Skip to main content
SpringerLink
Log in

Bencycloquidium bromide inhibits nasal hypersecretion in a rat model of allergic rhinitis

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Object and design

This study is aimed at exploring the effect of Bencycloquidium bromide (BCQB), a novel M1/M3 receptor antagonist, on mucus secretion in a murine model of allergic rhinitis (AR).

Materials and methods

Sprague–Dawley rats were sensitized with ovalbumin to induce AR. After BCQB treatment, nasal symptoms were evaluated. Nasal lavage fluid was used to detect the protein level of cytokines and histamine by the method of enzyme-linked immunosorbent assay. The nasal mucosa of all animals was prepared for western blot, quantitative real-time polymerase chain reaction and histochemical analysis.

Results

BCQB could not only alleviate typical AR symptoms including rhinorrhea, nasal itching and sneezing, but also inhibit the overexpression of mucin 5AC at the level of protein and mRNA. The release of histamine, the mRNA and protein level of IL-6, IL-13 and TNF-α, and the nuclear translocation of NF-κB (p65 and p50) were inhibited by BCQB. In addition, histological studies showed BCQB dramatically inhibited ovalbumin-induced nasal lesions, eosinophil infiltration, aggregation of mast cells, globlet cell hyperplasia and metaplasia.

Conclusions

BCQB attenuates mucus hypersecretion in AR, possibly involving in the NF-κB signaling pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Won Jung H, Jung JK, Weon Cho C, Kang JS, Park YK. Antiallergic effect of KOB03, a polyherbal medicine, on mast cell-mediated allergic responses in ovalbumin-induced allergic rhinitis mouse and human mast cells. J Ethnopharmacol. 2012;142:684–93.

    Article  PubMed  Google Scholar 

  2. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008;63(Suppl 86):8–160.

    Article  PubMed  Google Scholar 

  3. Wang H, Zhang R, Wu J, Hu H. Knockdown of neurokinin-1 receptor expression by small interfering RNA prevents the development of allergic rhinitis in rats. Inflamm Res. 2013;62:903–10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Rogers DF. Airway hypersecretion in allergic rhinitis and asthma: new pharmacotherapy. Curr Allergy Asthma Rep. 2003;3:238–48.

    Article  PubMed  Google Scholar 

  5. Takeuchi K, Yuta A, Sakakura Y. MUC2 mucin gene expression in the nose and maxillary sinus. Am J Otolaryngol. 1995;16:391–5.

    Article  CAS  PubMed  Google Scholar 

  6. Voynow JA, Selby DM, Rose MC. Mucin gene expression (MUC1, MUC2, and MUC5/5AC) in nasal epithelial cells of cystic fibrosis, allergic rhinitis, and normal individuals. Lung. 1998;176:345–54.

    Article  CAS  PubMed  Google Scholar 

  7. Wood SJ, Birchall MA, Carlstedt I, Corfield AP. The expression of MUC5AC in allergic rhinitis. Biochem Soc Trans. 1997;25:504S.

    CAS  PubMed  Google Scholar 

  8. Tai CF, Baraniuk JN. Upper airway neurogenic mechanisms. Curr Opin Allergy Clin Immunol. 2002;2:11–9.

    Article  PubMed  Google Scholar 

  9. Mullol J, Baraniuk JN, Logun C, Merida M, Hausfeld J, Shelhamer JH, et al. M1 and M3 muscarinic antagonists inhibit human nasal glandular secretion in vitro. J Appl Physiol. 1985;1992(73):2069–73.

    Google Scholar 

  10. Ramnarine SI, Haddad EB, Khawaja AM, Mak JC, Rogers DF. On muscarinic control of neurogenic mucus secretion in ferret trachea. J Physiol. 1996;494(Pt 2):577–86.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Nakaya M, Yuasa T, Usui N. Immunohistochemical localization of subtypes of muscarinic receptors in human inferior turbinate mucosa. Ann Otol Rhinol Laryngol. 2002;111:593–7.

    Article  PubMed  Google Scholar 

  12. Cortijo J, Mata M, Milara J, Donet E, Gavalda A, Miralpeix M, et al. Aclidinium inhibits cholinergic and tobacco smoke-induced MUC5AC in human airways. Eur Respir J. 2011;37:244–54.

    Article  CAS  PubMed  Google Scholar 

  13. Bos IS, Gosens R, Zuidhof AB, Schaafsma D, Halayko AJ, Meurs H, et al. Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison. Eur Respir J. 2007;30:653–61.

    Article  CAS  PubMed  Google Scholar 

  14. Bousquet J, Schunemann HJ, Samolinski B, Demoly P, Baena-Cagnani CE, Bachert C, et al. Allergic Rhinitis and its Impact on Asthma (ARIA): achievements in 10 years and future needs. J Allergy Clin Immunol. 2012;130:1049–62.

    Article  CAS  PubMed  Google Scholar 

  15. Bachert C, Vignola AM, Gevaert P, Leynaert B, Van Cauwenberge P, Bousquet J. Allergic rhinitis, rhinosinusitis, and asthma: one airway disease. Immunol Allergy Clin North Am. 2004;24:19–43.

    Article  PubMed  Google Scholar 

  16. Cruz AA, Popov T, Pawankar R, Annesi-Maesano I, Fokkens W, Kemp J, et al. Common characteristics of upper and lower airways in rhinitis and asthma: aRIA update, in collaboration with GA(2)LEN. Allergy. 2007;62(Suppl 84):1–41.

    Article  PubMed  Google Scholar 

  17. Zhou W, Ding L, Wang Y, Sun L, Huang Y, Hu L, et al. Solid phase extraction and liquid chromatography-electrospray ionization-mass spectrometry for the determination of bencycloquidium bromide in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2009;877:897–901.

    Article  CAS  PubMed  Google Scholar 

  18. Jiang B, Ruan Z, Lou H, Dong X, Xie Q. Determination of bencycloquidium bromide in dog plasma by liquid chromatography with electrospray ionization tandem mass spectrometry. Biomed Chromatogr. 2010;24:490–6.

    CAS  PubMed  Google Scholar 

  19. Jiang JX, Cao R, Deng WD, Jin F, Dong XW, Zhu Y, et al. Characterization of bencycloquidium bromide, a novel muscarinic M(3) receptor antagonist in guinea pig airways. Eur J Pharmacol. 2011;655:74–82.

    Article  CAS  PubMed  Google Scholar 

  20. Cao R, Dong XW, Jiang JX, Yan XF, He JS, Deng YM, et al. M(3) muscarinic receptor antagonist bencycloquidium bromide attenuates allergic airway inflammation, hyperresponsiveness and remodeling in mice. Eur J Pharmacol. 2011;655:83–90.

    Article  CAS  PubMed  Google Scholar 

  21. Wen WD, Yuan F, Wang JL, Hou YP. Botulinum toxin therapy in the ovalbumin-sensitized rat. NeuroImmunoModulation. 2007;14:78–83.

    Article  CAS  PubMed  Google Scholar 

  22. Zhu Z, Stone HF, Thach TQ, Garcia L, Ruegg CL. A novel botulinum neurotoxin topical gel: treatment of allergic rhinitis in rats and comparative safety profile. Am J Rhinol Allergy. 2012;26:450–4.

    Article  PubMed  Google Scholar 

  23. Zhao Y, Woo J, Leung P, Chen GG, Wong Y, Liu S, et al. Symptomatic and pathophysiological observations in a modified animal model of allergic rhinitis. Rhinology. 2005;43:47–54.

    CAS  PubMed  Google Scholar 

  24. Wang W, Zheng M. Mucin 5 subtype AC expression and upregulation in the nasal mucosa of allergic rhinitis rats. Otolaryngol Head Neck Surg. 2012;147:1012–9.

    Article  PubMed  Google Scholar 

  25. Oh HA, Kim HM, Jeong HJ. Beneficial effects of chelidonic acid on a model of allergic rhinitis. Int Immunopharmacol. 2011;11:39–45.

    Article  CAS  PubMed  Google Scholar 

  26. Sun L, Ding L, Wang Y, Zhou W, Yan Z, Sun W, et al. Pharmacokinetics, safety and tolerability of Bencycloquidium bromide, a novel selective muscarinic M1/M3 receptor antagonist, after single and multiple intranasal doses in healthy chinese subjects: an open-label, single-center, first-in-human study. Drugs R D. 2012;12:17–28.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Gwilt CR, Donnelly LE, Rogers DF. The non-neuronal cholinergic system in the airways: an unappreciated regulatory role in pulmonary inflammation? Pharmacol Ther. 2007;115:208–22.

    Article  CAS  PubMed  Google Scholar 

  28. Gosens R, Zaagsma J. Grootte Bromhaar M, Nelemans A, Meurs H. Acetylcholine: a novel regulator of airway smooth muscle remodelling? Eur J Pharmacol. 2004;500:193–201.

    Article  CAS  PubMed  Google Scholar 

  29. Howarth PH, Salagean M, Dokic D. Allergic rhinitis: not purely a histamine-related disease. Allergy. 2000;55(Suppl 64):7–16.

    Article  PubMed  Google Scholar 

  30. Wang Z, Li P, Li Y, Zhang Q, Qu Q, Qi Y. A preliminary study on the regulation mechanism of p38MAPK on MUC5AC in allergic rhinitis. J Clin Otorhinolaryngol head Neck surg. 2011;25:943–6.

    CAS  Google Scholar 

  31. Reinheimer T, Baumgartner D, Hohle KD, Racke K, Wessler I. Acetylcholine via muscarinic receptors inhibits histamine release from human isolated bronchi. Am J Respir Crit Care Med. 1997;156:389–95.

    Article  CAS  PubMed  Google Scholar 

  32. Kaliner M, Orange RP, Austen KF. Immunological release of histamine and slow reacting substance of anaphylaxis from human lung. J Exp Med. 1972;136:556–67.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Wang W, Xu X, Zheng M, Wan L. Lipopolysaccharides induces MUC5AC overproduction in human nasal epithelium. Eur Arch Otorhinolaryngol. 2013;270:541–7.

    Article  PubMed  Google Scholar 

  34. Kim YM, Won TB, Kim SW, Min YG, Lee CH, Rhee CS. Histamine induces MUC5AC expression via a hCLCA1 pathway. Pharmacology. 2007;80:219–26.

    Article  CAS  PubMed  Google Scholar 

  35. Whittaker L, Niu N, Temann UA, Stoddard A, Flavell RA, Ray A, et al. Interleukin-13 mediates a fundamental pathway for airway epithelial mucus induced by CD4 T cells and interleukin-9. Am J Respir Cell Mol Biol. 2002;27:593–602.

    Article  CAS  PubMed  Google Scholar 

  36. Smirnova MG, Kiselev SL, Birchall JP, Pearson JP. Up-regulation of mucin secretion in HT29-MTX cells by the pro-inflammatory cytokines tumor necrosis factor-alpha and interleukin-6. Eur Cytokine Netw. 2001;12:119–25.

    CAS  PubMed  Google Scholar 

  37. Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132:344–62.

    Article  CAS  PubMed  Google Scholar 

  38. Fujisawa T, Velichko S, Thai P, Hung LY, Huang F, Wu R. Regulation of airway MUC5AC expression by IL-1beta and IL-17A; the NF-kappaB paradigm. J Immunol. 2009;183:6236–43.

    Article  CAS  PubMed  Google Scholar 

  39. Sheppard KA, Rose DW, Haque ZK, Kurokawa R, McInerney E, Westin S, et al. Transcriptional activation by NF-kappaB requires multiple coactivators. Mol Cell Biol. 1999;19:6367–78.

    PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China in 2012 (No.81200008). We are grateful for the valuable help of professor Li-Ke Xiang of the Department of Pathology, Chongqing Medical University with the histology and immunohistochemistry experiments. We also thank Central Laboratory and Clinical Pharmacology Laboratory of the first Affiliated Hospital of Chongqing Medical University for research help.

Author information

Authors and Affiliations

  1. Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, People’s Republic of China

    Rui Long, Yuanda Zhou, Long Meng, Shenyin Zhu & Juan Li

  2. Department of Oto-Rhino-Laryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Jiangju Huang

  3. Department of Respiratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Li Peng

Authors
  1. Rui Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuanda Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiangju Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Long Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shenyin Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Juan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juan Li.

Additional information

Responsible Editor: Liwu Li.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Long, R., Zhou, Y., Huang, J. et al. Bencycloquidium bromide inhibits nasal hypersecretion in a rat model of allergic rhinitis. Inflamm. Res. 64, 213–223 (2015). https://doi.org/10.1007/s00011-015-0800-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-015-0800-6

Keywords

Search

Navigation