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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

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

Author(s): Ya-Lei Sun, Pei-Pei Zhao, Cheng-Bi Zhu, Xin-Min Li and Bin Yuan*

Volume 27, Issue 7, 2024

Published on: 01 September, 2023

Page: [969 - 983] Pages: 15

DOI: 10.2174/1386207326666230821121358

open access plus

Abstract

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.

Keywords: Qingfei formula, human respiratory syncytial virus pneumonia, network pharmacology, molecular docking simulation, glycoprotein, lung inflammatory injury.

Graphical Abstract
[1]
Bergeron, H.C.; Tripp, R.A. Immunopathology of RSV: An updated review. Viruses, 2021, 13(12), 2478.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1002/cpbi.27]
[9]
Jia, A.; Xu, L.; Wang, Y. Venn diagrams in bioinformatics. Brief. Bioinform., 2021, 22(5), bbab108.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1007/s10753-017-0636-z] [PMID: 28761990]

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