Download PDF
Planta Med 2013; 79(03/04): 199-206
DOI: 10.1055/s-0032-1328197
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Effects of Baicalin on Airway Remodeling in Asthmatic Mice

Jing Sun
1   Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China
2   Institute of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China
,
LuLu Li
1   Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China
2   Institute of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China
,
JinFeng Wu
1   Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China
2   Institute of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China
,
BaoJun Liu
1   Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China
2   Institute of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China
,
WeiYi Gong
1   Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China
2   Institute of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China
,
YuBao Lv
1   Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China
2   Institute of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China
,
QingLi Luo
1   Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China
2   Institute of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China
,
XiaoHong Duan
1   Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China
2   Institute of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China
,
JingCheng Dong
1   Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China
2   Institute of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China
› Author Affiliations
Further Information

Publication History

received 15 February 2012
revised 29 December 2012

accepted 09 January 2013

Publication Date:
01 February 2013 (online)

    Permissions and Reprints

Abstract

Airway remodeling is an important characteristic of asthma, linking inflammation with airway hyperresponsiveness. Baicalin, a major active component, was isolated from Radix Scutellariae. Many studies show that baicalin has anti-inflammatory, anti-bacterial, and anti-allergic effects. Here we investigate the influence of baicalin on asthmatic airway remodeling and the mechanism underlining the anti-remodeling effect in vivo.

Asthmatic airway remodeling mice model was established by ovalbumin exposure. Seventy female BALB/c mice were randomly assigned to seven experimental groups: blank, ovalbumin, hexadecadrol, control, and baicalin (25 mg/kg, 50 mg/kg, 100 mg/kg) groups. Pulmonary function was measured using a whole-body plethysmograph in conscious and unrestrained mice. The lung pathology was observed and measured. The production of cytokines in bronchoalveolar lavage fluid and serum was measured using enzyme-labeled immunosorbent assay kits, and the expression levels of transforming growth factor-β 1 and vascular endothelial growth factor were detected by immunohistochemistry. The protein expression levels of transforming growth factor-β 1, vascular endothelial growth factor, extracellular signal–regulated kinase, and p21ras were measured using Western blot. The results show that ovalbumin exposure significantly increased the expression of interleukin-13 in BALF and serum, and transforming growth factor-β 1, vascular endothelial growth factor, extracellular signal–regulated kinase and p21ras expressions in the lungs. Baicalin attenuated the effects of ovalbumin significantly.

It can be concluded that baicalin has significant anti-remodeling effect on ovalbumin-induced asthmatic airway remodeling mice model by decreasing expression of transforming growth factor-β 1, interleukin-13, and vascular endothelial growth factor and inhibiting the activation of the extracellular signal–regulated kinase pathway.

Key words

baicalin - airway remodeling - TGF-β 1 - VEGF - IL-13 - ERK
 

  • References

  • 1 Masoli M, Fabian D, Holt S. The global burden of asthma: executive summary of the GINA dissemination committee report. Allergy 2004; 59: 469-478
    CrossrefPubMedGoogle Scholar
  • 2 Pascual RM, Peters SP. Airway remodeling contributes to the progressive loss of lung function in asthma: An overview. J Allergy Clin Immumol 2005; 116: 477-486
    PubMedGoogle Scholar
  • 3 Halwani R, Al-Muhsen S, Hamid Q. Airway remodeling in asthma. Curr Opin Pharmacol 2010; 10: 236-245
    CrossrefPubMedGoogle Scholar
  • 4 Tang MLK, Wilson JW, Stewart AG, Royce SG. Airway remodeling in asthma: Current understanding and implications for future therapies. Pharmacol Ther 2006; 112: 474-488
    CrossrefPubMedGoogle Scholar
  • 5 Bergeron C, Al-Ramli W, Hamid Q. Remodeling in asthma. Proc Am Thorac Soc 2009; 6: 301-305
    CrossrefPubMedGoogle Scholar
  • 6 Shore SA. Modeling airway remodeling: the winner by a nose?. Am J Respir Crit Care Med 2003; 168: 910-911
    CrossrefPubMedGoogle Scholar
  • 7 Panettieri RA. Airway smooth muscle: an immunomodulatory cell. J Allergy Clin Immunol 2002; 110: 269-274
    CrossrefPubMedGoogle Scholar
  • 8 Tagaya E, Tamaoki J. Mechanisms of airway remodeling in asthma. Allergol Int 2007; 56: 331-340
    CrossrefPubMedGoogle Scholar
  • 9 Homer RJ, Elias JA. Airway remodeling in asthma: therapeutic implications of mechanisms. Physiology 2005; 20: 28-35
    CrossrefPubMedGoogle Scholar
  • 10 Doherty T, Broide D. Cytokines and growth factors in airway remodeling in asthma. Curr Opin Immunol 2007; 19: 676-680
    CrossrefPubMedGoogle Scholar
  • 11 Aili L, Lazaar MD, Reynold A. Molecular mechanisms in allergy and clinical immunology. J Allergy Clin Immunol 2005; 116: 488-495
    CrossrefPubMedGoogle Scholar
  • 12 Jiang B, Zhang SM, Li Q. The significance of baicalin to allergic asthma model. J Pharm Care Res 2001; 1: 36
    PubMedGoogle Scholar
  • 13 Zeng LX, Dong JC, Yu WQ, Huang JH, Liu BJ, Feng XT. Baicalin attenuates inflammation by inhibiting NF-kB activation in cigarette smoke induced inflammatory models. Pulm Pharmacol Ther 2010; 23: 411-419
    CrossrefPubMedGoogle Scholar
  • 14 Kunmr RK, Foster PS. Modeling allergic asthma in mice: pitfalls and opportunities. Am J Respir Cell Mol Biol 2002; 27: 267-272
    CrossrefPubMedGoogle Scholar
  • 15 Pichavant M, Goya S, Hamelmann E, Gelfand EW, Umetsu DT. Animal models of airway sensitization. Curr Prot Immunol 2007; 79: 1-19
    PubMedGoogle Scholar
  • 16 Jeffery PK. Remodeling in asthma and chronic obstructive lung disease. Supplement mechanisms of airway remodeling, from the 16th annual transatlantic airway conference. Am J Respir Crit Care Med 2001; 164: 28-38
    CrossrefPubMedGoogle Scholar
  • 17 Chakir J, Laviolette M, Boutet M, Laliberte R, Dube J, Boulet LP. Lower airways remodeling in nonasthmatic subjects with allergic rhinitis. Lab Invest 1996; 75: 735-744
    PubMedGoogle Scholar
  • 18 Davies DE, Wicks J, Powell RM, Puddicombe SM, Holgate ST. Airway remodeling in asthma: new insights. J Allergy Clin Immunol 2003; 111: 215-225
    CrossrefPubMedGoogle Scholar
  • 19 Kelly MM, OʼConnor TM, Leigh R, Otis J, Gwozd C, Gauvreau GM, Gauldie J, OʼByrne PM. Effects of budesonide and formoterol on allergen-induced airway responses, inflammation, and airway remodeling in asthma. J Allergy Clin Immunol 2010; 125: 349-356
    CrossrefPubMedGoogle Scholar
  • 20 Henderson WR, Chiang GK, Tien Y, Chi EY. Reversal of allergen-induced airway remodeling by CysLT1 receptor blockade. Am J Respir Crit Care Med 2006; 173: 718-728
    CrossrefPubMedGoogle Scholar
  • 21 Bates JH, Rincon M, Irvin CG. Animal models of asthma. Am J Physiol Lung Cell Mol Physiol 2009; 297: 401-410
    CrossrefPubMedGoogle Scholar
  • 22 Ramos-Barbón D, Ludwig MS, Martin JG. Airway remodeling: lessons from animal models. Clin Rev Allergy Immunol 2004; 27: 3-21
    CrossrefPubMedGoogle Scholar
  • 23 Hirota JA, Hackett TL, Inman MD, Knight DA. Modeling asthma in mice: what have we learned about the airway epithelium?. Am J Respir Cell Mol Biol 2011; 44: 431-438
    CrossrefPubMedGoogle Scholar
  • 24 Michalik M, Pierzchalska M, Legutko A, Ura M, Ostaszewska A, Soja J, Sanak M. Asthmatic bronchial fibroblasts demonstrate enhanced potential to differentiate into myofibroblasts in culture. Med Sci Monit 2009; 15: 194-201
    PubMedGoogle Scholar
  • 25 Ito I, Fixman ED, Asai K. Platelet-derived growth factor and transforming growth factor-beta modulate the expression of matrix metalloproteinases and migratory function of human airway smooth muscle cells. Clin Exp Allergy 2009; 39: 1370-1380
    CrossrefPubMedGoogle Scholar
  • 26 Murphy DM, OʼByrne PM. Recent advances in the pathophysiology of asthma. Chest 2010; 137: 1417-1426
    CrossrefPubMedGoogle Scholar
  • 27 McGee HS, Agrawal DK. TH2 cells in the pathogenesis of airway remodeling: regulatory T cells a plausible panacea for asthma. Immunol Res 2006; 35: 219-232
    CrossrefPubMedGoogle Scholar
  • 28 Hoshino M, Takahashi M, Aoike N. Expression of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin immunoreactivity in asthmatic airways and its relationship to angiogenesis. J Allergy Clin Immunol 2001; 107: 295-301
    CrossrefPubMedGoogle Scholar
  • 29 Lee CG, Link H, Baluk P, Homer RJ, Chapoval S, Bhandari V, Kang MJ, Cohn L, Kim YK, Mcdonald DM, Elias JA. Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung. Nat Med 2004; 10: 1095-1103
    CrossrefPubMedGoogle Scholar
  • 30 Hirst SJ, Martin JG, Bonacci JV, Chan V, Fixman ED, Hamid QA, Herszberg B, Lavoie JP, Mcvicker CG, Moir LM, Nguyen TT, Peng Q, Barbon DR, Stewart AG. Proliferative aspects of airway smooth muscle. J Allergy Clin Immunol 2004; 114: 2-17
    PubMedGoogle Scholar