当前位置:首页 / 基于网络药理学和分子对接技术探讨九味降糖口服液治疗糖尿病肾病的作用机制
论著.生物信息技术 | 更新时间:2024-03-19
|
基于网络药理学和分子对接技术探讨九味降糖口服液治疗糖尿病肾病的作用机制
Mechanism of Jiuwei Jiangtang Oral Liquid for the treatment of diabetic nephropathy: an exploration based on network pharmacology and molecular docking technique

广西医学 2023第45卷24期 页码:2998-3005

作者机构:陶晓静,硕士,主管药师,研究方向为药理学。

基金信息:广西中医药大学校级科研项目(2020QN022;2020MS053)

DOI:10.11675/j.issn.0253-4304.2023.24.12

  • 中文简介
  • 英文简介
  • 参考文献

目的 基于网络药理学和分子对接技术探讨九味降糖口服液治疗糖尿病肾病的作用机制。方法 在中药系统药理学数据库与分析平台、中医药整合药理学研究平台、本草组鉴数据库筛选九味降糖口服液各味中药的活性成分后,借助SwissTargetPrediction数据库和UniProt数据库获取其对应的作用靶点。在GeneCards及DisGeNET数据库检索糖尿病肾病相关靶点后,对两类靶点取交集。基于交集靶点,通过STRING数据库和Cytoscape 3.8.3软件构建蛋白-蛋白相互作用网络和药物-成分-靶点-疾病可视化调控网络,以分别筛选核心靶点和核心活性成分。通过Metascape数据库进行功能富集分析和通路富集分析。采用 AutoDockTools 1.5.7软件对核心活性成分与核心靶点蛋白进行分子对接验证。结果 共获得九味降糖口服液的活性成分84个,活性成分作用靶点1 078个,糖尿病肾病相关靶点613个,交集靶点共169个。核心活性成分为槲皮素、大豆苷元、葛根素、山柰酚、4′-甲氧基葛根素、异鼠李素、芒柄花素、β-谷甾醇、鞣花酸、京尼平苷、毛蕊异黄酮,核心靶点为GAPDH、肿瘤坏死因子(TNF)、白细胞介素(IL)-6、丝氨酸/苏氨酸蛋白激酶(AKT)1、血管内皮生长因子A(VEGFA)、肿瘤蛋白53(TP53)、IL-1β。富集分析结果显示,交集靶点主要参与对激素、肽、无机物、氮化合物的反应等生物过程,富集于膜筏、膜微区、质膜筏等细胞组分,主要涉及蛋白激酶活性、以醇为受体的磷酸转移酶活性、激酶活性等分子功能,并涉及磷脂酰肌醇3-激酶(PI3K)/AKT信号通路、糖尿病并发症中的晚期糖基化终末产物(AGE)-晚期糖基化终末产物受体(RAGE)信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、低氧诱导因子1(HIF-1)信号通路、TNF信号通路、IL-17信号通路等信号通路。分子对接结果显示,核心活性成分与核心靶点对接结果良好。结论 九味降糖口服液的多个活性成分可能通过作用于GAPDH、TNF、IL-6、AKT1、VEGFA、TP53、IL-1β等靶点,调控AGE-RAGE信号通路、PI3K/AKT信号通路、MAPK信号通路、HIF-1信号通路、TNF信号通路、IL-17信号通路等,从而影响炎症反应和氧化应激,进而影响糖尿病肾病的发生和发展。

ObjectiveTo explore the mechanism of Jiuwei Jiangtang Oral Liquid for the treatment of diabetic nephropathy based on network pharmacology and molecular docking technique.MethodsAfter screening the active components of various flavors of Traditional Chinese Medicines in Jiuwei Jiangtang Oral Liquid from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine, and Guided Database of Traditional Chinese Medicine, the SwissTargetPrediction database and UniProt database were used to obtain their corresponding effect targets. The GeneCards and DisGeNET databases were used to retrieve targets related to diabetic nephropathy, and then the intersection between the two categories of targets was acquired. On the basis of the intersection targets, the STRING database and Cytoscape 3.8.3 software were employed to establish protein-protein interaction network and drug-component-target-disease visual regulatory network for screening the core targets and the core active components, respectively. The functional enrichment analysis and pathway enrichment analysis were conducted by using the Metascape database. The molecular docking validation on the core active components and the proteins of core targets were conducted by using the AutoDockTools 1.5.7 software. ResultsA total of 84 active components in Jiuwei Jiangtang Oral Liquid were obtained, including 1078 effect targets of active components, 613 targets related to diabetic nephropathy, and 169 intersection targets. The core active components were quercetin, daidzein, puerarin,kaempferol,4′-methoxypuerarin,isorhamnetin, formononetin,β-sitosterol, ellagic acid,geniposide, and calycosin; furthermore, the core targets were GAPDH, tumor necrosis factor (TNF), interleukin (IL)-6, serine/threonine protein kinase (AKT)1, vascular endothelial growth factor A (VEGFA), tumor protein 53 (TP53),and IL-1β. The results of enrichment analyses revealed that the intersection targets were mainly involved in biological processes of responses to hormone, peptide, inorganic substance, nitrogen compound, etc., were enriched in cellular compositions of membrane raft, membrane microdomain, plasma membrane raft, etc., were mainly involved in molecular functions in terms of protein kinase activity, phosphotransferase activity with alcohol as receptor, kinase activity, etc., and were involved in signaling pathways with respect to phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, advanced glycation end-products (AGE)-receptor for advanced glycation end-products (RAGE) signaling pathway in diabetic complications, mitogen-activated protein kinase (MAPK) signaling pathway, hypoxia inducible factor 1 (HIF-1) signaling pathway, TNF signaling pathway, and IL-17 signaling pathway, etc. The results of molecular docking indicated that the docking results of the core active components and the core targets were favorable. ConclusionMultiple active components of Jiuwei Jiangtang Oral Liquid may regulate AGE-RAGE signaling pathway, PI3K/AKT signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, IL-17 signaling pathway, and other signaling pathways, thereby affecting inflammatory responses and oxidative stresses, so as to affect the occurrence and development of diabetic nephropathy through acting on GAPDH, TNF, IL-6, AKT1,VEGFA, TP53, IL-1β, and other targets.

944

浏览量

142

下载量

0

CSCD

工具集