摘要
目的运用网络药理学方法及分子对接技术,对玉女煎治疗糖尿病的作用机制进行分析和探讨。方法通过查询TCMSP和BATMAN-TCM数据库,对玉女煎组方中的5种药物所含有效成分及作用靶点进行筛选,并借助Uniprot数据库对查得靶点进行基因注释。通过查询DisGeNET数据库,筛选糖尿病相关靶点。对药物基因与疾病基因取交集即得玉女煎治疗糖尿病的潜在靶点,借助Cytoscape 3.7.2软件构建“疾病-药物-成分-靶点”可视化网络。利用STRING 11.5平台构建靶点蛋白相互作用(PPI)网络,并借助David数据库对靶点分别进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。运用AutoDockTools-1.5.6软件测算关键成分与核心靶点的结合能力。结果玉女煎对糖尿病起到治疗作用的关键活性成分为槲皮素、豆甾醇、山奈酚、汉黄芩素、黄芩素和薯蓣皂素。核心靶点为血管内皮生长因子A(VEGFA)、肿瘤坏死因子(TNF)、白细胞介素-6(IL6)、前列腺素内过氧化物合酶2(PTGS2)、肿瘤抑制蛋白P53(TP53)、白细胞介素1β(IL1B)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、胱天蛋白酶3(CASP3)、趋化因子配体2(CCL2)和瘦素(LEP)。涉及的关键生物学过程包括基因表达的正调控、基因表达的负调控、一氧化氮生物合成过程的正调控、平滑肌细胞增殖的正调控和低氧状态下的细胞应答等。涉及的关键通路包括糖尿病并发症中的晚期糖基化终末产物(AGE)-糖基化终末产物受体(RAGE)信号通路、细胞流体切应力与动脉粥样硬化信号通路、癌症信号通路、缺氧诱导因子-1(HIF-1)信号通路和胰岛素抵抗信号通路等。各关键成分与核心靶点结合良好且构象稳定。结论玉女煎可能通过作用于VEGFA、TNF、IL6、PTGS2、TP53、IL1B、AKT1、CASP3、CCL2和LEP等靶点,调控AGE-RAGE、HIF-1和胰岛素抵抗等信号通路,发挥对糖尿病的疗效。
OBJECTIVE To analyze and explore the mechanism of YuNv Decoction in the treatment of diabetes with network pharmacology and molecular docking method.METHODS The effective components and targets of five traditional Chinese medicines in YuNv Decoction were screened from TCMSP database and BATMAN-TCM database.Gene annotation of the targets was conducted with UniProt database.Potential diabetes related targets were screened from DisGeNET database.The intersection genes of drug and disease may be the potential targets of YuNv Decoction in the treatment of diabetes.The visual“disease-drug-compound-target”network was constructed with Cytoscape 3.7.2.The visual protein-protein interaction(PPI)network was constructed on STRING 11.5 platform.Gene ontology(GO)functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed through David database.AutoDockTools-1.5.6 was used to test the combination ability of YuNv Decoction′s core components and targets.RESULTS The core active components of YuNv Decoction in the treatment of diabetes were quercetin,stigmasterol,kaempferol,wogonin,baicalein and diosgenin.The core targets were VEGFA,TNF,IL6,PTGS2,TP53,IL1B,AKT1,CASP3,CCL2 and LEP.The involved key biological processes included positive regulation of gene expression,negative regulation of gene expression,positive regulation of nitric oxide biosynthetic process,positive regulation of smooth muscle cell proliferation,cellular response to hypoxia,etc.The involved key pathways included AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis pathway,pathways in cancer,HIF-1 signaling pathway,insulin resistance pathway,etc.The core components and targets firmly combined with each other and kept in a steady situation.CONCLUSION YuNv Decoction may achieve the treatment efficacy of diabetes by regulating the AGE-RAGE signaling pathway in diabetic complications,HIF-1 signaling pathway and insulin resistance pathway through actions on VEGFA,TNF,IL6,PTGS2,TP53,IL1B,AKT1,CASP3,CCL2,LEP,etc.
作者
左瑶瑶
梅丹
韩黎黎
ZUO Yao-yao;MEI Dan;HAN Li-li(Department of Pharmacy,Affiliated Tumor Hospital of Nantong University,Nantong 226361,China)
出处
《海峡药学》
2023年第5期20-26,共7页
Strait Pharmaceutical Journal
基金
江苏省药学会-天晴医院药学基金项目(Q202040)。
关键词
玉女煎
网络药理学
糖尿病
作用机制
分子对接
YuNv Decoction
Network pharmacology
Diabetes
Mechanism
Molecular docking
