天然产物研究与开发 ›› 2020, Vol. 32 ›› Issue (12): 2003-2011.doi: 10.16333/j.1001-6880.2020.12.003

所属专题: No.1

• 专题研究 • 上一篇    下一篇

探析参附注射液治疗新型冠状病毒肺炎合并急性肾损伤的网络药理分子机制

张厦,姜茗宸,陶嘉磊,袁斌*


  

  1. 南京中医药大学附属医院,南京 210029

  • 出版日期:2020-12-28 发布日期:2020-12-24
  • 基金资助:
    国家科技重大专项(2017YFC170201);国家中医药管理局项目(2019XZZX-ek003)

Network pharmacologic molecular mechanism of Shenfu Injection in treatment of COVID-19 with AKI

ZHANG Sha,JIANG Ming-chen,TAO Jia-lei,YUAN Bin*   

  1. Nanjing University of Chinese Medicine,Nanjing 210029,China

  • Online:2020-12-28 Published:2020-12-24

摘要:

本文旨在通过网络药理学和分子对接的方法,解析参附注射液治疗COVID-19合并AKI的作用机制,为中医药治疗COVID-19合并AKI提供理论依据指导,通过 TCMSP数据库获得参附注射液中红参、附子的化学成分并结合文献补充;通过Swiss Target Prediction数据库预测活性化学成分的作用靶点;通过GeneCards数据库筛选COVID-19及合并症AKI的靶点;通过DAVID数据库分别进行GO和KEGG富集分析;运用Cytoscape 3.8.0软件构建中药-成分-靶点-通路网络;AutoDock 4.2.6和PyMol进行核心成分与Mpro、ACE2的分子对接以及可视化处理。结果挖掘出参附注射液中139种活性成分,参附注射液治疗COVID-19及AKI共同靶点共64个,关键靶点涉及TNF、IL6、MAPK3、CASP3等,涉及低氧诱导因子-1 信号通路、肿瘤坏死因子信号通路、PI3K-Akt信号通路、Toll样受体信号通路、细胞凋亡等67条。分子对接结果显示人参皂苷-Rc与ACE2、人参皂苷Rh2与Mpro有较好的结合能力。本研究揭示了参附注射液通过多成分、多靶点、多通路,发挥对抗细胞因子风暴,提高机体免疫,抗氧化应激,减少缺氧-复氧损伤等作用以治疗COVID-19合并AKI的网络药理分子机制。

关键词: 参附注射液, 新型冠状病毒肺炎, 急性肾损伤, 网络药理学, 分子对接

Abstract:

This article aims to analyze the mechanism of Shenfu Injection in the treatment of COVID-19 combined with AKI through network pharmacology and molecular docking methods,and provide theoretical guidance for the treatment of COVID-19 combined with AKI in Chinese medicine.Obtain the chemical composition of red ginseng and aconite in Shenfu Injection through TCMSP database and supplement it with literature;Use the Swiss Target Prediction database to predict the targets of active chemical ingredients;use the GeneCards database to screen the targets of COVID-19 and comorbid AKI;The enrichment analysis of GO and KEGG was carried out through the DAVID database;the Chinese medicine-component-target-channel network was constructed using Cytoscape 3.8.0 software;AutoDock 4.2.6 and PyMol were used for the molecular docking and visualization of the core components with Mpro and ACE2.As a result,139 active ingredients in Shenfu Injection were excavated.There are 64 common targets for Shenfu Injection in the treatment of COVID-19 and AKI.The key targets involve TNF,IL6,MAPK3,CASP3,etc,involving 67 signaling pathways such as hypoxia-inducible factor-1,tumor necrosis factor,PI3K-Akt,Toll-like receptor,and apoptosis.The results of molecular docking showed that ginsenoside-Rc and ACE2,as well as ginsenoside Rh2 and Mpro had better binding ability.This study reveals that Shenfu Injection can treat COVID-19 combined with AKI through multiple components,multiple targets,and multiple pathways to play a role in combating cytokine storm,improving body immunity,resisting oxidative stress and reducing hypoxia-reoxygenation injury.Network pharmacology molecular mechanism.

Key words: Shenfu injection, COVID-19, acute kidney injury, network pharmacology, molecular docking 

中图分类号:  R285