基于UHPLC-Q-TOF-MS/MS及网络药理学探讨葛根芩连汤治疗代谢综合征的潜在作用机制

Investigation on the Potential Mechanism of Gegen Qinlian Decoction in the Treatment of Metabolic Syndrome Based on UHPLC-Q-TOF-MS/MS and Network Pharmacology

目的基于超高效液相色谱-四级杆飞行时间串联质谱联用技术(UHPLC-Q-TOF-MS/MS)与网络药理学方法探讨葛根芩连汤治疗代谢综合征(Metabolic syndrome,MetS)的潜在作用机制。方法采用UHPLC-QTOF-MS/MS方法分析葛根芩连汤的化学成分;通过Swiss Target Prediction数据库筛选葛根芩连汤中4味中药的成分靶点;通过Genecards、TTD、OMIM数据库检索MetS疾病相关靶点;采用Venny 2.1平台对葛根芩连汤作用靶点与疾病靶点取交集,获得葛根芩连汤治疗MetS的关键靶点;构建“活性成分-靶点”网络及关键靶点蛋白互作(PPI)网络;采用DAVID数据库对关键靶点进行GO功能及KEGG通路富集分析。结果从葛根芩连汤中鉴定出50个化学成分,共筛选出20个关键活性成分,得到葛根芩连汤治疗MetS的关键靶点174个。筛选出SRC、MAPK3、STAT3、HSP90AA1、MAPK8等核心靶点。GO功能富集分析涉及379条生物过程、65条细胞组分和100条分子功能。KEGG通路分析得到Ras信号通路、Rap1信号通路、PI3K-Akt信号通路、VEGF信号通路等108条相关通路。结论明确了葛根芩连汤的化学成分,预测得到葛根芩连汤治疗MetS的药效物质基础及分子机制,可为中药复方研究提供参考。

Objective To investigate the potential mechanism of action of Gegen Qinlian Decoction in the treatment of Metabolic syndrome(MetS) based on ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry(UHPLC-Q-TOF-MS/MS) with a network pharmacology approach. Methods The chemical constituents of Gegen Qinlian Decoction were analyzed by UHPLC-Q-TOF-MS/MS method. The ingredient targets of four Chinese medicines in Gegen Qinlian Decoction were screened by Swiss Target Prediction database;MetS disease-related targets were retrieved by Genecards, TTD and OMIM databases;Venny 2.1 platform was used to obtain the intersection of Gegen Qinlian Decoction action targets and disease targets to obtain the key targets of Gegen Qinlian Decoction for MetS treatment. The “component-target” network and key target protein interaction(PPI) network were constructed;GO function and KEGG pathway enrichment analysis of key targets were performed using DAVID database. Results Fifty chemical components were identified from Gegen Qinlian Decoction,a total of 20 key active components were screened out,and a total of 174 key targets of Gegen Qinlian Decoction for MetS treatment were obtained. Core targets such as SRC,MAPK3,STAT3,HSP90 AA1 and MAPK8 were screened out. GO enrichment analysis involved 379 biological processes,65 cell components and 100 molecular functions. A total of 108 related signaling pathways including Ras, Rap1, PI3K-Akt and VEGF were obtained by KEGG pathway analysis.Conclusion The chemical composition of Gegen Qinlian Decoction was clarified,and the molecular mechanism of the efficacy of Gegen Qinlian Decoction in the treatment of MetS was predicted,which can provide new ideas for the research of Chinese medicine compound.