基于网络药理学与分子对接技术探讨糖肾安方治疗糖尿病肾病的作用机制

Study on the Mechanism of Tanshenan Prescription for the Treatment of Diabetic Nephropathy Based on Utilizing Network Pharmacology and Molecular Docking Technology

目的 基于网络药理学和分子对接技术探讨糖肾安方治疗糖尿病肾病的物质基础和作用机制。方法 运用TCMSP检索糖肾安方组方药物的活性成分及对应靶点,检索OMIM、GeneCards、TTD、PharmGKB、DisGeNET数据库获得糖尿病肾病相关靶点,运用Cytoscape3.6.1软件构建“糖肾安方-活性成分-潜在靶点”网络。通过STRING数据库及CytoNCA插件构建糖肾安方治疗糖尿病肾病的蛋白质-蛋白质相互作用网络。采用R语言软件ClusterProfiler、Bioconductor等程序包对潜在靶点进行GO功能和KEGG通路富集分析,并进行分子对接验证。结果 获得糖肾安方治疗糖尿病肾病的核心成分为槲皮素、山柰酚、淫羊藿苷元、豆甾醇,核心作用靶点包括PTGS2、PPARG、JUN、CASP3等。KEGG富集通路包括糖尿病并发症AGE-RAGE信号通路、血脂和动脉粥样硬化相关通路、流体剪切力及动脉硬化通路、炎症与缺氧多条相关通路。分子对接结果显示,糖肾安方活性成分与核心靶点有较好的结合能力。结论 糖肾安方治疗糖尿病肾病的作用机制可能与调控炎症、改善糖基化终产物、减少脂肪堆积、调节葡萄糖稳态等有关。

Objective To explore the mechanism of Tangshenan Prescription for the treatment of diabetic nephropathy(DN)based on network pharmacology and molecular docking technology.Methods The active components and corresponding targets in Tangshenan Prescription was retrieved from TCMSP,and the related target sets of DN were obtained from OMIM,GeneCards,TTD,PharmGKB,DisGeNET databases.Cytoscape 3.6.1 software was used to construct a network of“Tangshenan Prescription-active components-potential targets”.The protein-protein interaction network of Tangshenan Prescription in the treatment of DN was constructed through STRING database and CytoNCA plug-in.ClusterProfiler,Bioconductor and other program packages were used by R language to perform KEGG and GO enrichment analysis.Further verification was carried out by molecular docking.Results The core components of Tangshenan Prescription to treat DN were quercetin,kaempferol,icariin and stigmasterol.The core targets were prostaglandin intraperoxidase synthase(PTGS2),peroxisome proliferation-activated receptorγ(PPARG),transcription factor AP-1(JUN),and cysteinase 3(CASP3).The highly specific pathways included age-rage signaling pathway for diabetic complications,lipid and atherosclerosis related pathways,fluid shear force and atherosclerosis pathway,and inflammation and hypoxia related pathways.The molecular docking results showed that the active components of Tangshenan Prescription had strong binding affinity to the core targets.Conclusion The potential mechanism of Prescriptionin treating diabetes nephropathy may be related to regulating inflammation,improving advanced glycation end products,reducing fat accumulation,and regulating glucose homeostasis.