摘要
目的运用整合药理学和分子对接探讨辟瘟囊预防新型急状病毒肺炎(COVID-19)的潜在机制。方法利用中医药整合药理学研究平台(TCMIP)分析辟瘟囊预防COVID-19的关键靶点和信号通路,绘制"方剂-中药-疾病-靶标-信号通路"多维网络图,并进行分子对接试验,探讨其临床作用和潜在机制。结果辟瘟囊中具有348个活性成分,1014个药物作用靶点,与COVID-19交集的靶点20个。其中AKT1、HSP90AA1直接参与了"成分-靶标-疾病-信号通路"网络,充当药物成分与疾病信号通路之间的关键靶标。GO功能富集分析结果显示其功能集中在细胞因子介导的信号通路、凋亡过程、信号转导、B细胞增殖等方面。KEGG信号通路集中在白介素系列信号通路,其中白介素-4(IL-4)和白介素-3(IL-13)信号通路的P值最低,与COVID-19的关系最密切,经多维网络图逆向推导结果显示,辟瘟囊中以山柰酚、儿茶素为代表的活性成分作用于HSP90AA1、AKT1,再通过靶标之间相互作用,影响TP53、NFKB1、BCL2,参与IL-4和IL-13信号通路,进而影响COVID-19。分子对接结果显示山柰酚、儿茶素与HSP90AA1、AKT1的结合能低于对照组,可自主结合形成较稳定的结构。结论基于整合药理学研究和分子对接技术分析认为辟瘟囊可经多通路、多靶点发挥对COVID-19的预防作用,推测其主要机制是通过山柰酚、儿茶素作用于HSP90AA1、AKT1靶点,参与IL-4和IL-13信号通路,进而达到预防COVID-19的作用。
Objective To explore the potential mechanism of Biwennang(辟瘟囊) in preventing COVID-19 by integrated pharmacology and molecular docking. Methods TCMIP was used to analyze the key targets and signal pathways of Bi Wen Nang to prevent COVID-19. The multi-dimensional network diagram of " prescription-traditional Chinese medicine-disease-target-signal pathway" was drawn,and molecular docking test was conducted to explore its clinical effect and potential mechanism. Results There were 348 active components,1014 drug targets and 20 cross targets with COVID-19. Among them,AKT1 and HSP90 AA1 are directly involved in the " component-target-disease-signal pathway" network,serving as the key targets between drug components and disease signaling pathways. The results of GO functional enrichment analysis showed that its functions focused on cytokine mediated signal pathway,apoptosis process,signal transduction,B cell proliferation and so on. KEGG signaling pathway is concentrated in the series of interleukin signaling pathways,among which the P value of IL-4 and IL-13 signaling pathways is the lowest,and the relationship between KEGG signaling pathway and COVID-19 is the most close. The results of multi-dimensional network reverse deduction show that kaempferol and catechin act on HAP90 AA1 and AKT1,and then affect TP53,NFKB1,BCL2 through the interaction between targets,and participate in IL-4 and IL-13 signaling pathway,which in turn affects COVID-19. The results of molecular docking showed that kaempferol and catechin could combine with HSP90 AA1 and AKT1 to form stable structures. Conclusion Bi wennang can be used as a preventive and therapeutic measure against COVID-19 through multi-channel and multiple targets based on integrated pharmacology and molecular docking. It is speculated that kaempferol and catechins act on HSP90 AA1 and AKT1 targets,participate in IL-4 and IL-13 signaling pathways,and then prevent COVID-19.
作者
刘德
姚娓
LIU De;YAO Wei(Second Affiliated Hospital of Dalian Medical University,Dalian 116023,Liaoning,China;Institue(College)of Integrative Medicine,DMU,Dalian 116044,Liaoning,China)
出处
《实用中医内科杂志》
2021年第5期1-4,I0001,I0002,共6页
Journal of Practical Traditional Chinese Internal Medicine
基金
国家自然科学基金(81803726)
全国中医临床特色技术传承骨干人才培训项目(国中医药人教函[2019]36)
辽宁省高等学校基本科研项目(LQ2017032)。
