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Inhibitory effects and related molecular mechanisms of total flavonoids in Mosla chinensis Maxim against H1N1 influenza virus

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Abstract

Objective

The Shixiangru (Mosla chinensis Maxim) total flavonoids (STF) mainly contain luteolin and apigenin. The study aims to examine the inhibitory effects of STF on anti-H1N1 influenza virus and its related molecular mechanisms in pneumonia mice.

Methods

The viral pneumonia mice were treated with Ribavirin or various doses of STF. We observed histological changes of lung by immunohistochemistry and measured lung index to value anti-influenza virus effects of STF. The concentrations of inflammatory cytokines and anti-oxidant factors were detected by ELISA. RT-PCR and western blot assays were used to determine the expression level of TLR pathway’s key genes and proteins in lung tissues.

Results

We found that the pathological changes of lung in the viral pneumonia mice obviously alleviated by STF treatments and the STF (288 or 576 mg/kg) could significantly decrease lung indices. Moreover, the up-regulation (IL-6, TNF-α, IFN-γ, and NO) and down-regulation (IL-2, SOD and GSH) of inflammatory cytokines and anti-oxidant factors were associated with higher clearance of virus and reduction of inflammatory lung tissue damage. Meanwhile, the expression levels of TLR3, TLR7, MyD88, TRAF3 and NF-κB p65 of the TLR pathway were reduced by STF treatment.

Conclusions

This study suggested that STF may be a promising candidate for treating H1N1 influenza and subsequent viral pneumonia.

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References

  1. Boni MF, de Jong MD, van Doorn HR, Holmes EC. Guidelines for identifying homologous recombination events in influenza A virus. PLoS One. 2010;(5):e10434.

  2. Lin JH, Chiu SC, Lin YC, Cheng JC, Wu HS, Salemi M, Liu HF. Exploring the molecular epidemiology and evolutionary dynamics of influenza A virus in Taiwan. PLoS One. 2013;8(4):e61957.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Seo S, Englund JA, Nguyen JT, Pukrittayakamee S, Lindegardh N, Tarning J, Tambyah PA, Renaud C, Went GT, de Jong MD, Boeckh MJ. Combination therapy with amantadine, oseltamivir and ribavirin for influenza A infection: safety and pharmacokinetics. Antivir Ther. 2013;18(3):377–86.

    Article  CAS  PubMed  Google Scholar 

  4. Li YH, Lin ZF, Zhao MQ, Guo M, Xu TT, Wang CB, Xia HM, Zhu B. Reversal of H1N1 influenza virus-induced apoptosis by silver nanoparticles functionalized with amantadine. Rsc Adv. 2016;6(92):89679–86.

    Article  CAS  Google Scholar 

  5. Karthick V, Ramanathan K. Computational investigation of oseltamivir resistance in influenza A (H5N1) virus. Med Chem Res. 2013;22(12):5764–71.

    Article  CAS  Google Scholar 

  6. Yu CH, Yu WY, Zhong YS, Dai XY, Wu XN, Wu QF. Phytochemical and ethnopharmacological review on Mosla species. Chin Arch Tradit Chin Med. 2013;8:1700–4.

    Google Scholar 

  7. Ge B, Lu XY, Yi K, Jiang HM. Research overview of Mosla chinensis Maxim. Chin Med Mater. 2004;27(4):302–5.

    Google Scholar 

  8. National Pharmacopoeia Committee. Pharmacopoeia of People’s Republic of China. Part 1. Beijing: China Medical Science and Technology Press; 2015. p. 259–60.

    Google Scholar 

  9. Zhang Q, Hao YY, Yu CH, Wu QF. Optimisation for flavonoids extraction from Mosla chinensis Maxim by response surface method. Chi Arch Trad Chin Med. 2012;30(1):116–8.

    Google Scholar 

  10. Yan YF, Chen X, Yang XQ, Wang D, Dong CY, Wu SH. A preliminary study of the active ingredients of volatile oil from Mosla chinensis Maxin. Acta Acad Med QingDao Univ. 2002;38(2):155–7.

    CAS  Google Scholar 

  11. Li M, Miao MS. Characteristic analysis of the Elsholtzia chemistry, pharmacology in clinical application. Chin J Chin Mater Med. 2015;30(4):578–9.

    Google Scholar 

  12. Jiang S, Tang H, Xiao GS. Clinical application study of “Xiangru (Mosla Herb).”. Guid J Tradit Chin Med Pharm. 2015;21(9):95–7.

    CAS  Google Scholar 

  13. Jiang HJ, Lin Y, Chang Q, Wang YZ, Huang ZQ, Liu ZH. Analysis of the contents of total and three major flavonoids in different tissues of Mosla chinensis. Bull Bot Res. 2012;33(2):252–6.

    Google Scholar 

  14. Lee IK, Hwang BS, Kim DW, Kim JY, Woo EE, Lee YJ, Choi HJ, Yun BS. Characterization of neuraminidase inhibitors in Korean papaver Rhoeas bee pollen contributing to anti-influenza activities in vitro. Planta Med. 2016;82(6):524–9.

    Article  CAS  PubMed  Google Scholar 

  15. Liu AL, Liu B, Qin HL, Lee SM, Wang YT, Du GH. Anti-influenza virus activities of flavonoids from the medicinal plant Elsholtzia rugulosa. Planta Med. 2008;74(8):847–51.

    Article  CAS  PubMed  Google Scholar 

  16. Barral PM, Sarkar D, Su ZZ, Barberd GN, DeSallef R, Racanielloe VR, Fisher PB. Functions of the cytoplasmic RNA sensors RIG-I and MDA-5: key regulators of innate immunity. Pharmacol Ther. 2009;124(2):219–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bowie AG, Unterholzner L. Viral evasion and subversion of pattern-recognition receptor signaling. Nat Rev Immunol. 2008;8(12):911–22.

    Article  CAS  PubMed  Google Scholar 

  18. Koyama S, Ishii KJ, Coban C, Akira S. Innate immune response to viral infection. Cytokine. 2008;43(3):336–41.

    Article  CAS  PubMed  Google Scholar 

  19. Zeng YM. Experimental study on anti influenza virus effect and immune regulation mechanism of toxic heat injection. Beijing: Beijing Univ Chin Med. 2009;57–8.

    Google Scholar 

  20. Pan Y. Antagonism effects and signal transduction path of Hao Qin Qing Dan decotion on Damp-heat syndrome of pneumonia disease infected by influenza virus. Guangzhou: Southern Med Univ. 2009;37–8.

    Google Scholar 

  21. Liu R. Study on the anti-influenza virus effect and TLR/IFN signal pathway mechanism of volatile oil of ramulus cinnamomi and cinnamaldehyde. Chengdu: Chengdu Univ Tradit Chin Med. 2012;84–5.

    Google Scholar 

  22. Wu QF, Yu CH, Yan YL, Chen J, Zhang CC, Wen XX. Antiviral flavonoids from Mosla scabra. Fitoterapia. 2010;81(5):429–33.

    Article  CAS  PubMed  Google Scholar 

  23. Yu CH, Yan YL, Wu XN, Zhang B, Wang W, Wu QF. Anti-influenza virus effects of the aqueous extract from Mosla Scabra. J Ethnopharmacol. 2010;127(2):280–5.

    Article  PubMed  Google Scholar 

  24. Wu QF, Wang W, Dai XY, Wang ZY, Shen ZH, Ying HZ, Yu CH. Chemical compositions and anti-influenza activities of essential oils from Mosla dianthera. J Ethnopharmacol. 2012;139(2):668–71.

    Article  CAS  PubMed  Google Scholar 

  25. Zhu WY, Chen WB. Respiratory disease. Beijing: People’s Medical Publishing House; 2003. p. 777–8.

    Google Scholar 

  26. Zhang CH, Zhu D, Liu HG. Research Progress on establishment of experimental animal model of influenza virus infection. J Guangxi Med Univ. 2011;28(5):808–11.

    Google Scholar 

  27. Sun XW, Lv CX, Zhang M, Sun XT, Yu B, Zhang G. Immune protective mechanism of Qingying Jiebiao Heji on influenza. Chin J Exp Tradit Med Form. 2010;16(11):161–4.

    Google Scholar 

  28. Jiang Y, Zhang AQ, Wu CY. Immune mechanism of Shuanghua Baidu decoction on children’s seasonal influenza. J Harbin Med Univ. 2012;46(4):370–5.

    Google Scholar 

  29. Gao RB, Bhatnagar J, Blau DM, Greer P, Rollin DC, Denison AM, Carnes MD, Shieh WJ, Sambhara S, Tumpey TM, Patel M, Liu L, Paddock C, Drew C, Shu YL, Katz JM, Zaki SR. Cytokine and chemokine profiles in lung tissues from fatal cases of 2009 pandemic influenza A (H1N1) role of the host immune response in pathogenesis. Am J Pathol. 2013;183(4):1258–68.

    Article  CAS  PubMed  Google Scholar 

  30. Heltzer ML, Coffin SE, Maurer K, Bagashev A, Zhang Z, Orange JS, Sullivan KE. Immune dysregulation in severe influenza. J Leukoc Biol. 2009;85(6):1036–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kolsuz M, Erginel S, Alataş O, Alataş F, Metintaş M, Uçgun I, Harmanci E, Colak O. Acute phase reactants and cytokine levels in unilateral community-acquired pneumonia. Respiration. 2003;70(6):615–22.

    Article  CAS  PubMed  Google Scholar 

  32. Yang HX. The effect of extract from radix isatidis on influenza virus FM1 strain in vitro and in vivo. Tianjin: Tianjin Med Univ. 2007;41–2.

    Google Scholar 

  33. Vervelde L, Reemers SS, Haarlem DA, Post J, Claassen E, Rebel JMJ, Jansen CA, Vervelde L. Chicken dendritic cells are susceptible to highly pathogenic avian influenzaviruses which induce strong cytokine responses. Dev Comp Immunol. 2013;39(3):198–206.

    Article  CAS  PubMed  Google Scholar 

  34. Sun WM, Wang HQ. Study methodology of cytokines. Beijing: People’s Health Publishing House; 1999. p. 466–86.

  35. Hwang I, Scott JM, Kakarla T, Duriancik DM, Choi S, Cho C, Lee T, Park H, French AR, Beli E, Gardner E, Kim S. Activation mechanisms of natural killer cells during influenza virus infection. PLoS One. 2012;7(12):e51858.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wang CX, Gao GX, Wei SC, Xu HR. The dynamic effect of Yiqi Qingwen Jiedu Heji on the protein expressions of cytokine IFN-γ, TNF-α, IL-10 and IL-6 in the lungs of mice Infected by IV FM1. Chin J Chin Mater Med. 2005;30(7):541–4.

    Google Scholar 

  37. Xu BW. Study on effect and immunological mechanisms of Jiaweixuanfeitoujie decoction on Influenza Viral Pneumonia in mice. Beijing: Beijing Univ Chin Med. 2005;30–1.

    Google Scholar 

  38. Qin S, Mo ZY, Zhao SS, Guan WD, Wang YT, Yang ZF. Inhibitory effect of Baicalin on influenza A virus PR8 strain in vitro. Chin Med Mat. 2012;35(2):280–3.

    CAS  Google Scholar 

  39. Zarubaev VV, Anfimov PM, Shtro AA, Garshinina AV, Meleshkina IA, Karpinskaia LA, Kozeletskaia KN, Kiselev OI. Development of novel drugs against influenza virus based on synthetic and natural compounds. Vopr Viruso. 2012;57(6):30–6.

    CAS  Google Scholar 

  40. Dai JP, Zhao XF, Zeng J, Wan QY, Yang JC, Li WZ, Chen XX, Wang GF, Li KS. Drug screening for autophagy inhibitors based on the dissociation of beclin1–Bcl2 complex using BiFC technique and mechanism of eugenol on anti-influenza A virus activity. PLoS One. 2013;8(4):e61026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Rossella F, Ignacio C, Roberta C, Giuliana CC, Luca P, Leonardo M, Ettore N, Paola C, Anna TP, Lucia N, Roberto DS. Effects of polyphenol compounds on influenza A virus replication and definition of their mechanism of action. Bioorg Med Chem. 2012;20(16):5046–52.

    Article  Google Scholar 

  42. Shen YL. Hydroxyl radical damage to DNA and RNA bases, quantum chemistry research and analysis of electron density topology on reaction mechanism of flavonoids cleaning hydroxyl free radical. Tianjin: Nankai Univ. 2009;8–9.

    Google Scholar 

  43. Du CF. Antioxidant activity mechanism studies on medicinal plants flavones. Zhengzhou: Zhengzhou Univ. 2011;4–6.

    Google Scholar 

  44. Lu XX. Research Progress in Antioxidant Mechanism of Flavnonids. Food Res Dev. 2012;33(3):220–4.

    CAS  Google Scholar 

  45. Akitaka T, Shigeki N, Masafumi S, Kenji F, Naoki L, Yoshifumi L, Taiga M, Koichi L, Hiroshi K, Katsunori Y, Shigeru K. Toll-Like Receptor 4 Agonistic Antibody Promotes Innate Immunity against Severe Pneumonia Induced by Coinfection with Influenza Virus and Streptococcus pneumoniae. Clin Vaccine Immunol. 2013;20(7):977–85.

    Article  Google Scholar 

  46. Gu S, Yin N, Pei JF, Lai LH. Understanding molecular mechanisms of traditional Chinese medicine for the treatment of influenza viruses infection by computational approaches. Mol Biosyst. 2013;9(11):2696–700.

    Article  CAS  PubMed  Google Scholar 

  47. Jin D, Lv FL. Molecular mechanism of TLR3 immune recognition of dsRNA virus. Chin J Virol. 2005;21(2):155–9.

    CAS  Google Scholar 

  48. Shevlin E, Miggin SM. The TIR-Domain Containing Adaptor TRAM Is Required for TLR7 Mediated RANTES Production. PLoS One. 2014;9(9):e107141.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Chang XT, Nian XF, Wang ZH. Progress of research on TLRs-mediated signaling pathway. Prog Physiol Sci. 2011;42(5):340–6.

    CAS  Google Scholar 

  50. Yi Z, Lin WW, Stunz LL, Bishop GA. Roles for TNF-receptor associated factor 3 (TRAF3) in lymphocyte functions. Cytokine Growth F R. 2014;25(2):147–56.

    Article  CAS  Google Scholar 

  51. Zuo WQ, Zhang YC, Gong XH, Zhang YM. Effects of vasoactive intestinal peptide on Toll-like receptor(TLR)2 mRNA and TLR4 mRNA expression on acute lung injury induced by Hpopolysach aride in rat. Chin J Pediatr. 2010;48(1):19–23.

    Google Scholar 

  52. Zhang J, Miao J, Hou J, Lu C. The effects of H3N2 swine influenza virus infection on TLRs and RLRs signaling pathways in porcine alveolar macrophages. Virol J. 2015;12(1):61.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Pattabhi S, Courtney RW, Ran D, Megan LK, Jeffrey P, Shari K, Chad EM, Myra LW, Renee CI, Thomas WG, Kristin MB, Shawn PI, Loo YM, Michael GJ. Targeting innate immunity for antiviral therapy through small molecule agonists of the RLR pathway. J Virol. 2015;90(5):2372.

    Article  PubMed  Google Scholar 

  54. Seo SU, Kwon HJ, Song JH, Byun YH, Seong BL, Kawai T, Akira S, Kweon MN. MyD88 signaling is indispensable for primary influenza A virus infection but dispensable for secondary infection. J Virol. 2010;84(24):12713–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by a Grant from Natural Science Foundation of Zhejiang Province (nos. LY12H27008, LY15H290003 and LY18H280007) and National Natural Science Foundation of China (nos. 81274030/H2803 and 81473335/H2803). Zhejiang Priority Subject (Chinese Pharmacy) Contribution—Open Scientific Research Foundation of Zhejiang Chinese Medical University (Yao2016015). Science Foundation of Zhejiang Chinese Medical University (no. 2015ZR07).

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Correspondence to Qiao-feng Wu.

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Communicated by John Di Battista.

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Zhang, Xx., Wu, Qf., Yan, Yl. et al. Inhibitory effects and related molecular mechanisms of total flavonoids in Mosla chinensis Maxim against H1N1 influenza virus. Inflamm. Res. 67, 179–189 (2018). https://doi.org/10.1007/s00011-017-1109-4

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  • DOI: https://doi.org/10.1007/s00011-017-1109-4

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