藿朴夏苓汤治疗早期新型冠状病毒肺炎(COVID-19)湿邪郁肺证物质基础及功效的网络分析

Analysis on material basis and efficacy network of Huopo Xialing Decoction in treating damp pathogen stagnation of lung syndrome of early COVID-19

目的筛选藿朴夏苓汤治疗早期新型冠状病毒肺炎(COVID-19)湿邪郁肺证的物质基础,预测其作用机制。方法查阅文献及临床报道分析藿朴夏苓汤与早期COVID-19湿邪郁肺证的方证关系。运用TCMSP数据库筛选藿朴夏苓汤中潜在活性成分,将活性成分与新型冠状病毒(SARS-CoV-2)3CL水解酶、血管紧张素转化酶Ⅱ(ACE2)进行分子对接,根据结合能筛选与两者均有较好结合作用的核心成分。借助Cytoscape软件构建关键成分靶点蛋白互作网络,筛选出核心靶点;通过STRING数据库进行核心靶点的GO分析,Cytoscape软件Clue GO插件进行Pathway、KEGG富集分析。结果方证关系分析藿朴夏苓汤用于治疗早期COVID-19湿邪郁肺证,筛选出藿朴夏苓汤中潜在作用成分12个,核心靶点67个。其中通草中的通脱木皂苷元Ⅰ,茯苓、猪苓中的过氧麦角甾醇,半夏中的黄芩苷与SARS-CoV-23CL水解酶、ACE2均具有较好的结合活性。GO、Pathway、KEGG富集分析结果显示藿朴夏苓汤中12个潜在作用成分参与调节刺激反应、信号转导、细胞死亡等生物过程以及白介素信号通路、癌症EGFR信号通路、酪氨酸激酶信号转导途径、编程性细胞死亡途径、MAPK信号通路等。结论藿朴夏苓汤以化湿解毒、宣肺透邪治疗早期COVID-19湿邪郁肺证患者,菲酮、黄芩苷、酸枣仁皂苷、啤酒甾醇、常春藤皂苷元、过氧麦角甾醇、柠檬二烯醇、麦角甾-7,22-二烯-3-酮、通脱木皂苷元Ⅰ、泽泻醇B-23-醋酸酯、泽泻醇B、新橙皮苷可能为其主要的物质基础,通过阻断SARS-CoV-2病毒蛋白合成,阻止病毒进入宿主细胞,通过调控白介素信号通路、MAPK信号通路、PI3K-Akt信号通路、T细胞受体信号通路、C型凝集素受体信号通路,抑制相关炎症因子的表达发挥作用。

Objective To screen the material basis of Huopu Xialing Decoction in the treatment of damp pathogen stagnation of lung syndrome of early COVID-19 and predict its mechanism.Methods Literatures and clinical reports were reviewed to analyze the relationship between Huopu Xialing Decoction and damp pathogen stagnation of lung syndrome of early stage of COVID-19.TCMSP database was used to screen the potential active components in Huopo Xialing Decoction.Molecular docking of the active components with SARS-CoV-2 hydrolase and ACE2 was also carried out.According to the binding ability,the core components with both were screened.The interaction network of key components target proteins was constructed by using the software of Cytoscape to screen the main targets;The GO analysis of the main targets was carried out by using the STRING database,and the Pathway and KEGG enrichment analysis was carried out by using the plug-in of the software ClueGO of Cytoscape.Results The Huopo Xialing Decoction was used to treat the early coronavirus pneumonia with damp pathogen and lung depression syndrome in the relationship analysis between prescriptions and syndrome,and the potential components of the 12 ingredients in Huopo Xialing Decoction were selected,with 67 core targets.Among them,paryriogenin I from Tetrapanax papyrifer,ergosterol peroxide from Poria cocos and Polyporus umbellatus,baicalin from Pinellia ternata had good binding activity with SARS-CoV-23 CL hydrolase and ACE2.The results of enrichment analysis of GO,Pathway and KEGG showed that 12 potential components in Huopo Xialing Decoction were involved in regulating the biological processes such as stimulation response,signal transduction,cell death and the related signaling pathways including interleukins,EGFR in cancer,tyrosine kinases,programmed cell death and MAPK signaling pathways.Conclusion For the early COVID-19 patients with the syndrome of damp pathogen stagnation of lung,Huopo Xialing Decoction was used to resolve dampness and detoxification,and ventilate lung and promote pathogenic penetration.Phenanthrone,baicalin,jujuboside_qt,cerevisterol,hederagenin,ergosterol peroxide,citrostadienol,ergosterol-7,22-diene-3-one,paryriogenin I,alisol B,23-acetate,alisol B,neohesperidin may be the main material basis,and play a role by blocking the protein synthesis of SARS-CoV-2 virus,preventing the virus from entering the host cells,regulating the IL signaling pathway,MAPK signaling pathway,PI3 K-Akt signaling pathway,T cell receptor signaling pathway,C-type lectin receptor signaling pathway and inhibiting the expression of related inflammatory factors.