基于网络药理学和分子对接研究半夏泻心汤治疗复发性口腔溃疡的作用机制

Study on the Mechanism of Banxia Xiexin Decoction in Treatment of Recurrent Oral Ulcers Based on Network Pharmacology and Molecular Docking

摘要: 目的：基于网络药理学和分子对接研究半夏泻心汤治疗复发性口腔溃疡的有效活性成分及分子机制。方法：利用中药系统药理学数据库(traditional Chinese medicine systems pharmacology database and analysis platform, TCMSP)检索半夏泻心汤组成药物有效成分及靶点；利用Genecard数据库获取复发性口腔溃疡疾病靶点；半夏泻心汤和复发性口腔溃疡靶点分别导入Venny2.1.0获得交集基因靶点，将交集靶点导入STRING数据库构建半夏泻心汤–复发性口腔溃疡蛋白相互作用(PPI)网络；利用Cytoscape3.9.2软件绘制前8核心靶点图，分析半夏泻心汤–组成–有效成分–交集靶点–复发性口腔溃疡相互关系并进行可视化；利用DAVID数据库分析基因本体论(gene ontology, GO)和京都基因与基因组百科全书(KEGG)通路富集情况，采用微生信绘制GO富集柱状图，采用OmicShare Tools云工具绘制KEGG富集高级气泡图。利用分子对接技术对化合物和关键靶点的结合潜力进行验证。结果：共筛选半夏泻心汤有效成分211个及组成药物共靶点230个，复发性口腔溃疡疾病靶点4773个，交集基因靶点196个；交集靶点GO富集分析，共获得899条GO注释(P < 0.01)，其中693条与生物过程有关、67条与细胞组分有关，139条与分子功能有关；KEGG通路分析，共获得127条KEGG信号通路(P < 0.01)；根据P值大小筛选GO前10、KEGG前20分别进行可视化。结论：半夏泻心汤可能是通过有效成分11,13-Eicosadienoic acid、methyl ester、gadelaidic acid、Chrysanthemaxanthin等作用于STAT3、AKT1、TP53等关键基因靶点，参与细胞对药物的反应、RNA聚合酶II启动子转录的正调控、对乙醇的反应等生物过程，经TNF信号通路、Toll样受体信号通路、HIF-1信号通路等主要通路发挥作用治疗复发性口腔溃疡疾病。

Abstract: Objective: To study the effective active ingredients and molecular mechanism of Banxia Xiexin Decoction in the treatment of recurrent oral ulcers based on network pharmacology and mole-cular docking. Methods: Use the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) to retrieve the active ingredients and targets of the constituent medicines of Banxia Xiexin Decoction; Use Genecard database to obtain disease targets for re-current oral ulcers; Banxia Xiexin Decoction and recurrent oral ulcer targets were imported into Venny 2.1.0 to obtain the intersection gene targets, and the intersection targets were imported into the STRING database to construct the Banxia Xiexin Decoction-recurrent oral ulcer protein interaction (PPI) network; Use Cytoscape 3.9.2 software to draw the top 8 core target maps, analyze and visualize the relationship between Banxia Xiexin Decoction-composition-active in-gredients-intersection target-recurrent oral ulcer; Use DAVID database to analyze gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment, use Weishengxin to draw GO enrichment histogram and use OmicShare Tools cloud tool to draw KEGG enrichment high-level bubble charts. Molecular docking technology was used to verify the binding potential of compounds to key targets. Results: A total of 211 active ingredients of Banxia Xiexin Decoction and 230 drug targets, 4773 targets for recurrent oral ulcer disease, and 196 intersecting gene targets were screened; A total of 899 GO annotations were obtained by GO enrichment analysis of intersection targets (P < 0.01), among which 693 were related to biological processes, 67 were related to cellular components, and 139 were related to molecular functions; By KEGG pathway analysis, a total of 127 KEGG signaling pathways were obtained (P < 0.01); According to the size of the P value, the top 10 GO and the top 20 KEGG were screened for visualization. Conclusion: Banxia Xiexin Decoction may act on key gene targets such as STAT3, AKT1 and TP53 through the active ingredients 11,13-Eicosadienoic acid, methyl ester, gadelaidic acid, chrysanthemaxanthin etc., participate in cell reaction to drugs, positive regulation of RNA polymerase II promoter transcription, reaction to ethanol and other biological processes, and treat recurrent oral ulcer disease through TNF signaling pathway, Toll-like receptor signaling pathway, HIF-1 signaling pathway, and other major pathways.