基于网络药理学和分子对接技术分析导痰汤异病同治血管性痴呆和代谢综合征的作用机制

Analysis of Mechanism of Daotan Decoction in Treating Different Diseases with the Same Method for Vascular Dementia and Metabolic Syndrome Based on Network Pharmacology and Molecular Docking Technology

摘要:

目的：运用网络药理学和分子对接技术分析导痰汤异病同治血管性痴呆（VD） 和代谢综合征（MS） 的潜在作用机制。方法：通过TCMSP数据库筛选导痰汤的活性成分及其作用靶点；通过GeneCards、OMIM、TTD和DrugBank数据库获取VD和MS的相关靶点；应用Cytoscape3.9.1软件构建“中药-成分-靶点”网络，绘制“中药-成分-靶点-通路-疾病”复合关联网络；基于STRING平台构建蛋白质相互作用（PPI） 网络，使用CytoNCA筛选核心成分及靶点；Metascape在线分析平台对交集靶点进行基因本体（GO） 功能和京都基因与基因组百科全书（KEGG） 通路富集分析；通过AutoDockTools 1.5.6对核心成分及靶点进行分子对接。结果：获得导痰汤活性成分66种，对应靶点763个，获得VD相关靶点2 613个，MS相关靶点2 415个，药物与疾病共同靶点165个。获得黄芩素、芹菜素、普兰金素、枸橘苷、卡维丁等核心活性成分。获得甘油醛-3-磷酸脱氢酶（GAPDH）、丝氨酸/苏氨酸激酶亚型1（AKT1）、肿瘤蛋白p53（TP53）、白细胞介素-6（IL-6）、肿瘤坏死因子（TNF） 和雌激素受体1（ESR1） 等核心靶点。KEGG通路富集分析主要涉及磷脂酰肌醇（PI3K） /蛋白激酶B（AKT）、糖尿病并发症中的晚期糖基化终末产物及其受体（AGE-RAGE）、胰岛素样生长因子受体等信号通路。核心活性成分与核心靶点的分子对接结合能均＜-5 kcal/mol。结论：导痰汤通过多种药物成分，调节多条信号通路，关联多个关键靶点，发挥对VD和MS的异病同治作用。

Abstract:

Abstract：Objective：To analyze the potential mechanism of Daotan Decoction in treating different diseases with the same method for vascular dementia （VD） and metabolic syndrome （MS） using network pharmacology and molecular docking technology. Methods： The active components and corresponding targets of Daotan Decoction were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） database. Disease targets related to VD and MS were obtained from The Human Gene Database （GeneCards），Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， and DrugBank databases. The "Chinese herbal medicine-component-target" network was constructed using Cytoscape 3.9.1， and a composite "Chinese herbal medicine-component-target-pathway-disease" network was plotted. A protein-protein interaction （PPI） network was built based on the Search Tool for the Retrieval of Interacting Genes/Proteins （STRING） platform，and core components and targets were screened using CytoNCA. Gene Ontology （GO） function and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses of the intersecting targets were performed using the Metascape online platform. Molecular docking of core components and targets was conducted using AutoDockTools 1.5.6. Results：A total of 66 active components of Daotan Decoction were identified，which corresponding to 763 targets. Furthermore，2 613 targets associated with VD and 2 415 targets associated with MS were retrieved， yielding 165 common Chinese herbal medicine-disease targets were identified. The main active components included baicalein， apigenin， prangenin， poncirin， and cavidine. Core targets included glyceral dehyde 3 phosphate dehydrogenase （GAPDH）， AKT serine/ threonine kinase 1 （AKT1）， tumor protein p53 （TP53）， interleukin-6 （IL-6）， tumor necrosis factor （TNF）， and estrogen receptor 1 （ESR1）. KEGG pathway enrichment mainly involved phosphoinostitide 3-kinase （PI3K）/ protein kinase B （AKT） signaling pathway， the advanced glycation end product （AGE）-receptor for AGE （RAGE） signaling pathway in diabetic complications，and insulin-like growth factor receptor signaling pathway and others. The binding affinity of molecular docking between the main active components and core targets was all less than -5 kcal/mol. Conclusion： Daotan Decoction exerts therapeutic effects on VD and MS through multi-component， multi-pathway regulation，association with multiple key targets，and demonstrates treating different diseases with the same method.