基于网络药理学的黄连-吴茱萸药对抗癌及治疗心脑血管疾病机制研究

Network pharmacology-based study on mechanisms of drug pair of Coptidis Rhizoma-Euodiae Fructus in treating cancer and cardio-cerebrovascular diseases

目的采用网络药理学阐明黄连-吴茱萸药对多成分、多靶点、多途径的作用特点,为进一步研究黄连-吴茱萸药对抗癌及治疗心脑血管疾病的药效物质基础和机制提供一定理论参考。方法通过TCMSP数据库,以口服生物利用度(OB≥30%)和类药性(DL≥0.18)2个重要参数为依据,经文献整理,结合生物学功能、含量、研究热度等因素筛选黄连-吴茱萸药对活性成分;通过Drugbank和TCMSP数据库进行靶点预测分析;通过Uniprot数据库整理筛选出作用靶点的所有相关基因;结合KEGG数据库进行GO分析和通路分析;使用Cystoscope软件构建化合物-靶点-相关疾病网络图。结果经筛选后得到黄连-吴茱萸药对的41个化合物,212个潜在靶基因,44条主要信号通路,其中30条通路与癌症相关,7条通路与心脑血管疾病有关,7条通路同时参与癌症与心脑血管疾病。结论黄连-吴茱萸药对活性成分通过多成分、多靶点、多通路上调癌症凋亡基因的表达,下调细胞周期与抑凋亡相关基因的表达,而产生抗癌作用;通过抑制血管钙化,保护血管细胞,抑制细胞凋亡与增生达到治疗心脑血管疾病的作用。

Objective To clarify the characteristics of drug pair of Coptidis Rhizoma-Euodiae Fructus on multi-components,multi-targets and multi-pathways based on the network pharmacology,and provide a theoretical reference for further study on the pharmacodynamic basis and mechanism of Coptidis Rhizoma-Euodiae Fructus against cancer and cardio-cerebrovascular diseases.Methods Through the Traditional Chinese Medicine Systems Pharmacology(TCMSP)database,the parameters of oral bioavailability(OB≥30%)and drug-likeness(DL≥0.18)combined with the biological function,contents,research hotspot and other factors were used to screen out the active ingredients of the medicine pair of Coptidis Rhizoma-Euodiae Fructus.DrugBank and TCMSP databases were used to predict and analyze the targets,and Uniprot database was used to sort out all relevant genes affecting the targets.Combining the KEGG database for GO analysis and pathway analysis,"ingredients-targets-related diseases"network was constructed using Cytoscape software.Results A total of 41 compounds and 212 potential target genes,as well as 44 signaling pathways were obtained after screening from Coptidis Rhizoma-Euodiae Fructus,and there were 44 major signaling pathways involved in 30 pathways related to cancer,seven pathways which were related to cardio-cerebrovascular diseases,seven pathways which were related to cancer and cardio-cerebrovascular diseases.Conclusion The active ingredients of Coptidis Rhizoma-Euodiae Fructus can up-regulate the expression of cancer apoptosis genes through multi-components,multi-targets and multi-pathways,down-regulate the expression of cell cycle and apoptosis-related genes,and produce anti-cancer effect;Protecting vascular cells by inhibiting vascular calcification,and to achieve the effect of treating cardio-cerebrovascular diseases by inhibiting apoptosis and proliferation.