Qingfei Formula Protects against Human Respiratory Syn cytial Virus-induced Lung Inflammatory Injury by Regulating the M APK Signaling Pathway


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Objective:Qingfei formula (QF) is an empirical formula that shows good clinical efficacy in treating human respiratory syncytial virus pneumonia (RSVP). However, the underlying mechanism remains unclear. This study explores the possible pharmacological actions of QF in RSVP treatment.

Methods:We used a network pharmacology approach to identify the active ingredients of QF, forecast possible therapeutic targets, and analyze biological processes and pathways. Molecular docking simulation was used to evaluate the binding capability of active ingredients and therapeutic targets. Finally, in vivo experiments confirmed the reliability of network pharmacology-based prediction of underlying mechanisms.

Results:The study identified 92 potential therapeutic targets and corresponding 131 active ingredients. Enrichment analysis showed that QF downregulated the MAPK signaling pathway and suppressed the inflammatory injury to the lungs induced by the RSV virus. Molecular docking simulations demonstrated that the core active ingredients of QF could stably bind to genes associated with the MAPK signaling pathway. QF had a protective effect against pneumonia in RSV-infected mice. The QF group exhibited a significant reduction in the levels of inflammatory mediators, interleukin- 6 (IL-6), interleukin-8 (CXCL8, IL-8), and P-STAT3, compared to the RSV-induced group. The QF group showed remarkably inhibited MAPK1+3(P-ERK1+2) and MAPK8(P-JNK) protein expression.

Conclusion:The current study showed that QF downregulated the MAPK signaling pathway, which inhibited pulmonary inflammation triggered by RSV infection. This study recommends the appropriate use of QF in the clinical management of RSVP.

Sobre autores

Ya-Lei Sun

Department of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine

Email: info@benthamscience.net

Pei-Pei Zhao

Department of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine

Email: info@benthamscience.net

Cheng-Bi Zhu

Department of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine

Email: info@benthamscience.net

Xin-Min Li

, Henan University of Chinese Medicine

Email: info@benthamscience.net

Bin Yuan

Department of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine

Autor responsável pela correspondência
Email: info@benthamscience.net

Bibliografia

  1. Bergeron, H.C.; Tripp, R.A. Immunopathology of RSV: An updated review. Viruses, 2021, 13(12), 2478. doi: 10.3390/v13122478 PMID: 34960746
  2. Pacheco, G.A.; Gálvez, N.M.S.; Soto, J.A.; Andrade, C.A.; Kalergis, A.M. Bacterial and viral coinfections with the human respiratory syncytial virus. Microorganisms., 2021, 9(6), 1293. doi: 10.3390/microorganisms9061293 PMID: 34199284
  3. Coultas, J.A.; Smyth, R.; Openshaw, P.J. Respiratory syncytial virus (RSV): A scourge from infancy to old age. Thorax., 2019, 74(10), 986-993. doi: 10.1136/thoraxjnl-2018-212212 PMID: 31383776
  4. Zhou, L.H.; Xu, J.Y.; Dai, C.; Fan, Y.M.; Yuan, B. Label-free quantitative proteomics reveals fibrinopeptide B and heparin cofactor II as potential serum biomarkers in respiratory syncytial virus-infected mice treated with Qingfei oral liquid formula. Chin. J. Nat. Med., 2018, 16(4), 241-251. doi: 10.1016/S1875-5364(18)30054-2 PMID: 29703324
  5. Zhang, R.; Zhu, X.; Bai, H.; Ning, K. Network pharmacology databases for traditional chinese medicine: Review and assessment. Front. Pharmacol., 2019, 10, 123. doi: 10.3389/fphar.2019.00123 PMID: 30846939
  6. Jiao, X.; Jin, X.; Ma, Y.; Yang, Y.; Li, J.; Liang, L.; Liu, R.; Li, Z. A comprehensive application: Molecular docking and network pharmacology for the prediction of bioactive constituents and elucidation of mechanisms of action in component-based Chinese medicine. Comput. Biol. Chem., 2021, 90, 107402. doi: 10.1016/j.compbiolchem.2020.107402 PMID: 33338839
  7. Dahary, D.; Golan, Y.; Mazor, Y.; Zelig, O.; Barshir, R.; Twik, M.; Iny Stein, T.; Rosner, G.; Kariv, R.; Chen, F.; Zhang, Q.; Shen, Y.; Safran, M.; Lancet, D.; Fishilevich, S. Genome analysis and knowledge-driven variant interpretation with TGex. BMC Med. Genomics., 2019, 12(1), 200. doi: 10.1186/s12920-019-0647-8 PMID: 31888639
  8. Amberger, J.S.; Hamosh, A. Searching online mendelian inheritance in man (OMIM): A knowledgebase of human genes and genetic phenotypes. Curr. Protoc. Bioinformatics., 2017, 58, 1.2.1-1.2.12. doi: 10.1002/cpbi.27
  9. Jia, A.; Xu, L.; Wang, Y. Venn diagrams in bioinformatics. Brief. Bioinform., 2021, 22(5), bbab108. doi: 10.1093/bib/bbab108 PMID: 33839742
  10. Chen, L.; Zhang, Y.H.; Wang, S.; Zhang, Y.; Huang, T.; Cai, Y.D. Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways. PLoS. One., 2017, 12(9), e0184129. doi: 10.1371/journal.pone.0184129 PMID: 28873455
  11. Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome. Res., 2003, 13(11), 2498-2504. doi: 10.1101/gr.1239303 PMID: 14597658
  12. Szklarczyk, D.; Morris, J.H.; Cook, H.; Kuhn, M.; Wyder, S.; Simonovic, M.; Santos, A.; Doncheva, N.T.; Roth, A.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2017: Quality-controlled protein–protein association networks, made broadly accessible. Nucleic. Acids. Res., 2017, 45(D1), D362-D368. doi: 10.1093/nar/gkw937 PMID: 27924014
  13. Yuan, C.; Wang, M.H.; Wang, F.; Chen, P.Y.; Ke, X.G.; Yu, B.; Yang, Y.F.; You, P.T.; Wu, H.Z. Network pharmacology and molecular docking reveal the mechanism of Scopoletin against non-small cell lung cancer. Life. Sci., 2021, 270, 119105. doi: 10.1016/j.lfs.2021.119105 PMID: 33497736
  14. Dong, W.; Yuan, B.; Zhou, L. Effect of qingfei oral liquid on inflammatory cells and Treg/Th17 expression level in mice infected by respiratory syncytial virus. J. Med. Postg., 2015, 28, 1242-1245.
  15. Shen, C.; Zhang, Z.; Xie, T.; Xu, J.; Yan, J.; Kang, A.; Dai, Q.; Wang, S.; Ji, J.; Shan, J. Jinxin oral liquid inhibits human respiratory syncytial virus-induced excessive inflammation associated with blockade of the NLRP3/ASC/Caspase-1 pathway. Biomed. Pharmacother., 2018, 103, 1376-1383. doi: 10.1016/j.biopha.2018.04.174 PMID: 29864921
  16. Shen, C.; Zhang, Z.; Xie, T.; Ji, J.; Xu, J.; Lin, L.; Yan, J.; Kang, A.; Dai, Q.; Dong, Y.; Shan, J.; Wang, S.; Zhao, X. Rhein suppresses lung inflammatory injury induced by human respiratory syncytial virus through inhibiting NLRP3 inflammasome activation via NF-κB pathway in mice. Front. Pharmacol., 2020, 10, 1600. doi: 10.3389/fphar.2019.01600 PMID: 32047436
  17. Horai, Y.; Kakimoto, T.; Takemoto, K.; Tanaka, M. Quantitative analysis of histopathological findings using image processing software. J. Toxicol. Pathol., 2017, 30(4), 351-358. doi: 10.1293/tox.2017-0031 PMID: 29097847
  18. Freymuth, F.; Brouard, J.; Petitjean, J.; Eugene, G.; Vabret, A.; Duhamel, J.F.; Guillois, B. Virological diagnosis and treatment of respiratory syncytial virus infections. Presse Med., 1994, 23(34), 1571-1576. PMID: 7824493
  19. Lai, Y.; Zhang, Q.; Long, H.; Han, T.; Li, G.; Zhan, S.; Li, Y.; Li, Z.; Jiang, Y.; Liu, X. Ganghuo kanggan decoction in influenza: Integrating network pharmacology and in vivo pharmacological evaluation. Front. Pharmacol., 2020, 11, 607027. doi: 10.3389/fphar.2020.607027 PMID: 33362562
  20. Chen, L.F.; Zhong, Y.L.; Luo, D.; Liu, Z.; Tang, W.; Cheng, W.; Xiong, S.; Li, Y.L.; Li, M.M. Antiviral activity of ethanol extract of Lophatherum gracile against respiratory syncytial virus infection. J. Ethnopharmacol., 2019, 242, 111575. doi: 10.1016/j.jep.2018.10.036 PMID: 30391397
  21. Fonseca, W.; Malinczak, C.A.; Fujimura, K.; Li, D.; McCauley, K.; Li, J.; Best, S.K.K.; Zhu, D.; Rasky, A.J.; Johnson, C.C.; Bermick, J.; Zoratti, E.M.; Ownby, D.; Lynch, S.V.; Lukacs, N.W.; Ptaschinski, C. Maternal gut microbiome regulates immunity to RSV infection in offspring. J. Exp. Med., 2021, 218(11), e20210235. doi: 10.1084/jem.20210235 PMID: 34613328
  22. Han, L.L.; Alexander, J.P.; Anderson, L.J. Respiratory syncytial virus pneumonia among the elderly: An assessment of disease burden. J. Infect. Dis., 1999, 179(1), 25-30. doi: 10.1086/314567 PMID: 9841818
  23. Shang, Z.; Tan, S.; Ma, D. Respiratory syncytial virus: From pathogenesis to potential therapeutic strategies. Int. J. Biol. Sci., 2021, 17(14), 4073-4091. doi: 10.7150/ijbs.64762 PMID: 34671221
  24. Yang, Y.; Wang, S.; Bai, W.; Li, R.; Ai, J. Evaluation by survival analysis on effect of traditional Chinese medicine in treating children with respiratory syncytial viral pneumonia of phlegm-heat blocking Fei syndrome. Chin. J. Integr. Med., 2009, 15(2), 95-100. doi: 10.1007/s11655-009-0095-y PMID: 19407945
  25. Wang, X.; Xie, H.; Xu, S. Meta-analysis of the efficacy and safety of Qingfei Oral Liquid in the treatment of childhood viral pneumonia. Lishizhen. Med. Materia. Medica. Res., 2015, 26, 3054-3058.
  26. Zhang, C.; Yuan, B.; Xu, J. The effect of Qingfei Oral Liquid on the expression of IL-6 and TNF-α in the serum of children with RSV pneumonia. J. Emg. Trad. Chin. Med., 2012, 21, 1216-1217.
  27. Yuan, B.; Wang, A.; Xu, J. The effect of Qingfei oral liquid on the expression levels of serum IL-8 and ICAM-1 in children with respiratory syncytial virus pneumonia. Liaoning. J. Tradit. Chin. Med., 2013, 40, 609-611.
  28. Zhu, Y.; Yuan, B.; Xu, J. From the perspective of TH1/TH2 cell balance to explore the effect of Qingfei Oral Liquid on T-bet and GATA3 levels in RSV infected mice. Liaoning. J. Tradit. Chin. Med., 2014, 41, 805-807.
  29. Shin, J.A.; Oh, S.; Jeong, J.M. The potential of BEN815 as an anti-inflammatory, antiviral and antioxidant agent for the treatment of COVID-19. Phytomed. Plus, 2021, 1(4), 100058. doi: 10.1016/j.phyplu.2021.100058 PMID: 35403084
  30. Kuo, M.Y.; Liao, M.F.; Chen, F.L.; Li, Y.C.; Yang, M.L.; Lin, R.H.; Kuan, Y.H. Luteolin attenuates the pulmonary inflammatory response involves abilities of antioxidation and inhibition of MAPK and NFκB pathways in mice with endotoxin-induced acute lung injury. Food Chem. Toxicol., 2011, 49(10), 2660-2666. doi: 10.1016/j.fct.2011.07.012 PMID: 21782879
  31. Khajuria, V.; Gupta, S.; Sharma, N.; Tiwari, H.; Bhardwaj, S.; Dutt, P.; Satti, N.; Nargotra, A.; Bhagat, A.; Ahmed, Z. Kaempferol-3-o-β- d -glucuronate exhibit potential anti-inflammatory effect in LPS stimulated RAW 264.7 cells and mice model. Int. Immunopharmacol., 2018, 57, 62-71. doi: 10.1016/j.intimp.2018.01.041 PMID: 29475097
  32. Zhou, B.; Li, J.; Liang, X.; Pan, X.; Hao, Y.; Xie, P.; Jiang, H.; Yang, Z.; Zhong, N. β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling. Acta Pharmacol. Sin., 2020, 41(9), 1178-1196. doi: 10.1038/s41401-020-0403-9 PMID: 32504068
  33. Xu, M.; Cao, F.; Zhang, Y.; Shan, L.; Jiang, X.; An, X.; Xu, W.; Liu, X.; Wang, X. Tanshinone IIA therapeutically reduces LPS-induced acute lung injury by inhibiting inflammation and apoptosis in mice. Acta Pharmacol. Sin., 2015, 36(2), 179-187. doi: 10.1038/aps.2014.112 PMID: 25544360
  34. Wang, Y.; Jiang, C.; Shang, Z.; Qiu, G.; Yuan, G.; Xu, K.; Hou, Q.; He, Y.; Liu, Y. AGEs/RAGE promote osteogenic differentiation in rat bone marrow-derived endothelial progenitor cells via MAPK signaling. J. Diabetes Res., 2022, 2022, 1-11. doi: 10.1155/2022/4067812 PMID: 35155684
  35. Cui, X.; Qian, D.W.; Jiang, S.; Shang, E.X.; Zhu, Z.H.; Duan, J.A. Scutellariae radix and coptidis rhizoma improve glucose and lipid metabolism in T2DM rats via regulation of the metabolic profiling and MAPK/PI3K/Akt signaling pathway. Int. J. Mol. Sci., 2018, 19(11), 3634. doi: 10.3390/ijms19113634 PMID: 30453687
  36. Yang, M.; Huang, L.; Li, X.; Kuang, E. Chloroquine inhibits lytic replication of Kaposi’s sarcoma-associated herpesvirus by disrupting mTOR and p38-MAPK activation. Antiviral Res., 2016, 133, 223-233. doi: 10.1016/j.antiviral.2016.08.010 PMID: 27521848
  37. Zhang, X.; Huang, F.; Yang, D.; Peng, T.; Lu, G. Identification of miRNA-mRNA crosstalk in respiratory syncytial virus- (RSV-) associated pediatric pneumonia through integrated miRNAome and transcriptome analysis. Mediators. Inflamm., 2020, 2020, 1-13. doi: 10.1155/2020/8919534 PMID: 32410870
  38. Zhou, M.M.; Zhang, W.Y.; Li, R.J.; Guo, C.; Wei, S.S.; Tian, X.M.; Luo, J.; Kong, L.Y. Anti-inflammatory activity of Khayandirobilide A from Khaya senegalensis via NF-κB, AP-1 and p38 MAPK/Nrf2/HO-1 signaling pathways in lipopolysaccharide-stimulated RAW 264.7 and BV-2 cells. Phytomedicine, 2018, 42, 152-163. doi: 10.1016/j.phymed.2018.03.016 PMID: 29655681
  39. Wang, G.; Xu, B.; Shi, F.; Du, M.; Li, Y.; Yu, T.; Chen, L. Protective effect of methane-rich saline on acetic acid-induced ulcerative colitis via blocking the TLR4/NF- κ B/MAPK pathway and promoting IL-10/JAK1/STAT3-mediated anti-inflammatory response. Oxid. Med. Cell. Longev., 2019, 2019, 1-12. doi: 10.1155/2019/7850324 PMID: 31182999
  40. Bode, J.G.; Ehlting, C.; Häussinger, D. The macrophage response towards LPS and its control through the p38MAPK–STAT3 axis. Cell. Signal., 2012, 24(6), 1185-1194. doi: 10.1016/j.cellsig.2012.01.018 PMID: 22330073
  41. Phuagkhaopong, S.; Ospondpant, D.; Kasemsuk, T.; Sibmooh, N.; Soodvilai, S.; Power, C.; Vivithanaporn, P. Cadmium-induced IL-6 and IL-8 expression and release from astrocytes are mediated by MAPK and NF-κB pathways. Neurotoxicology., 2017, 60, 82-91. doi: 10.1016/j.neuro.2017.03.001 PMID: 28288823
  42. Refsnes, M.; Skuland, T.; Schwarze, P.; Lag, M.; Øvrevik, J. Differential NF-κB and MAPK activation underlies fluoride- and TPA-mediated CXCL8 (IL-8) induction in lung epithelial cells. J. Inflamm. Res., 2014, 7, 169-185. doi: 10.2147/JIR.S69646 PMID: 25540590
  43. Yu, H.H.; Li, M.; Li, Y.B.; Lei, B.B.; Yuan, X.; Xing, X.K.; Xie, Y.F.; Wang, M.; Wang, L.; Yang, H.J.; Feng, Z.W.; Cheng, B.F. Benzoylaconitine inhibits production of IL-6 and IL-8 via MAPK, Akt, NF-κB signaling in IL-1β-induced human synovial cells. Biol. Pharm. Bull., 2020, 43(2), 334-339. doi: 10.1248/bpb.b19-00719 PMID: 31735734
  44. Chen, Y.; Ji, N.; Pan, S.; Zhang, Z.; Wang, R.; Qiu, Y.; Jin, M.; Kong, D. Roburic acid suppresses NO and IL-6 production via targeting NF-κB and MAPK pathway in RAW264.7 cells. Inflammation., 2017, 40(6), 1959-1966. doi: 10.1007/s10753-017-0636-z PMID: 28761990

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