基于网络药理学研究柴胡达胸合剂治疗新型冠状病毒肺炎的作用机制

The mechanism study on Chaihudaxiong mixture in the treatment of coronavirus disease 2019 with network pharmacology approach

目的基于网络药理学方法探讨柴胡达胸合剂治疗新型冠状病毒肺炎(COVID-19)的潜在药理作用机制。方法利用中药系统药理学数据库和分析平台(TCMSP)筛选柴胡达胸合剂活性成分和对应的作用靶点,并通过Uniprot数据库标准化靶点名称;在GeneCards和OMIM数据库检索冠状病毒相关基因,并与柴胡达胸合剂作用靶点取交集,筛选出治疗作用靶点;利用Cytoscape 3.7.2软件,构建和分析"药材-活性成分-靶点"网络图;通过String平台分析靶点蛋白相互作用,并使用R软件的相关包进行GO基因注释和KEGG信号通路分析。结果筛选出165个有效成分和51个作用靶点,进一步分析发现主要活性成分为β-谷甾醇和11个黄酮类化合物,核心作用靶点为CASP3、MAPK3、IL-6、MAPK8、IL-10、CXCL8、MAPK1、IL-1B等。GO基因注释得到GO条目共1 722个(P<0.05),其中生物学过程条目1 612个,细胞组成条目30个,分子功能条目80个。KEGG信号通路筛选出信号通路156条(P<0.05),富集基因较多的信号通路为糖尿病并发症中的AGE-RAGE信号通路、甲型流感、IL-17信号通路、TNF信号通路和乙型肝炎。结论该研究初步揭示了柴胡达胸合剂多成分、多靶点、多通路对COVID-19发挥治疗作用的特点,为进一步阐明柴胡达胸合剂治疗COVID-19的药理作用机制提供理论依据。

Objective To investigate the pharmacological mechanism of Chaihudaxiong mixture in the treatment of coronavirus disease 2019(COVID-19) based on a network pharmacology approach. Methods The effective ingredients and targets of Chaihudaxiong mixture were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets’ names were standardized by Uniprot database. Genes associated with coronavirus were obtained from the GeneCards and OMIM, which were intersected with effective therapeutic targets. A "herbs-ingredients-targets" network was compiled and analyzed by Cytoscape 3.7.2. The protein-protein interaction of the targets was analyzed by String. The GO gene annotation and KEGG signaling pathway analysis were performed using related packages of the R software. Results A total of165 active ingredients and 51 targets were collected. Further analysis revealed that the main active ingredients were β-sitosterol and11 flavonoids. The core targets were CASP3, MAPK3, IL-6, MAPK8, IL-10, CXCL8, MAPK1 and IL-1 B. A total of 1722 GO entries were obtained from the GO gene annotation(P<0.05), including 1612 entries for biological processes, 30 entries for cell composition, and 80 entries for molecular functions. 156 signaling pathways(P<0.05) were obtained with KEGG signaling pathway screen. The important signaling pathways were AGE-RAGE signaling pathway in diabetic complication, Influenza A, IL-17 signaling pathway, TNF signaling pathway and hepatitis B. Conclusion This study revealed the synergistic features of multicomponent, multi-target, and multi-pathway of Chaihudaxiong mixture in the treatment of COVID-19, which provided an important scientific basis for further understanding the mechanism of Chaihudaxiong mixture in the treatment of COVID-19.