子理中汤中药活性化学成分104个，与UC相关的活性化学成分98个，与UC共同作用靶点107个；PPI网络涉及89节点，452条边，得到STAT3、JUN、TNF等十个核心靶点；GO功能富集分析得到2157条GO目条，其中生物过程(BP) 1978条，分子功能(MF) 124条，细胞组分(CC) 55条，包括对炎症的反应、对脂多糖的反应、对细菌原分子的反应和活性氧代谢等；KEGG富集筛选得到164条信号通路，主要有AGE-RACE信号通路(AGE-RAGE signaling pathway in diabetic complications)、白细胞介素信号17通路(IL-17 signaling pathway)、肿瘤坏死因子信号通路(TNF signaling pathway)、HIF-1信号通路(HIF-1 signaling pathway)等信号通路，主要与代谢、免疫炎症以及氧化应激相关。结论：附子理中汤治疗UC主要是通过槲皮素、山萘酚、柚皮素、刺芒柄花素、甘草查尔酮a等活性成分作用于STAT3、JUN、TNF等关键靶点基因从而调节多条生物学功能与信号通路，最终达到治疗溃疡性结肠炎的作用。

Abstract: Objective: To explore the mechanism of Fuzilizhong decoction (FLD) in the treatment for ulcera-tive colitis (UC) by Network pharmacology. Methods: The known components and associated targets of FLD were obtained from TCMSP database. The disease targets for UC were obtained from the DisGeNET, OMIM databases. Effective targets were obtained after mapping the above two parts of targets by using venny 2.1.0 online mapping tool. The protein-protein interaction (PPI) network was constructed from STRING database. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) analysis were conducted through Metascape, the results were visualized by Cytoscape and R softwares. Results: Through screening, 104 main active components of FLD were obtained, only 98 active components related to the UC disease, and 107 targets were related to the UC disease. A total of 89 nodes and 452 edges were involved in the PPI network. 10 key targets were obtained, such as STAT3, JUN, TNF and so on. Metascape was used for GO enrichment analysis and the results showed that there were 1978 biological processes, 124 molecular functions and 55 cell components, including inflammatory response, response to lipopolysaccharide, response to molecule of bacterial origin and reactive oxygen species metabolic process and so on. Enrichment analysis of KEGG showed that there were 164 signal pathways such as AGE-RAGE, IL-17, TNF, HIF-1 signal pathways, which were mainly related to metabolism, immune inflammation and oxidative stress. Conclusion: Fuzilizhong Decoction in the treatment of ulcerative colitis mainly through quercetin, kaempferol, naringenin, formononetin, licochalconea acts on STAT3, JUN, TNF, so as to regulate multiple biological functions and signal pathways, and finally achieve the therapeutic effect.