基于网络药理学探讨白薇和丁香对真菌性角膜炎的作用机制

To Explore the Mechanism of Action of Cynanchum atratum Bge and Syzygium aromaticum for Fungal Keratitis Based on Network Pharmacology

摘要: 目的：应用网络药理学方法研究白薇(Cynanchum atratum Bge, CA)和丁香(Syzygium aromaticum, SA)对治疗真菌性角膜炎(Fungal keratitis)的有效成分及其治疗机制。方法：通过中医药系统药理与分析平台(TCMSP)和BATMAN-TEM数据库收集CA/SA的主要有效成分和潜在靶点，应用GEO、OMIM、CTD、GenCLiP 3、DisGeNET、Malacards和Genecards数据库检索FK的治疗靶点。通过String和Cytoscape 3.7.2构建蛋白质–蛋白质相互作用(protein-protein interaction)网络，从而研究CA/SA潜在靶点与FK靶点之间的相互作用。此外，使用R软件、David和WebGestalt分析了基因本体论(Gene Ontology)和京都基因和基因组百科全书(Kyoto encyclopedia of Genes and Genomes)丰富信号通路。结果：共搜索到71个已分离鉴定的白薇化学成分及434个丁香化学成分，角膜炎相关靶点2031个，白薇和丁香治疗真菌性角膜炎的潜在靶点135个，包含20个直接作用靶点。构建出“成分–靶点–疾病”网络后发现白薇和丁香对治疗真菌性角膜炎与32个靶基因密切相关，GO功能富集分析与KEGG通路富集分析结果显示白薇和丁香对治疗真菌性角膜炎可能涉及的GO功能134个，信号通路主要包括肿瘤坏死因子信号通路、IL-17通路、Toll受体信号通路、Th17细胞分化通路、HIF-1信号通路等，绘制“CA/SA关键靶点–主要通路–FK”可视化网络图，显示出白薇、丁香和真菌性角膜炎与77个共同关键靶点、20条关键靶点作用的通路密切相关。结论：本研究预测了白薇和丁香的活性成分及潜在靶点，对于白薇和丁香对真菌性角膜炎的潜在作用及机制进行了初步探索，为阐明白薇和丁香对真菌性角膜炎的机制提供了科学依据和参考。

Abstract: Objective: To investigate the active ingredients and the therapeutic mechanisms of Cynanchum atratum Bge (CA) and Syzygium aromaticum (SA) on fungal keratitis (FK) by using a network phar-macology approach. Methods: In this study, the main active ingredients and potential targets of CA/SA were collected through the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and BATMAN-TCM databases. Therapeutic targets of FK were retrieved by using the GEO, OMIM, CTD, GenCLiP 3, DisGeNET, Malacards and Genecards databases. Protein- protein in-teraction (PPI) network was constructed to concern the interactions of potential targets of CA/SA with targets of FK through the String and Cytoscape 3.7.2. Furthermore, R software, David and WebGestalt were used to analyze gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment. Results: A total of 71 isolated and identified chemical com-ponents of CA and 434 chemical components of SA, 2031 targets related to keratitis, 135 potential targets of CA and SA in the treatment of fungal keratitis were searched, including 20 direct targets. After constructing the “component-target-disease” network, it was found that CA and SA were closely related to 32 target genes in the treatment of fungal keratitis. The results of GO function en-richment analysis and KEGG pathway enrichment analysis showed that CA and SA might be in-volved in 134 GO functions for the treatment of fungal keratitis. The signal pathways mainly include tumor necrosis factors signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway, Th17 cell differentiation signaling pathway, HIF-1 signaling pathway and so on. The visual network map of “CA/SA key target-main pathway-FK” was drawn. The results showed that CA/SA and fungal keratitis were closely related to 77 common key targets and 20 key targets. Conclusion: This study predicted the active components and potential targets of CA and SA, and explored the potential effect and mechanism of CA and SA on fungal keratitis, which provided scientific basis and reference for elucidating the mechanism of CA and SA on fungal keratitis.