摘要
目的筛选藏药五味沙棘散(WSP)治疗新型冠状病毒肺炎(Corona Virus Disease 2019,COVID-19),的潜在活性成分。方法采用中药系统药理学技术平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)筛选藏药五味沙棘散(沙棘、余甘子、木香、甘草、葡萄)潜在活性成分,采用Swiss Target Prediction预测活性成分的潜在靶点,通过String数据库绘制蛋白质相互作用网络,通过DAVID数据库对WSP作用靶点进行Gene Ontology(GO)功能注释和KEGG通路富集分析,借助Cytoscape 3.7.2构建"药物-成分-靶点"网络。通过Maestro version 11.5软件,将活性成分作为配体与受体血管紧张素转换酶Ⅱ(ACE2)、细胞丝氨酸蛋白酶(TMPRSS2)和COVID-19 3CL水解酶(Mpro)进行分子对接验证。结果 "药物-成分-靶点"网络包含5味药物、29个化合物和32个核心靶点,得到GO功能富集条目225条(p <0.05),KEGG通路富集筛选得到15条信号通路(p <0.05)。分子对接结果显示甘草苷、甘草异黄烷酮、槲皮素、山柰酚等核心化合物与COVID-19靶点结合力最强。结论本研究体现出藏药五味沙棘散"多成分-多靶点-多途径"的作用特点,其活性成分通过与ACE2,TMPRSS2和COVID-19 3CL水解酶结合作用于AKT1、VEGFA、EGFR等靶点,调节MAPK signaling pathway、Toll-like receptor signaling pathway、T cell receptor signaling pathway等多条信号通路,实现对COVID-19肺炎潜在的治疗作用。
Objective To explore the active ingredients of Wuwei Shaji Powder for the treatment of Corona Virus Disease 2019.Methods The potential active ingredients of WSP were screened by TCMSP. The Swiss Target Prediction was used to predict the potential targets of active ingredients, and the protein interaction network was plotted by String database. GO annotation and KEGG pathway enrichment analysis were performed on WSP targets through DAVID database, and the"drug-component-target" network was constructed by means of Cytoscape3.7.2. Meanwhile, the active components were used as ligands to perform molecular docking verification with the receptor angiotensinconverting enzyme II(ACE2), TMPRSS2 and COVID-19 3 CL hydrolase(Mpro) using Maestro version 11.5 software.Results The "Drug-component-target" network includes 5 drugs, 29 compounds and 32 core targets, 225 GO functional enrichment items were obtained(p < 0.05), and 15 signal pathways were obtained through KEGG pathway enrichment and screening(p < 0.05). The results of molecular docking showed that the core compounds such as liquiritigenin, licoisoflavanone, quercetin and kaempferol had the strongest binding force with the target of COVID-19.Conclusion This study reflects the function characteristics of "multi-component-multi-target-multi-pathway" of Tibetan medicine Wuwei Shaji Powder. By combining with ACE2 to act on targets such as AKT1, VEGFA and EGFR,the active compounds of WSP can regulate multiple signaling pathways, which may have therapeutic effects on COVID-19.
作者
刘川
苏锦松
李轩豪
唐策
刘悦
张艺
Liu Chuan;Su Jinsong;Li Xuanhao;Tang Ce;Liu Yue;Zhang Yi(Ethnic Medicine Academic Heritage Innovation Research Center,Chengdu University of Traditional Chinese Medicine,Sichuan,611137,China;Ethnic Medicine College,Chengdu University of Traditional Chinese Medicine,Chengdu,Sichuan,611137,China;Innovation institute of Chinese medicine,Chengdu University of Traditional Chinese Medicine,Chengdu,Sichuan 611137,China;Sichuan Industrial Institute of Antibiotics,Chengdu University,Chengdu 610052.China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2020年第3期632-641,共10页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家重点研发计划项目(2017YFC1703900):民族医药发掘整理与学术传承研究,负责人:张艺
国家自然科学基金委员会项目(81473428):整合EST-SSR分子标记和代谢谱分析的多基原藏药沙棘鉴定与质量控制研究,负责人:张艺
国家自然科学基金委员会项目(81703809):融合体内外分析—靶标网络的藏药“达布班杂”治疗HAPE的药效物质及作用机制研究,负责人:刘悦。
