基于网络药理学和分子对接技术探究苓桂术甘汤干预高血压病和肥胖症“异病同治”作用机制

Study on the molecular mechanism of Linggui Zhugan Decoction in treating hypertension andobesity based on network pharmacology and molecular docking technology

目的运用网络药理学和分子对接技术探究苓桂术甘汤异病同治高血压病和肥胖症的物质基础和作用机制。方法通过TCMSP检索并筛选苓桂术甘汤组方药物的主要有效成分及作用靶点。运用GeneCards、OMIM、TTD、DisGeNET、DrugBank数据库筛选高血压病、肥胖症相关靶点;应用Cytoscape 3.9.0绘制“中药-有效成分-交集靶点-疾病”网络;通过STRING 11.5数据库构建PPI网络;运用cytoNCA插件筛选核心成分及靶点;应用R4.1.2中的Bioconductor程序包进行GO功能及KEGG通路富集分析,并绘制“中药-交集靶点-通路”网络;利用PyMOL、AutoDockTools 1.5.7对活性成分和核心靶点进行分子对接。结果获得苓桂术甘汤潜在有效成分共102个、交集靶点62个,筛选出8个活性成分和7个核心靶点;富集分析显示,关键靶点主要富集在通过流体剪切应力与动脉粥样硬化通、脂质和动脉粥样硬化、AGE-RAGE等信号通路,涉及对营养水平的反应、小分子代谢的调节等生物进程。分子对接显示,结合能<-7 kcal/mol的组合有37组。结论苓桂术甘汤的主要活性成分为槲皮素、山柰酚、柚皮素等,可能通过AKT1、EGFR、IL1B等靶点,作用于流体剪切应力与动脉粥样硬化通路、脂质与动脉粥样硬化通路、AGE-RAGE信号通路发挥作用。

Objective To explore the material basis and mechanism of Linggui Zhugan Decoction in treating hypertension and obesity by means of network pharmacology and molecular docking technique.Methods The TCMSP was retrieved and the main active components and action targets of Linggui Zhugan Decoction were screened.The GeneCards,OMIM,TTD,DisGeNET and DrugBank databases were used to screen disease-related targets of hypertension and obesity. TheCytoscape 3.9.0 was used to draw Chinese materia medica-composition-intersection target-diseasenetwork diagram. The STRING 11.5 database was used to draw PPI network. The cytoNCA plug-inwas used to screen core active components and targets. The bioenrichment analysis of GO and KEGGwas carried out in the R4.1.2, and the Chinese materia medica-intersection target-path diagram wasdrawn, and the core active components and core targets were docked in PyMOL and AutoDockTools1.5.7. Results A total of 102 potentially active components and 62 intersection targets wereobtained, and 8 active components and 7 core targets were screened. Enrichment analysis showedthat the key targets were mainly enriched through the signaling pathways of fluid shear stress andatherosclerosis, lipid and atherosclerosis, and AGE-RAGE, which were involved in biologicalprocesses such as the response to nutritional levels and the regulation of small moleculemetabolism. Molecular docking showed that there were 37 groups with addinity < -7 kcal/mol.Conclusion The main active components of Linggui Zhugan Decoction are quercetin, kaempferoland naringenin, which may play a role in fluid shear stress and atherosclerosis pathway, lipid andatherosclerosis pathway and AGE-RAGE signal pathway through AKT1, EGFR, IL1B and other targets.