基于网络药理学的佛手干预2型糖尿病潜在靶点机制研究

Study on the Potential Target Mechanism of Fingered Citron Intervention in Type 2 Diabetes Mellitus Based on Network Pharmacology

目的基于网络药理学方法研究佛手干预2型糖尿病(type 2 diabetes mellitus,T2DM)的潜在作用靶点。方法利用TTD数据库、Drugbank数据库、OMIM数据库和DisGeNET数据库筛选T2DM相关基因,借助TCMSP数据库筛选佛手有效化学成分作为候选药效成分,通过COXPRESdb数据库及STRING筛选关键蛋白,运用Cytoscape 3.7.1软件构建疾病-药效成分-靶点-通路关系网络,使用DAVID 6.8数据库进行基因本体(gene ontology,GO)功能富集分析和KEGG通路富集分析,通过Vina将佛手候选药效成分与关键蛋白进行分子对接。结果①筛选得到181个疾病靶点候选基因、佛手6种有效成分、药效成分和疾病相关的25个关键蛋白,构建疾病-药效成分-靶点-通路关系网络;②GO功能富集分析得到GO条目57个(P≤0.05),其中生物过程条目43个,分子功能条目10个,KEGG通路富集得到10条通路(P≤0.05);③选取10个关键蛋白与佛手6个药效成分进行分子对接,结果显示其结合稳定。结论通过网络药理学研究发现,佛手通过6种有效成分,影响25个潜在靶点、10条相关通路,调节胆固醇生物合成和胰岛素分泌功能干预T2DM,为佛手作为"调肝启枢化浊"法主要药味治疗糖脂代谢病提供了依据,为其进一步的临床应用和深入研究开发提供了思路和线索。

Objective To explore potential action targets of Fructus Citri Sarcodactylis intervening in type 2 diabetes mellitus(T2 DM) based on network pharmacology. Methods TTD, Drugbank, OMIM and DisGeNET databases were used to screen related genes of T2 DM, and the TCMSP database was used to screen effective chemical components of Fructus Citri Sarcodactylis as candidate medicinal components. Key proteins were screened by the COXPRESdb database and STRING. A disease-medicinal component-target-pathway relation network was constructed by Cytoscape3.7.1 software. The David 6.8 database was used for analyses of gene ontology(GO) function enrichment and KEGG pathway enrichment. Molecular docking of the candidate medicinal components of Fructus Citri Sarcodactylis and the key proteins was performed through Vina. Results ①A total of 181 candidate genes of disease targets, 6 effective components and medicinal components of Fructus Citri Sarcodactylis and 25 key proteins related to the disease were screened out, and the disease-medicinal component-target-pathway relation network was constructed. ② The GO function enrichment analysis obtained 57 GO items(P ≤ 0.05), including 43 biological process items and 10 molecular function items. The KEGG pathway enrichment analysis obtained 10 pathways(P ≤ 0.05). ③The result in the molecular docking showed that combination of the 6 medicinal components of Fructus Citri Sarcodactylis and 10 selected key proteins was stable. Conclusion According to the study based on network pharmacology, it was found that Fructus Citri Sarcodactylis can regulate cholesterol biosynthesis and insulin secretion through 6 effective components affecting 25 potential targets and 10 related pathways, so as to intervene in T2 DM. It provides a basis for Fructus Citri Sarcodactylis as the main medicinal ingredient of the "regulating liver, activating the pivot and resolving turbidity" method in treating glycolipid metabolic disease, and provides the thinking and clue for its further clinical application and in-depth research and development.