基于网络药理学和分子对接探讨芪丹饮治疗糖尿病肾病作用机制

Discussion on the Mechanism of Qidan Decoction in the Treatment of Diabetic Nephropathy Based on Network Pharmacology and Molecular Docking

目的 运用网络药理学和分子对接技术研究芪丹饮治疗糖尿病肾病的作用机制。方法 在TCMSP数据库筛选芪丹饮有效成分及作用靶点,检索DisGeNET、 DurgBank、 GeneCards、 OMIM、TTD数据库获得糖尿病肾病(DN)靶点;在Venny在线作图工具中将二者映射获取交集靶点。利用Cytoscape3.9.1绘制芪丹饮-有效成分-交集靶点-DN网络,利用STRING平台得到交集靶点蛋白相互作用网络,并在Cytoscape中进行拓扑分析,获得核心靶点,基于DAVID数据库对核心靶点进行GO富集分析和KEGG通路富集分析,最后使用AutoDuck Vina和PyMOL软件进行分子对接验证。结果 获得芪丹饮有效成分125个,治疗DN靶点126个,主要通路有癌症通路、AGE-RAGE、TNF、IL-17、MAPK信号通路。分子对接结果示,度值排名前6位的成分槲皮素、木犀草素、豆甾醇、β-谷甾醇、山柰酚、芒柄花素与AKT1、TNF、IL6、VEGFA、IL1B、TP53对接结合能在-9.2~-6.2 kcal/mol,均具有较强结合力。结论 芪丹饮干预DN可能通过槲皮素、木犀草素、豆甾醇等关键成分,作用于AKT1、TNF、IL6等核心靶点,涉及癌症通路、AGE-RAGE、TNF、IL17、MAPK等信号通路,发挥抗炎、抗氧化、改善血液流变学作用。

Objective To study the mechanism of Qidan Decoction in the treatment of diabetic nephropathy(DN) using network pharmacology and molecular docking technology.Methods The active components and action targets of Qidan Decoction were screened from TCMSP database,and DN targets were obtained by searching DisGeNET,DurgBank,GeneCards,OMIM and TTD databases.Venny online mapping tool was used to map the two to obtain the intersection target.Cytoscape 3.9.1 was used to draw the network diagram of Qidan Decoction-active component-intersection target-DN.The protein interaction network diagram of intersection target was obtained by STRING platform,and the core target was obtained by topology analysis in Cytoscape.GO enrichment analysis and KEGG pathway enrichment analysis were performed for the core targets based on DAVID database.Finally,AutoDuck Vina and PyMOL software were used for molecular docking verification.Results Totally 125 effective components of Qidan Decoction and 126 targets for the treatment of DN were obtained.The main pathways were cancer pathways,AGE-RAGE,TNF,IL-17 and MAPK signaling pathways.The results of molecular docking showed that the binding energies of quercetin,luteolin,stigmasterol,β-sitosterol,kaempferol,and onononetin with AKT1,TNF,IL6,VEGFA,IL1B and TP53 of the top six with the highest degree were between-9.2 and-6.2 kcal/mol,suggesting that they all had strong binding forces.Conclusion Qidan Decoction may interfere with DN through key components such as quercetin,luteolin and legosterol,acting on core targets such as AKT1,TNF and IL6,involving cancer pathway,AGE-RAGE,TNF,IL17 and MAPK signaling pathways,and plays anti-inflammatory,antioxidant and improving hemorheology roles.