参麦注射液治疗新型冠状病毒肺炎(COVID-19)合并冠心病的网络药理分子机制探析

Network pharmacologic molecular mechanism of Shenmai Injection in treatment of COVID-19 combined with coronary heart disease

目的利用网络药理学方法解析参麦注射液治疗新型冠状病毒肺炎(COVID-19)合并冠心病的分子网络作用途径。方法借助中药系统药理学分析平台(TCMSP)和中医百科全书平台(ETCM)收集参麦注射液中红参、麦冬的化学成分;通过SwissTargetPrediction数据库预测化合物的作用靶点;通过NCBI数据库和GeneCards数据库筛选COVID-19及合并症冠心病的靶点;通过DAVID数据库分别进行GO功能富集分析和KEGG通路富集分析;运用Cytoscape 3.7.1软件构建化合物-靶点-通路网络。利用Glide软件对参麦注射液成分与新型冠状病毒(SARS-CoV-2)3CL水解酶(Mpro)的分子对接。结果参麦注射液中麦冬皂苷D′、麦冬皂苷D、人参皂苷Rg2、麦冬甲基黄烷酮A、麦冬苷元-3-O-新橙皮糖苷、人参皂苷Rb2、人参皂苷R0、Ophiopogon A、三七皂苷Rd、麦冬二氢高异黄酮E、人参皂苷Re在分析中显示了较高的度值,且与SARSCoV-23CL水解酶结合力较强,可能是参麦注射液发挥治疗COVID-19合并冠心病的主要药效成分,共涉及到IL6、GAPDH、ALB、TNF、MAPK1、MAPK3、TP53、EGFR、CASP3、CXCL8等77个靶点,以及低氧诱导因子-1信号通路、肿瘤坏死因子信号通路、鞘脂信号通路、Toll样受体信号通路、神经营养素信号通路、血管内皮生长因子信号通路、细胞凋亡、Ras信号通路、PI3K-Akt信号通路、泌乳素信号通路等124条信号通路。结论参麦注射液可能通过抑制细胞因子风暴、维持心脏功能稳态、调节免疫、抗病毒等方面实现对COVID-19与冠心病的同时干预,呈现出了相互影响、复杂关联的网络调控机制。

Objective To analyze the molecular interaction network pathway of Shenmai Injection in the treatment of COVID-19 with coronary heart disease by using network pharmacology.Methods Using the TCMSP and ETCM to retrieve the chemical constituents of Ginseng Radix et Rhizoma Rubra and Ophiopogonis Radix in Shenmai Injection.The target of the compound was predicted through the SwissTargetPrediction database.The target of COVID-19 with coronary heart disease was screened through the NCBI database and the Gene Cards database,and the targets of compound and disease were mapped to obtain the target of the compound for treating the disease.FunRich software and DAVID database were used to perform GO function enrichment analysis and KEGG pathway enrichment analysis,and Excel software and Tableau software to draw bar charts and bubble charts for visualization.Finally,Cytoscape 3.7.1 software was used to build compound-target-pathway network.Glide was used to dock the components of Shenmai Injection with 3 CL hydrolase(Mpro).Results The results showed that ophiopogonin D′,ophiopogonin D,ginsenoside Rg2,methyl ophiopogonanone A,ophiogenin-3-O-α-L-rhamnopyranosyl(1→2)-β-D-glucopyranoside,ginsenoside Rb2,ginsenoside R0,ophiopogon A,sanchinoside Rd,ophiopogonanone E,and ginsenoside Re showed higher degrees in the analysis and stronger binding with 3 CL hydrolase.Those compounds were the main effective components in the treatment of COVID-19 combined with coronary heart disease,involving 77 targets such as IL6,GAPDH,ALB,TNF,MAPK1,MAPK3,TP53,EGFR,CASP3,and CXCL8.KEGG pathway enrichment analysis revealed that there were 124(P<0.05)signaling pathways involving HIF-1 signaling pathway,TNF signaling pathway,sphingolipid signaling pathway,Toll-like receptor signaling pathway,neurotrophin signaling pathway,VEGF signaling pathway,apoptosis,Ras signaling pathway,PI3 K-Akt signaling pathway,and prolactin signaling pathway.The results of molecular docking showed that the affinity between the 17 components of Shenmai Injection and the 3 CL hydrolase of SARS-CoV-2 was less than-25 kJ/mol.Conclusion Shenmai Injection can achieve simultaneous intervention of COVID-19 and coronary heart disease by inhibiting cytokine storms,maintaining cardiac function homeostasis,regulating immunity,and antivirals.It presents the network regulation mechanism of mutual influence and complex correlation.This study can provide a scientific basis for the treatment of Shenmai Injection in critically ill patients with COVID-19.