基于网络药理学探讨蔓荆子-连翘抗新型冠状病毒肺炎的作用机制

Mechanism of Fructus Viticis-Fructus Forsythia on COVID-19 based on Network Pharmacology

目的采用网络药理学探讨蔓荆子-连翘的主要化合物和治疗新型冠状病毒肺炎的潜在作用机制。方法利用TCMSP数据库筛选蔓荆子-连翘的主要化合物和作用靶点,通过Cytoscape 3.7.2构建化合物-作用靶点网络图;在GeneC ards数据库中以"Novel Coronavirus"和"Corona Virus Disease"为关键词搜索新型冠状病毒相关疾病靶点,与药物作用靶点取交集筛选共同靶点作为研究靶点,将共同靶点导入STRING数据库获取数据后构建蛋白质-蛋白质相互作用网络图;分析相关靶点的基因功能及代谢通路,预测其作用机制,并构建"成分-靶点-通路"网络图。结果蔓荆子-连翘筛选得到35个化合物,相应作用靶点121个,与新型冠状病毒肺炎的共同靶点28个,涉及关键靶点有TNF、IL6、IL1B等。GO功能富集分析得到生物过程(BP)条目1 122个,细胞组成(CC)条目30个,分子功能(MF)条目33个。KEGG通路富集分析筛选得到111条(P<0.05)信号通路,主要涉及PI3K、TNF、HIF-1、白细胞介素-17(IL-17)信号通路和癌症通路等。结论蔓荆子-连翘中主要化合物槲皮素、木犀草素、山萘酚等能作用于TNF、IL6、PTGS2、PIK3CG、PPARG等靶点调节多条信号通路进行抗炎、抗病毒、调节免疫等作用,从而可能发挥对新型冠状病毒肺炎的治疗作用。

OBJECTIVE To investigate the main compounds of Fructus viticis-Fructus forsythia and the potential mechanism of COVID-19 therapy by network pharmacology. METHODS The main compounds and action targets of Fructus viticis-Fructus forsythia were screened by TCMSP database,and the compound-action target network was constructed by Cytoscape 3. 7. 2. In Genecards database, " Novel Coronavirus" and " Corona Virus Disease" were used as the key words to search for COVID-19 targets,and the intersection with drug action targets was selected to screen common targets as research targets.The common targets were imported into the String database to obtain data,and then the protein-protein interaction network diagram was constructed. The gene functions and metabolic pathways of related targets were analyzed to predict their mechanisms of action,and the " component-target-pathway" network diagram was constructed. RESULTS A total of 35 compounds were identified,121 targets were identified,28 common targets were identified with COVID-19,and TNF,IL6,IL1 B and other key targets were involved.A total of 1 122 items of biological process( BP),30 items of cell composition( CC) and 33 items of molecular function( MF) were obtained by GO functional enrichment analysis.KEGG pathway enrichment analysis screened 111 signaling pathways( P<0.05),mainly involving PI3 K,TNF,HIF-1,interleukin-17( IL-17)signaling pathway and cancer pathways. CONCLUSION The main compounds such as quercetin,luteolin and kaonaphthol in Fructus viticis-Fructus forsythia can act on TNF,IL6,PTGS2,PIK3 CG,PPARG and other targets to regulate multiple signaling pathways to perform anti-inflammatory,antiviral and immunological functions,which may play a therapeutic role on COVID-19.