基于网络药理学和分子对接探讨真人养脏汤对溃疡性结肠炎的作用机制

Mechanism of action of Zhenren Yangzang decoction in treatment of ulcerative colitis:A study based on network pharmacology and molecular docking

目的:基于网络药理学和分子对接技术探讨真人养脏汤治疗溃疡性结肠炎(UC)的作用机制。方法:通过TCMSP数据库检索人参、当归、白术、肉豆蔻、肉桂、白芍、木香、诃子、罂粟壳的活性成分及靶点;运用DisGeNET数据库筛选出UC的相关靶点;使用Venny 2.1平台筛选共同靶点,导入Cytoscape 3.8.0软件构建真人养脏汤成分-靶点网络可视化关系图,筛选出核心成分;依据STRING数据库得到共同靶点的蛋白互作网络,筛选出核心靶点;采用DAVID 6.7数据库对共同靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析;同时将筛选得到的核心成分和核心靶点进行分子对接验证。结果:筛选出真人养脏汤治疗UC的核心成分为山柰酚、谷甾醇、豆甾醇、可待因、碎叶紫堇碱、蓝堇碱;核心靶点为蛋白激酶(AKT1)、白细胞介素-6(IL-6)、血管内皮生长因子(VEGFA)、肿瘤坏死因子(TNF)、肿瘤蛋白p53(TP53);信号通路主要涉及TNF、低氧诱导因子-1(HIF-1)、Toll样受体(TLR)等,分子对接显示核心成分和核心靶点具有较强的结合能力。结论:本研究初步揭示了真人养脏汤治疗UC的作用机制,为后续研究提供思路与依据。

Objective:To investigate the mechanism of action of Zhenren Yangzang decoction in the treatment of ulcerative colitis(UC)based on network pharmacology and molecular docking.Methods:TCMSP database was used to obtain the active components and targets of Panax ginseng,Angelica sinensis,Atractylodes macrocephala Koidz.,Myristica fragrans,cinnamon,Radix Paeoniae Alba,Saussurea costus,Chebulae Fructus,and Papaveris Pericarpium,and DisGeNET database was used to obtain the targets of UC.Venny 2.1 platform was used to obtain the common targets,which were imported into Cytoscape 3.8.0 software to construct a visualized component-target network for Zhenren Yangzang decoction,and core components were screened out.STRING database was used to establish the protein-protein interaction network of the common targets and obtain the core targets.DAVID 6.7 database was used to perform gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses,and molecular docking validation was performed for the core components and the core targets.Results:The core components of Zhenren Yangzang decoction in the treatment of UC were kaempferol,sitosterol,stigmasterol,codeine,cheilanthifoline,and fumarine,and the core targets were AKT1,interleukin-6,vascular endothelial growth factor,tumor necrosis factor(TNF),and tumor protein p53.Signaling pathways mainly involved TNF,hypoxia-inducible factor-1,and Toll-like receptor.Molecular docking showed a relatively strong binding capacity between the core components and the core targets.Conclusion:This study preliminarily reveals the mechanism of action of Zhenren Yangzang decoction in the treatment of UC,which provides ideas and a basis for subsequent studies.