Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
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Anti-inflammatory Effects and its Mechanisms of Hesperidin in an Asthmatic Mouse Model Induced by Ovalbumin

  • Chang, Jeong-Hyun (Department of Clinical Laboratory Science, College of Health & Therapy, Daegu Haany University)
  • Received : 2010.05.25
  • Accepted : 2010.06.08
  • Published : 2010.06.30
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Abstract

Hesperidin, a member of the flavanone group of flavonoids, can be isolated in large amounts from the rinds of some citrus species [e.g., Citrus aurantium L. (bitter orange), Citrus sinensis L. (sweet orange) and Citrus unshiu Marcov. (satsuma mandarin)], and has been reported to have anticarcinogenic, antihypotensive and antimicrobial properties. Despite the efficacy of these polyphenolic compounds as immune modulators, the effects of the flavonoids are poorly understood about allergic effect. In this study, we investigated whether hesperidin could influence on Th1 and Th2 balance. Allergic reactions included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, airway luminal narrowing, the development of airway hyper-responsiveness (AHR). The administration of hesperidin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that hesperidin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of hesperidin in terms of its effects in a murine model of asthma, and also broaden current perspectives in our understanding of the immunopharmacological functions of hesperidin.

Keywords

References

  1. Bahar-Shany K, Ravid A, Koren R. Upregulation of MMP-9 production by TNFalpha in keratinocytes and its attenuation by vitamin D. J Cell Physiol. 2010. 222: 729-737.
  2. Boschetto P, Fabbri LM, Zocca E, Milani G, Pivirotto F, Dal Vecchio A, Plebani M, Mapp CE. Prednisone inhibits late asthmatic reactions and airway inflammation induced by toluene diisocyanate in sensitized subjects. J Allergy Clin Immunol. 1988. 81: 454. https://doi.org/10.1016/0091-6749(88)90916-5
  3. Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P. Eosinophilic inflammation in asthma. N Engl J Med. 1990. 323: 1033-1039. https://doi.org/10.1056/NEJM199010113231505
  4. Busse WW, William FC, Sedgwick JD. Mechanism of airway inflammation in asthma. Am Rev Respir Dis. 1993. 147: 20 -24. https://doi.org/10.1164/ajrccm/147.6_Pt_2.S20
  5. Chen CC, Chow MP, Huang WC, Lin YC, Chang YJ. Flavonoids inhibit tumor necrosis factor-alpha-induced up-regulation of intercellular adhesion molecule-1 (ICAM-1) in respiratory epithelial cells through activator protein-1 and nuclear factorkappaB: tructure-activity relationships. Mol Pharmacol. 2004. 66: 683-693.
  6. Choi JR, Lee CM, Jung ID, Lee JS, Jeong YI, Chang JH, Park HJ, Choi IW, Kim JS, Shin YK, Park SN, Park YM. Apigenin protects ovalbumin-induced asthma through the regulation of GATA-3 gene. Int Immunopharmacol. 2009. 9: 918-924. https://doi.org/10.1016/j.intimp.2009.03.018
  7. Corrigan CJ, Kay AB. T cells and eosinophils in the pathogenesis of asthma. Immunol Today 1992. 13: 501-507. https://doi.org/10.1016/0167-5699(92)90026-4
  8. Garg A, Garg S, Zaneveld LJ, Singla AK. Chemistry and pharmacology of the citrus bioflavonoid hesperidin. Phytother Res. 2001. 15: 655-669. https://doi.org/10.1002/ptr.1074
  9. Gleich GJ, Kita H. Bronchial asthma: lessons from murine models. Proc Natl Acad Sci U S A. 1997. 94: 2101-2102. https://doi.org/10.1073/pnas.94.6.2101
  10. Hamelmann E, Schwarze J, Takeda K, Oshiba A, Larsen GL, Irvin CG, Gelfand EW. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med. 1997. 156: 766-775. https://doi.org/10.1164/ajrccm.156.3.9606031
  11. Heidenfelder B, Johnson M, Hudgens E, Inmon J, Hamilton RG, Neas L, Gallagher JE. Increased plasma reactive oxidant levels and their relationship to blood cells, total IgE, and allergen-specific IgE levels in asthmatic children. J Asthma 2009. 46: 687-691. https://doi.org/10.1080/02770900903056179
  12. Iwamoto I, Nakajima H, Endo H, Yoshida S. Interferon gamma regulates antigen induced eosinophil recruitment into the mouse airways by inhibiting the infiltration of CD4+ T cells. J Exp Med. 1993. 177: 573-576. https://doi.org/10.1084/jem.177.2.573
  13. Kay AB. Asthma and inflammation. J Allergy Clin Immunol. 1991. 87: 893-910. https://doi.org/10.1016/0091-6749(91)90408-G
  14. Kwak YG, Song CH, Yi HK, Hwang PH, Kim JS, Lee KS, Lee YC. Involvement of PTEN in airway hyper-responsiveness and inflammation in bronchial asthma. J Clin Invest. 2003. 111: 1083-1092.
  15. Lee CM, Chang JH, Moon DO, Choi YH, Choi IW, Park YM, Kim GY. Lycopene suppresses ovalbumin-induced airway inflammation in a murine model of asthma. Biochem Biophys Res Commun. 2008. 374: 248-252. https://doi.org/10.1016/j.bbrc.2008.07.032
  16. Lee YC, Kwak YG, Song CH. Contribution of vascular endothelial growth factor to airway hyper-responsiveness and inflammation in a murine model of toluene diisocyanateinduced asthma. J Immunol. 2002. 168: 3595-3600.
  17. Lu Y, Sjostrand M, Malmhall C, Radinger M, Jeurink P, Lotvall J, Bossios A. New production of eosinophils and the corresponding TH1/TH2 balance in the lungs after allergen exposure in BALB/c and C57BL/6 mice. Scand J Immunol. 2010. 71: 176-185. https://doi.org/10.1111/j.1365-3083.2009.02363.x
  18. Mappe CE, Boschetto P, Zocca E, Milani GF, Pivirotto F, Teggazin V, Fabbri LM. Pathogenesis of late asthmatic reactions induced by exposure to isocyanates. Bull Eur Physiopathol Respir. 1987. 23: 583-586.
  19. Muller WA. Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol. 2003. 24: 327-334.
  20. Park CS, Kim TB, Lee KY, Moon KA, Bae YJ, Jang MK, Cho YS, Moon HB. Increased oxidative stress in the airway and development of allergic inflammation in a mouse model of asthma. Ann Allergy Asthma Immunol. 2009. 103: 238-247. https://doi.org/10.1016/S1081-1206(10)60188-3
  21. Perez-Gracia JL, Prior C, Guillén-Grima F, Segura V, Gonzalez A, Panizo A, Melero I, Grande-Pulido E, Gurpide A, Gil-Bazo I, Calvo A. Identification of TNF-alpha and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array. Br J Cancer 2009. 101: 1876-1883. https://doi.org/10.1038/sj.bjc.6605409
  22. Punnonen J, Aversa G, Cocks BG, de Vries JE. Role of interleukin- 4 and interleukin-13 in synthesis of IgE and expression of CD23 by human B cells. Allergy 1994. 49: 576-586. https://doi.org/10.1111/j.1398-9995.1994.tb00122.x
  23. Sakata K, Hirose Y, Qiao Z, Tanaka T, Mori H. Inhibition of inducible isoforms of cyclooxygenase and nitric oxide synthase by flavonoid hesperidin in mouse macrophage cell line. Cancer Lett. 2003. 199: 139-145. https://doi.org/10.1016/S0304-3835(03)00386-0
  24. Sur S, Lam J, Bouchard P, Sigounas A, Holbert D, Metzger WJ. Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses. J Immunol. 1996. 157: 4173-4180.
  25. Tanaka H, Komai M, Nagao K, Ishizaki M, Kajiwara D, Takatsu K. Role of interleukin-5 and eosinophils in allergen-induced airway remodeling in mice. Am J Respir Cell Mol Biol. 2004. 31: 62-68. https://doi.org/10.1165/rcmb.2003-0305OC
  26. Tanaka T, Kohno H, Murakami M, Shimada R, Kagami S, Sumida T, Azuma Y, Ogawa H. Suppression of azoxymethaneinduced colon carcinogenesis in male F344 rats by mandarin juices rich in a-cryptoxanthin and hesperidin. Int J Cancer 2000. 8: 146-150.
  27. Tournoy KG, Kips JC, Schou C, Pauwels RA. Airway eosinophilia is not a requirement for allergen-induced airway hyperresponsiveness. Clin Exp Allergy 2000. 30: 7985.
  28. Vinson JA, Liang X, Proch J, Honzt BA, Dancel J, Sandone N. Polyphenol antioxidants in citrus juices: In Vitro and in Vivo studies relevant to heart disease. Adv Exp Med Biol. 2002. 505: 113-122.
  29. Yeh CC, Kao SJ, Lin CC, Wang SD, Liu CJ, Kao ST. The immunomodulation of endotoxin-induced acute lung injury by hesperidin in vivo and in vitro. Life Sci. 2007. 80: 1821 -1831. https://doi.org/10.1016/j.lfs.2007.01.052