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Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2021 Apr 20;41(2):297–305. doi: 10.1007/s11596-021-2346-x

A Network Pharmacology Study to Uncover the Multiple Molecular Mechanism of the Chinese Patent Medicine Toujiequwen Granules in the Treatment of Corona Virus Disease 2019 (COVID-19)

Bao-yu Yang 1,#, Hao-zhen Wang 1,#, Zhen-zhong Ma 1, Chen Lu 1, Yang Li 1, Zi-yin Lu 1, Xiu-li Lu 1,, Bing Gao 2,
PMCID: PMC8056192  PMID: 33877545

Summary

Since the outbreak of the novel corona virus disease 2019 (COVID-19) at the end of 2019, specific antiviral drugs have been lacking. A Chinese patent medicine Toujiequwen granules has been promoted in the treatment of COVID-19. The present study was designed to reveal the molecular mechanism of Toujiequwen granules against COVID-19. A network pharmacological method was applied to screen the main active ingredients of Toujiequwen granules. Network analysis of 149 active ingredients and 330 drug targets showed the most active ingredient interacting with many drug targets is quercetin. Drug targets most affected by the active ingredients were PTGS2, PTGS1, and DPP4. Drug target disease enrichment analysis showed drug targets were significantly enriched in cardiovascular diseases and digestive tract diseases. An “active ingredient-target-disease” network showed that 57 active ingredients from Toujiequwen granules interacted with 15 key targets of COVID-19. There were 53 ingredients that could act on DPP4, suggesting that DPP4 may become a potential new key target for the treatment of COVID-19. GO analysis results showed that key targets were mainly enriched in the cellular response to lipopolysaccharide, cytokine activity and other functions. KEGG analysis showed they were mainly concentrated in viral protein interaction with cytokine and cytokine receptors and endocrine resistance pathway. The evidence suggests that Toujiequwen granules might play an effective role by improving the symptoms of underlying diseases in patients with COVID-19 and multi-target interventions against multiple signaling pathways related to the pathogenesis of COVID-19.

Key words: Toujiequwen granules, COVID-19, network pharmacology, target, molecular mechanism

Footnotes

The study was supported by the grants from the Education Department of Liaoning Province (No. LFW201701), Liaoning Provincial Key R & D Project (No. 2020JH2/10300114) and Key Laboratory of Shenyang Science and Technology Bureau (No.18-007-0-02).

Conflict of Interest Statement

The authors declare that they have no conflicts of interest.

The authors contributed equally to this study.

Contributor Information

Bao-yu Yang, Email: 928836176@qq.com.

Hao-zhen Wang, Email: wanghzlnu@foxmail.com.

Xiu-li Lu, Email: luxiuli@lnu.edu.cn.

Bing Gao, Email: gaobingdr@hotmail.com.

References

  • 1.Rio CD, Malani PN. 2019 Novel Coronavirus-Important Information for Clinicians. JAMA. 2020;323(11):1039–1040. doi: 10.1001/jama.2020.1490. [DOI] [PubMed] [Google Scholar]
  • 2.Wrapp D, Wang NS, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–1263. doi: 10.1126/science.abb2507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Zumla A, Chan J, Azhar E, et al. Coronaviruses — drug discovery and therapeutic options. Nat Rev Drug Discov. 2016;15(5):327–347. doi: 10.1038/nrd.2015.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Gao Y, Qiu HB, Zhou S, et al. Accumulated Clinical Experiences from Successful Treatment of 1377 Severe and Critically Ill COVID-19 Cases. Curr Med Sci. 2020;40(4):597–601. doi: 10.1007/s11596-020-2221-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Fu X, Lin L, Tan X. Clinical study on 37 case of COVID-19 treated with integrated traditional Chinese and Western Medicine. Zhongyao Xinyao yu Linchuang Yaoli (Chinese) 2020;31(5):600–604. [Google Scholar]
  • 6.Fu X, Lin L, Tan X. Clinical Study on Treatment of Cases of COVID-19 with Toujie Quwen Granules. Zhongguo Shiyan Fangjixue Zazhi (Chinese) 2020;26(12):44–48. [Google Scholar]
  • 7.Sohn EJ, Kim JM, Kang SH, et al. Restoring Effects of Natural Anti-Oxidant Quercetin on Cellular Senescent Human Dermal Fibroblasts. Am J Chinese Med. 2018;46(4):853–873. doi: 10.1142/S0192415X18500453. [DOI] [PubMed] [Google Scholar]
  • 8.Zhang D, Fang J, Chen J, et al. An in vitro study of antihuman cytomegalovirus effect of Forsythia suspensa and its main active ingredient quercetin. Zhongguo Zhongyao Zazhi (Chinese) 2010;35(8):1055–1059. [PubMed] [Google Scholar]
  • 9.Zhang ZM, Guo SJ, Fu SJ, et al. Research Progress of Active Ingredients and Pharmacological Action of Honeysuckle. Animal Husbandry Feed Sci, 2014(1):22–24
  • 10.Sun Y, Xiong YY, Wu HZ, et al. Active Ingredients and Mechanism of Action of Rhizoma Coptidis against Type 2 Diabetes Based on Network-Pharmacology and Bioinformatics. Curr Med Sci. 2020;40(2):257–264. doi: 10.1007/s11596-020-2182-4. [DOI] [PubMed] [Google Scholar]
  • 11.Xiong WC, Wu HZ, Xiong YY, et al. Network Pharmacology-based Research of Active Components of Albiziae Flos and Mechanisms of Its Antidepressant Effect. Curr Med Sci. 2020;40(1):123–129. doi: 10.1007/s11596-020-2155-7. [DOI] [PubMed] [Google Scholar]
  • 12.Hopkins A. Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol. 2008;4(11):682–690. doi: 10.1038/nchembio.118. [DOI] [PubMed] [Google Scholar]
  • 13.Liu XK, Wu JR, Zhang D, et al. A Network Pharmacology Approach to Uncover the Multiple Mechanisms of Willd. on Colorectal Cancer. Evid Based Complement Alternat Med. 2018;2018:1–12. doi: 10.1155/2018/6517034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Liu J, Pei M, Zheng C, et al. A Systems-Pharmacology Analysis of Herbal Medicines Used in Health Improvement Treatment: Predicting Potential New Drugs and Targets. Evid Based Complement Alternat Med. 2013;2013(6):938764. doi: 10.1155/2013/938764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–2504. doi: 10.1101/gr.1239303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Xu Z, Shi L, Wang YJ, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–422. doi: 10.1016/S2213-2600(20)30076-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Yu GC, Wang LG, Han YY, et al. clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters. Omics. 2012;16(5):284–287. doi: 10.1089/omi.2011.0118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Xu H. Research progress of prostaglandin receptors and related drugs. J China Pharm Univ. 2010;41(5):385–394. doi: 10.1002/cjoc.20020200417. [DOI] [Google Scholar]
  • 19.Mcdougall C, Mckay GA, Fisher M. Drugs for diabetes: Part 5 DPP-4 inhibitors. Br J Cardiol. 2011;18(3):130–132. [Google Scholar]
  • 20.Kitano H. Systems Biology: A Brief Overview. Science. 2002;295(5560):1662–1664. doi: 10.1126/science.1069492. [DOI] [PubMed] [Google Scholar]
  • 21.Wang ZP, Xu XJ. scRNA-seq Profiling of Human Testes Reveals the Presence of ACE2 Receptor, a Target for SARS-CoV-2 Infection, in Spermatogonia, Leydig and Sertoli Cells. Cell. 2020;9(4):920. doi: 10.3390/cells9040920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Xiao F, Tang MW, Zheng XB, et al. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020;158(6):1831–1833. doi: 10.1053/j.gastro.2020.02.055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Mao L, Jin HJ, Wang MD, et al. Neurologic Manifestations of Hospitalized Patients with Corona-virus Disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683–690. doi: 10.1001/jamaneurol.2020.1127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Zhi P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–273. doi: 10.1038/s41586-020-2012-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Xu XT, Chen P, Wang JF, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci. 2020;63(3):457–460. doi: 10.1007/s11427-020-1637-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Liu YX, Yang Y, Zhang C, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63(3):364–374. doi: 10.1007/s11427-020-1643-8. [DOI] [PMC free article] [PubMed] [Google Scholar]

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