《中医方剂大辞典》含柴胡防疫组方规律分析及核心药对治疗新型冠状病毒肺炎作用机制研究

Law Analysis of Anti-Epidemic Prescriptions Containing Bupleuri Radix in the Dictionary of Traditional Chinese Medicine Prescriptions and Research on the Mechanism of Core Drug Pair in the Treatment of COVID-19

目的预测柴胡-黄芩药对治疗新型冠状病毒肺炎(COVID-19)的潜在作用靶点及作用机制。方法收集《中医方剂大辞典》中含有柴胡的治疫病方剂,采用SPSS Statistics 25软件对其配伍用药、治疗病症进行频次统计和关联规则、聚类分析等数据挖掘。通过数据库及文献检索并筛选柴胡-黄芩的化学成分和COVID-19的靶点,并通过Cytoscape 3.9.0构建成分-靶标-通路网络。结果收集含柴胡防疫方剂442首,涉及中药334味,用药总频次4877次。网络药理学分析结果显示,柴胡-黄芩活性成分共有靶标80个,治疗COVID-19的主要成分为山柰酚、黄芩素、小檗碱、汉黄芩素、刺槐素等,核心活性基因为表皮生长因子受体(EGFR)、信号转导及转录激活因子3(STAT3)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、白细胞介素2(IL-2)等。基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析得到3736个相关条目和230条信号通路,主要包括EGFR信号通路、缺氧诱导因子1(HIF-1)信号通路、肿瘤坏死因子(TNF)信号通路、血管内皮生长因子(VEGF)信号通路、核因子-κB(NF-κB)信号通路等。结论柴胡-黄芩药对防治COVID-19具有多成分、多靶点、多通路的作用机制,对指导柴胡在中医临床的合理应用、治未病的开发及防疫中药新药研发具有重要意义。

Objective To predict the potential target and mechanism of Bupleuri Radix in the treatment of COVID-19.Methods The anti-epidemic prescriptions containing Bupleuri Radix were collected from the Dictionary of Traditional Chinese Medicine Prescriptions,and the frequency statistics,association rules,cluster analysis,and other data mining on their compatibility and treatment of diseases were conducted by SPSS Statistics 25 software.Chemical components and COVID-19 targets of Bupleuri Radix-Scutellariae Radix were selected through database and literature search,and the"component-target-pathway"network was constructed through Cytoscape 3.9.0.Results A total of 442 anti-epidemic prescriptions containing Bupleuri Radix were collected,involving 334 traditional Chinese medicines(TCM),with a total frequency of 4877 times.The network pharmacological results showed that there were 80 targets for the intersection of the active ingredients of Bupleuri Radix-Scutellariae Radix.The main components of Bupleuri Radix-Scutellariae Radix in the treatment of COVID-19 were kaempferol,baicalin,berberine,wogonin and robinin,and core active genes such as epidermal growth factor receptor(EGFR),signal transduction and transcription activating factor 3(STAT3),serine/threonine protein kinase 1(AKT1),and interleukin-2(IL-2).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis obtained 3736 related items and 230 signaling pathways,mainly including the EGFR signaling pathway,hypoxia-inducible factor-1(HIF-1)signaling pathway,tumor necrosis factor(TNF)signaling pathway,vascular endothelial growth factor(VEGF)signaling pathway,and nuclear factorκB(NF-κB)signal pathways,etc.Conclusion Bupleuri Radix-Scutellariae Radix drug pair has a mechanism of multi-component,multi-target and multi-pathway in the prevention and treatment of COVID-19,which is of great significance for guiding the rational TCM clinical application of Bupleuri Radix,the development of Bupleuri Radix in the disease prevention and treatment,and the research and development of new TCM for epidemic prevention.