[关键词]
[摘要]
【目的】 借助网络药理学和分子对接技术,分析降糖三黄片治疗糖尿病视网膜病变的可能机制。【方法】 使用 TCMSP、 SwissADME、ETCM 2.0、BATMAN-TCM、化源网、化学专业网站、SwissTargetPrediction及Uniprot等数据库和平台,识别和筛 选降糖三黄片的活性成分及对应的作用靶标。使用 GeneCards、TTD、OMIM 数据库查找糖尿病视网膜病变相关靶标。通过 Venny 2.1平台确定降糖三黄片与疾病的共同靶标,并使用STRING平台建立蛋白质-蛋白质相互网络,从中挑选核心作用靶标。 应用DAVID数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)路径分析,并利用Cytoscape 3.9.1软件构建中 药-活性成分-靶标-信号通路-疾病的网络模型,进一步选取关键活性成分。最终通过AutoDock Vina 1.1.2软件进行分子对 接,探讨关键活性成分与核心靶标的相互作用。【结果】 共查找出467个潜在活性成分和309个共有靶标,这些靶标参与了多种 生物过程和信号途径。关键活性成分包括槲皮素、芹菜素、木犀草素、异甘草黄酮醇、香叶木素等。主要作用于核心靶标IL6、 AKT1、STAT3、EGFR和TP53。涉及癌症途径、前列腺癌途径、血脂与动脉粥样硬化途径、AGE-RAGE途径和乙型肝炎途 径等通路。【结论】 降糖三黄片可能通过槲皮素、芹菜素、木犀草素、异甘草黄酮醇、香叶木素等关键活性成分,作用于IL6、 AKT1、STAT3、EGFR、TP53等核心靶点,调节糖尿病视网膜病变相关的肿瘤相关通路以及AGE/RAGE信号通路、PI3K/AKT 信号通路、HIF-1信号通路、FoxO信号通路、MAPK信号通路等,发挥抑制炎症、减少氧化应激、防止新生血管形成等作用。
[Key word]
[Abstract]
Objective To analyze the possible mechanisms of Jiangtang Sanhung Tablets in the treatment of diabetic retinopathy(DR)by using network pharmacology and molecular docking technology. Methods Databases and platforms such as TCMSP, SwissADME, ETCM 2.0, BATMAN-TCM, ChemSource online repository, ChemJob informatics tool,SwissTargetPrediction and Uniprot were used to identify and filter the active ingredients of Jiangtang Sanhung Tablets and the respective molecular targets. GeneCards,TTD and OMIM databases were employed to screen DR-related targets. The Venny 2.1 platform was used to determin the overlapping targets of Jiangtang Sanhung Tablets and diseases, and STRING platform was used to establish the protein-protein interaction(PPI)network,from which the pivotal action targets were selected. The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis was applied by using DAVID database, and Cytoscape 3.9.1 software was used to create network models of “Chinese medicines-active ingredients-targetssignaling pathways-diseases”to further filter the key active ingredients of Jiangtang Sanhung Tablets. Finally, molecular docking was performed by AutoDock Vina 1.1.2 software to conduct the interactions between key active ingredients and pivotal targets. Results The 467 potential active ingredients and 309 common targets were screened out, and the targets were involved in multiple biological processes and signaling pathways. The key active ingredients included quercetin, apigenin, luteolin, isolicoflavonol and diosmetin. Mainly act on the pivotal targets IL6,AKT1,STAT3,EGFR,and TP53. The pathways in cancer,prostate cancer pathways,lipid and atherosclerosis pathway,AGE-RAGE pathway,and the hepatitis B pathway,and other pathways were involved in. Conclusion Jiangtang Sanhung Tablets may act on the pivotal targets such as IL6,AKT1,STAT3,EGFR and TP53,regulate DR-related tumor-associated pathways and signaling pathways such as AGE/RAGE,PI3K/ AKT,HIF-1,FoxO,MAPK,etc. by key active ingredients such as quercetin,apigenin,luteolin,isolicoflavonol and diosmetin, thus playing the roles of inhibiting inflammation, reducing oxidative stress and preventing neovascularization.
[中图分类号]
R285
[基金项目]
国家自然科学基金资助项目(编号:82174284)