基于网络药理学分析玉液汤治疗糖尿病视网膜病变的机制

Analysis of the Mechanism of Yuye Decoction in the Treatment of Diabetic Retinopathy Based on Network Pharmacology

摘要: 目的：分析玉液汤治疗糖尿病视网膜病变的主要活性成分、关键靶点和信号通路。方法：使用TCMSP数据库筛选玉液汤的主要活性成分和每个成分对应的靶点，无对应靶点的成分在SwissTargetPrediction数据库预测，将两个数据库的靶点进行整合。在GeneCards、DisGeNet数据库中收集糖尿病视网膜病变的靶点，通过Venny 2.1获得交集靶点。使用Cytoscape 3.9.1软件构建“药物–成分–靶点”的网络。运用STRING作蛋白互作分析，Cytoscape插件MCODE筛选关键靶点。在DAVID数据库中对关键靶点进行GO功能分析，使用R语言包对关键靶点进行KEGG信号通路分析。结果：共筛选出62个玉液汤的主要活性成分，260个交集靶点，13个关键靶点，192条信号通路。白桦脂酸、熊竹素、常春藤皂苷等是主要的活性成分，JAK1、EGFR、IGF1R、ERBB2等是治疗疾病的关键靶点。涉及糖尿病并发症的AGE/RAGE、PI3K/Akt、ErbB、JAK/STAT、VEGF、TNF、凋亡等信号通路的调控。结论：玉液汤可能通过多个生物过程以及介导多个信号通路调节细胞凋亡、细胞增殖、炎症反应、血管生成、免疫等过程进而治疗糖尿病视网膜病变。

Abstract: Objective: To analyze the main active components, key targets, and signaling pathways of Yuye Decoction in the treatment of diabetic retinopathy. Method: The TCMSP database was used to screen the main active components of Yuye Decoction and the corresponding targets of each component. The components without corresponding targets were predicted in the SwissTargetPrediction database, and the targets of the two databases were integrated. The targets of diabetic retinopathy were collected in the GeneCards and DisGeNet databases, and the intersection targets were obtained by Venny 2.1. The “drug-component-target” network was constructed using Cytoscape 3.9.1 software. STRING was used for protein interaction analysis, and the Cytoscape plug-in MCODE was used to screen key targets. GO function analysis of key targets was performed in the DAVID database, and KEGG signaling pathway analysis of key targets was performed using the R language package. Result: A total of 62 main active components of Yuye Decoction, 260 intersection targets, 13 key targets, and 192 signaling pathways were screened out. Mairin, Jaranol, and hederagenin are the main active components, and JAK1, EGFR, IGF1R, and ERBB2 are the key targets for the treatment of diseases. Regulation of AGE/RAGE, PI3K/Akt, ErbB, JAK/STAT, VEGF, TNF, apoptosis, and other signaling pathways involved in diabetic complications. Conclusion: Yuye decoction may regulate cell apoptosis, cell proliferation, inflammatory response, angiogenesis, immunity, and other processes through multiple biological processes and mediate multiple signaling pathways to treat diabetic retinopathy.