Skip to main content
PMC home page
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 2020 Dec 22;18(12):941–951. doi: 10.1016/S1875-5364(20)60038-3

Traditional Chinese medicine network pharmacology study on exploring the mechanism of Xuebijing Injection in the treatment of coronavirus disease 2019

Yan XING a, Ying-Rong HUA b, Jing SHANG c, Wei-Hong GE d, Jun LIAO a,*
PMCID: PMC7831566  PMID: 33357725

Abstract

As a representative drug for the treatment of severe community-acquired pneumonia and sepsis, Xuebijing (XBJ) injection is also one of the recommended drugs for the prevention and treatment of coronavirus disease 2019 (COVID-19), but its treatment mechanism for COVID-19 is still unclear. Therefore, this study aims to explore the potential mechanism of XBJ injection in the treatment of COVID-19 employing network pharmacology and molecular docking methods. The corresponding target genes of 45 main active ingredients in XBJ injection and COVID-19 were obtained by using multiple database retrieval and literature mining. 102 overlapping targets of them were screened as the core targets for analysis. Then built the PPI network, TCM-compound-target-disease, and disease-target-pathway networks with the help of Cytoscape 3.6.1 software. After that, utilized DAVID to perform gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to predict the action mechanism of overlapping targets. Finally, by applying molecular docking technology, all compounds were docked with COVID-19 3 CL protease(3CLpro), spike protein (S protein), and angiotensin-converting enzyme II (ACE2). The results indicated that quercetin, luteolin, apigenin and other compounds in XBJ injection could affect TNF, MAPK1, IL6 and other overlapping targets. Meanwhile, anhydrosafflor yellow B (AHSYB), salvianolic acid B (SAB), and rutin could combine with COVID-19 crucial proteins, and then played the role of anti-inflammatory, antiviral and immune response to treat COVID-19. This study revealed the multiple active components, multiple targets, and multiple pathways of XBJ injection in the treatment of COVID-19, which provided a new perspective for the study of the mechanism of traditional Chinese medicine (TCM) in the treatment of COVID-19.

Key words: Network pharmacology, Molecular docking, Xuebijing injection, COVID-19

Footnotes

Available online 20 Dec., 2020

This work was supported by the Double-Class University project (No. CPU2018GY19), the National Natural Science Foundation of China (No. 81874331).

These authors have no conflict of interest to declare.

References

  • 1.Hol TF, Chan KKH, Chung VCH. Highlights of traditional Chinese medicine frontline expert advice in the China national guideline for COVID-19 [J] Eur J Integr Med. 2020 doi: 10.1016/j.eujim.2020.101116. in press. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Wang D, Hu B, Hu C. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. Jama. 2020;323(11):1061–1069. doi: 10.1001/jama.2020.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Chen N, Zhou M, Dong X. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513. doi: 10.1016/s0140-6736(20)30211-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Li Q, Guan X, Wu P. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020;382(13):1199–1207. doi: 10.1056/NEJMoa2001316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Lake MA. What we know so far: COVID-19 current clinical knowledge and research. Clin Med (Lond) 2020;20(2):124–127. doi: 10.7861/clinmed.2019-coron. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Yang Y, Islam MS, Wang J. Traditional Chinese Medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): a review and perspective. Int J Biol Sci. 2020;16(10):1708–1717. doi: 10.7150/ijbs.45538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Shi J, Yang ZG, Ye C. Clinical observation on 49 cases of non-critical COVID-19 in Shanghai treated by integrated traditional Chinese and western medicine. Shanghai J Tradit Chin Med. 2020;54(04):30–35. doi: 10.16305/j.1007-1334.2020.04.095. [DOI] [Google Scholar]
  • 8.Liu S, Yao C, Zhang J. Efficacy of Xuebijing Injection for Sepsis (EXIT-SEP): protocol for a randomised controlled trial. BMJ Open. 2019;9(8) doi: 10.1136/bmjopen-2018-028664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Xu Z, Liu D, Li K. To explore the preventive and therapeutic effects of Xuebijing injection on acute lung injury induced by cardiopulmonary bypass in rats by regulating the expression of microRNA-17-5p and its mechanism. Chin Crit Care Med. 2019;31(7):867–872. doi: 10.3760/cma.j.issn.2095-4352.2019.07.014. [DOI] [PubMed] [Google Scholar]
  • 10.Wang P, Song Y, Liu Z. Xuebijing injection in the treatment of severe pneumonia: study protocol for a randomized controlled trial. Trials. 2016;17(1):142. doi: 10.1186/s13063-016-1282-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Song R, Dong C, Wang C. Effectiveness of Xuebijing in treatment of multiple organ dysfunction syndrome: a Meta analysis. Chin Crit Care Med. 2018;30(9):848–854. doi: 10.3760/cma.j.issn.2095-4352.2018.09.006. [DOI] [PubMed] [Google Scholar]
  • 12.Li T, Qian Y, MIAO Z. Xuebijing Injection alleviates Pam3CSK4-induced inflammatory response and protects mice from sepsis caused by methicillin-resistant staphylococcus aureus. Front Pharmacol. 2020;11:104. doi: 10.3389/fphar.2020.00104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Sun R, Liang M, Yang H. Effect of Xuebijing on inflammatory response and prognosis in patients with septic shock. Chin Crit Care Med. 2020;32(4):458–462. doi: 10.3760/cma.j.cn121430-20200401-00333. [DOI] [PubMed] [Google Scholar]
  • 14.Chen X, Feng Y, Shen X. Anti-sepsis protection of Xuebijing injection is mediated by differential regulation of pro- and anti-inflammatory Th17 and T regulatory cells in a murine model of polymicrobial sepsis. J Ethnopharmacol. 2018;211:358–365. doi: 10.1016/j.jep.2017.10.001. [DOI] [PubMed] [Google Scholar]
  • 15.Zhang Q, Li J, Liang X. The preventive effect of Chinese herbal preparation Xuebijing against hyperactive inflammation after hepato-pancreato-biliary surgery. Ann Transl Med. 2019;7(18):481. doi: 10.21037/atm.2019.07.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Li S, Wang H, Sun Q. Therapeutic effect of Xuebijing, a Traditional Chinese Medicine Injection, on rheumatoid arthritis. Evid Based Comple Alter Med. 2020;2020 doi: 10.1155/2020/2710782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Li CY, Zhang XY, Liu S. Current evidence and researchprospects of Xuebijing Injection in treating novel Coronavirus-infected Pneumonia (COVID-19) World Sci Technol ModTradit Chin Med. 2020;22(2):1–6. [Google Scholar]
  • 18.Guidelines on diagnosis and treatment of novel coronavirus pneumonia (Trial sixth edition) [J] Chin J Infect Control. 2020;19(02):192–195. [Google Scholar]
  • 19.Guidelines on diagnosis and treatment of novel coronavirus pneumonia (Trial fifth edition) [J] Chin J Integr Tradit West Med. 2020;40(02):136–138. [Google Scholar]
  • 20.Zhang CY, Zhang S, Wang W. Clinical observation of Xuebijing in the treatment of COVID-19. Chin J HospPharm. 2020;40(9):964–967. [Google Scholar]
  • 21.Wen L, Zhou Z, Jiang D. Effect of Xuebijing injection on inflammatory markers and disease outcome of coronavirus disease 2019. Chin Crit Care Med. 2020;32(4):426–429. doi: 10.3760/cma.j.cn121430-20200406-00386. [DOI] [PubMed] [Google Scholar]
  • 22.Yuan H, Ma Q, Cui H. How can synergism of traditional medicines benefit from network pharmacology? Molecules. 2017;22(7) doi: 10.3390/molecules22071135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Hopkins AL. 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]
  • 24.Li S, Zhang B. Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin J Nat Med. 2013;11(2):110–120. doi: 10.1016/s1875-5364(13)60037-0. [DOI] [PubMed] [Google Scholar]
  • 25.Huang XF, Cheng WB, Jiang Y. A network pharmacology-based strategy for predicting anti-inflammatory targets of ephedra in treating asthma. Int Immunopharmacol. 2020;83 doi: 10.1016/j.intimp.2020.106423. [DOI] [PubMed] [Google Scholar]
  • 26.Chen J, Wang YK, Gao Y. Protection against COVID-19 injury by qingfei paidu decoction via anti-viral, anti-inflammatory activity and metabolic programming. Biomed Pharmacother. 2020;129 doi: 10.1016/j.biopha.2020.110281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Huang H, Ji L, Song S. Identification of the major constituents in Xuebijing injection by HPLC-ESI-MS. Phytochem Anal. 2011;22(4):330–338. doi: 10.1002/pca.1284. [DOI] [PubMed] [Google Scholar]
  • 28.Sun Z, Zuo L, Sun T. Chemical profiling and quantification of XueBiJing injection, a systematic quality control strategy using UHPLC-Q Exactive hybrid quadrupole-orbitrap high-resolution mass spectrometry. Sci Rep. 2017;7(1) doi: 10.1038/s41598-017-17170-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Tu YR, Ouyang HZ, Sun MJ. Simultaneous identificationof 20 components in Xuebijing injection by UPLC-Q-TOF-MS/MS. J Tianjin Univ Tradit Chin Med. 2017;36(3):209–213. [Google Scholar]
  • 30.Stelzer G, Rosen N, Plaschkes I. The genecards suite: from gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics. 2016;54:1–33. doi: 10.1002/cpbi.5. [DOI] [PubMed] [Google Scholar]
  • 31.Dennis G, Sherman BT, Hosack DA. DAVID bioinformatics resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res. 2007;35(Web Server issue):W169–W175. doi: 10.1093/nar/gkm415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Wrappp D, Wang N, Corbett KS. 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]
  • 33.World Health Organization; 2020. Coronavirus disease (COVID-19) situation report–111 [R] [Google Scholar]
  • 34.Ren JL, Zhang AH, Wang XJ. Traditional Chinese medicine for COVID-19 treatment. Pharmacol Res. 2020;155 doi: 10.1016/j.phrs.2020.104743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Huang C, Wang Y, Li X. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: 10.1016/s0140-6736(20)30183-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Ren Y, Yao MC, Huo XQ. Study on treatment of “cytokine storm” by anti-2019-nCoV prescriptions based on arachidonic acid metabolic pathway. Zhongguo Zhong Yao Za Zhi. 2020;45(6):1225–1231. doi: 10.19540/j.cnki.cjcmm.20200224.405. [DOI] [PubMed] [Google Scholar]
  • 37.Kim J, Woo J, Lyu JH. Carthami Flos suppresses neutrophilic lung inflammation in mice, for which nuclear factor-erythroid 2-related factor-1 is required. Phytomedicine. 2014;21(4):470–478. doi: 10.1016/j.phymed.2013.10.005. [DOI] [PubMed] [Google Scholar]
  • 38.Liu XR, Xu J, Wang YM. The effects of paeoniflorin injection on soluble triggering receptor expressed on myeloid-1 (sTREM-1) levels in severe septic rats. Korean J Physiol Pharmacol. 2016;20(6):565–571. doi: 10.4196/kjpp.2016.20.6.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Chen J, Wang H, Gao C. Tetramethylpyrazine alleviates LPS-induced inflammatory injury in HUVECs by inhibiting Rho/ROCK pathway. Biochem Biophys Res Commun. 2019;514(1):329–335. doi: 10.1016/j.bbrc.2019.04.135. [DOI] [PubMed] [Google Scholar]
  • 40.Zhang Y, Lu W, Zhang X. Cryptotanshinone protects against pulmonary fibrosis through inhibiting Smad and STAT3 signaling pathways. Pharmacol Res. 2019;147 doi: 10.1016/j.phrs.2019.104307. [DOI] [PubMed] [Google Scholar]
  • 41.Liu S, Han Z, Trivett AL. Cryptotanshinone has curative dual anti-proliferative and immunotherapeutic effects on mouse Lewis lung carcinoma. Cancer Immunol Immunother. 2019;68(7):1059–1071. doi: 10.1007/s00262-019-02326-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Bizzarri M, Lagana AS, Aragona D. Inositol and pulmonary function. Could myo-inositol treatment downregulate inflammation and cytokine release syndrome in SARS-CoV-2? Eur Rev Med Pharmacol Sci. 2020;24(6):3426–3432. doi: 10.26355/eurrev_202003_20715. [DOI] [PubMed] [Google Scholar]
  • 43.Zhang Y, Zhong Y, Pan L. Treat 2019 novel coronavirus (COVID-19) with IL-6 inhibitor: Are we already that far? Drug Discov Ther. 2020;14(2):100–102. doi: 10.5582/ddt.2020.03006. [DOI] [PubMed] [Google Scholar]
  • 44.Alijotas-reig J, Esteve-val E, Belizna C. Immunomodulatory therapy for the management of severe COVID-19. Beyond the anti-viral therapy: A comprehensive review [J] Autoimmun Rev. 2020 doi: 10.1016/j.autrev.2020.102569. in press. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Zhu S, Song W, Sun Y, et al. MiR-342 attenuates lipopolysaccharide-induced acute lung injury via inhibiting MAPK1 expression [J]. Clin Exp Pharmacol Physiol, in press. [DOI] [PubMed]
  • 46.Di R, Crisafulli C, Mazzon E. Effect of PD98059, a selective MAPK3/MAPK1 inhibitor, on acute lung injury in mice. Int J Immunopathol Pharmacol. 2009;22(4):937–950. doi: 10.1177/039463200902200409. [DOI] [PubMed] [Google Scholar]
  • 47.Lara PC, Burgos J, Macias D. Low dose lung radiotherapy for COVID-19 pneumonia. The rationale for a cost-effective anti-inflammatory treatment. Clin Transl Radiat Oncol. 2020;23:27–29. doi: 10.1016/j.ctro.2020.04.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Duret PM, Sebbag E, Mallick A. Recovery from COVID-19 in a patient with spondyloarthritis treated with TNF-alpha inhibitor etanercept [J] Ann Rheum Dis, in press. [DOI] [PMC free article] [PubMed]
  • 49.Tursi A, Vetrone LM, Papa A. Anti-TNF-alpha agents in inflammatory bowel disease and course of COVID-19 [J] Inflamm Bowel Dis. 2020 doi: 10.1093/ibd/izaa114. in press. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Chiappelli F, Khakshooy A, Greenberg G. CoViD-19 Immunopathology and Immunotherapy. Bioinformation. 2020;16(3):219–222. doi: 10.6026/97320630016219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Jamilloux Y, Henry T, Belot A. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions [J] Autoimmun Rev. 2020 doi: 10.1016/j.autrev.2020.102567. in press. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Wu D, Yang XO. TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib [J] J Microbiol Immunol Infect. 2020 doi: 10.1016/j.jmii.2020.03.005. S1684-1182(20)30065-7, in press. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020;109 doi: 10.1016/j.jaut.2020.102433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Liu C, Zhou Q, Li Y. Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Cent Sci. 2020;6(3):315–331. doi: 10.1021/acscentsci.0c00272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Wang YP, Guo Y, Wen PS. Three ingredients of safflower alleviate acute lung injury and inhibit NET release induced by lipopolysaccharide. Mediators Inflamm. 2020;2020 doi: 10.1155/2020/2720369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Chung YC, Hsieh FC, Lin YJ. Magnesium lithospermate B and rosmarinic acid, two compounds present in Salvia miltiorrhiza, have potent antiviral activity against enterovirus 71 infections. Eur J Pharmacol. 2015;755:127–133. doi: 10.1016/j.ejphar.2015.02.046. [DOI] [PubMed] [Google Scholar]
  • 57.Lin YJ, Chang YC, Hsiao NW. Fisetin and rutin as 3C protease inhibitors of enterovirus A71. J Virol Methods. 2012;182(1-2):93–98. doi: 10.1016/j.jviromet.2012.03.020. [DOI] [PubMed] [Google Scholar]
  • 58.Bose M, Kamra M, Mullick R. Identification of a flavonoid isolated from plum (Prunus domestica) as a potent inhibitor of Hepatitis C virus entry. Sci Rep. 2017;7(1) doi: 10.1038/s41598-017-04358-5. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Chinese Journal of Natural Medicines are provided here courtesy of Elsevier

RESOURCES