基于网络药理学探讨黄芪太子参药对减轻蒽环类药物心脏毒性的作用机制

The Mechanism of Huangqi (Radix Astragali)-Taizishen (Radix Pseudostellariae) Drug Pair Reducing the Cardiotoxicity of Anthracyclines based on Network Pharmacology

目的基于网络药理学探讨黄芪-太子参药对减轻蒽环类药物心脏毒性的作用机制。方法基于TCMSP数据库、化学专业数据库和PharMapper数据库筛选黄芪-太子参药对的活性成分及其作用靶点。通过GeneCards数据库、OMIM数据库筛选蒽环类药物心脏毒性的疾病靶点。利用Venny 2.1在线分析工具构建韦恩图,获得药物与疾病的共同靶点。应用STRING平台构建共同靶点蛋白质-蛋白质相互作用关系,应用R语言对共同靶点进行GO功能分析和KEGG通路富集分析,通过Cytoscape 3.7.1软件对结果进行可视化呈现。结果预测得到黄芪-太子参药对减轻蒽环类药物心脏毒性主要活性成分21个,药物靶点与疾病靶点的共同靶点39个,槲皮素(度值=32)、木犀草素(度值=17)、山柰酚(度值=12)、金合欢素(度值=7)、β谷固醇(度值=7)是关键活性成分,AKT1、MAPK1、MAPK8、CASP3是关键靶点。GO分析显示,生物过程主要富集在对氧化应激反应、对活性氧的反应、对金属离子反应、凋亡信号通路的调控等;分子功能集中于磷酸酶结合、抗氧化能力、蛋白磷酸酶结合等;细胞组分中涉及膜筏、膜微结构域、膜区域等。KEGG分析显示,共富集到115条信号通路,其中与蒽环类药物心脏毒性相关的通路为PI3K/AKT信号通路、MAPK信号通路、HIF-1信号通路和凋亡信号通路等。结论黄芪-太子参对药可通过抗氧化应激、抗凋亡、调节金属离子代谢等机制减轻蒽环类化疗药物的心脏毒性。

Objective To explore the mechanism of Huangqi(Radix Astragali)-Taizishen(Radix Pseudostellariae) drug pair on reducing the cardiotoxicity of anthracyclines based on network pharmacology. Methods The active ingredients and targets of the herbal pair Huangqi-Taizishen were screened from the TCMSP database, the chemistry database and the PharMapper database. Screen the disease targets of anthracycline cardiotoxicity through GeneCards database and OMIM database. Venny 2.1 online analysis tool was used to construct a Venn diagram to obtain the common target of drugs and disease. The STRING platform was used to construct the protein-protein interaction relationship of the common target. The GO function analysis and the KEGG pathway enrichment analysis of the common target were performed using the R software, and the results were visualized by Cytoscape 3.7.1 software. Results There were 21 main active ingredients of Huangqi-Taizishen on reducing cardiotoxicity of anthracyclines, and 39 common targets of drug targets and disease targets. Quercetin(degree=32), luteolin(degree=17), kaempferol(degree=12), acacetin(degree=7) and β-sitosterol(degree=7) were the key active ingredients, and AKT1, MAPK1, MAPK8 and CASP3 were the key targets. GO analysis showed that biological processes were mainly enriched in responses to oxidative stress, reactive oxygen species, metal ions, and apoptosis signaling pathway etc.;molecular functions were mainly reflected in phosphatase binding, antioxidant capacity, protein phosphatase binding, etc.;cell components were involved with membrane rafts, membrane microstructure domains, membrane regions, etc. KEGG analysis showed that 115 signaling pathways were enriched, and the pathways related to cardiotoxicity of anthracyclines were PI3 K/AKT signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway and apoptosis signaling pathway. Conclusion Huangqi-Taizishen drug pair can reduce the cardiotoxicity of anthracyclines(chemotherapeutics) through anti-oxidative stress, anti-apoptosis, and regulation of metal ion metabolism.