基于复方网络药理学和分子对接技术研究丹蒌片治疗冠心病的作用机制

Study on Mechanism of Danlou Tablets(丹蒌片)in Treatment of Coronary Heart Disease Based on Compound Network Pharmacology and Molecular Docking Technology

运用网络药理学和分子对接方法探究丹蒌片在冠心病治疗过程中的活性成份以及可能的作用机制,为后续临床试验的广泛靶向代谢组学分析提供参考,为其治疗冠心病提供现代医学理论依据。首先通过TCMSP数据库获取丹蒌片复方中药材有效成份和药物潜在靶点,通过Drugbank和Genecards数据库筛选出冠心病疾病靶点,将筛选出的药物靶点与疾病靶点取交集,获取丹蒌片治疗冠心病的靶点集。通过String数据库对靶点集进行PPI分析,并筛选核心靶基因。基于Metascape数据库对交集基因进行GO功能富集分析及KEGG通路富集分析,最后采用Auto Dock、Pymol软件对丹蒌片关键作用成分与作用靶点进行分子对接验证和可视化处理。结果共筛选得到165个丹蒌片活性成份,344个药物靶点,获得冠心病疾病靶点947个,145个药物与疾病交集基因。通过GO功能富集分析和KEGG通路分析,结果主要涉及AGE-RAGE信号通路、IL-17信号通路、流体剪切应力与动脉粥样硬化、MAPK信号通路、PI3K-Akt信号通路等。分子对接结果显示药物8种关键活性成分与作用靶点受体蛋白对接良好。该研究初步揭示了丹蒌片药物活性成份主要通过抑制调节AGE-RAGE信号通路、IL-17信号通路的表达,可以减少NF-κB的激活,抑制黏附分子、血管内皮生长因子(VEGF)、炎细胞因子等的表达和释放发挥冠心病的治疗作用。

Network pharmacology and molecular docking methods were used to explore the active ingredients and possible mechanisms of Danlou Tablets(丹蒌片)in the treatment of coronary heart disease to provide reference for the extensive targeted metabonomics analysis of subsequent clinical trialsandmodern medicine theoretical basisfor the treatment of coronary heart dis⁃ease.The effective ingredients and potential drug targets of Danlou Tablets were first obtained through the TCMSP database.The coronary heart disease disease targets were screened out through the Drugbank and Genecards databasesand the intersection of the selected drug targets and disease targets were taken to obtain the set of targets of Danlou Tablets for the treatment of coronary heart disease.PPI analysis was performed on the target set through the String database,and core target genes were screened.Based on the Metascape database,the GO function enrichment analysis and KEGG pathway enrichment analysis of the intersection genes were performed.Finally,Auto Dock and Pymol software were used to verify and visualize the molecular docking of the key compo⁃nents and targets of Danlou Tablets.A total of 165 active ingredients of Danlou Tablets,344 drug targets,947 coronary heart dis⁃ease disease targetsand 145 drug-disease intersection genes were screened.Through GO function enrichment analysis and KEGG pathway analysis,the results mainly involved AGE-RAGE signaling pathway,IL-17 signaling pathway,fluid shear stress and atherosclerosis,MAPK signaling pathway,PI3K-Akt signaling pathway,etc.The molecular docking results showed that the eight key active ingredients of the drug docked well with the receptor protein of the target site.The study initially revealed that the ac⁃tive ingredients of Danlou Tablets can reduce the activation of NF-κB,inhibit adhesion molecules,vascular endothelial growth factor(VEGF)and inflammation by inhibiting and regulating the expressions of AGE-RAGE signaling pathway and IL-17 sig⁃naling pathway.The expression and release of cytokines play a role in the treatment of coronary heart disease.