Korean Journal of Pharmacognosy (생약학회지)

The Korean Society of Pharmacognosy (한국생약학회)
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Suppressive Effects of Hesperidin on Th2-associated Cytokines Expression in RBL-2H3 Cells

RBL-2H3 세포에서 Hesperidin의 Th2 사이토카인 발현 억제 효과

  • 정화현 (숙명여자대학교 약학대학) ;
  • 김순례 (숙명여자대학교 약학대학) ;
  • 표명윤 (숙명여자대학교 약학대학)
  • Received : 2013.04.23
  • Accepted : 2013.06.03
  • Published : 2013.06.30
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Abstract

Hesperidin (HES), a flavonone glycoside isolated from the citrus fruits such as lemons and oranges, has been reported to have many biological properties including antiinflammatory, antioxidant, and antiallergy activities. In this study, we focused on the action of HES modulating Th2-associated cytokines such as IL-4 and IL-13 expression in PMA/ionomycin (PI)-stimulated rat basophilic leukemia (RBL-2H3) cells. The production of IL-4 and IL-13 was quantified by ELISA and the mRNA expression was detected by using RT-PCR assay. In addition, western blot analysis was performed to determine the transcription factors involved in the cytokine expression. We found that HES significantly decreased PI-induced IL-4 and IL-13 productions and also decreased the level of mRNA in a dose-dependent manner. Furthermore, western blot analysis of the transcription factors implied that HES down-regulated the protein level of c-Jun and c-Fos, which are the activating protein 1 (AP-1) family and nuclear factor-kappaB (NF-${\kappa}B$) characterized as a transcription factors related to the Th2-associated cytokine expression. Taken together, our data showed that the action of HES responsible for antiallergy activities is based on suppression of Th2-associated cytokines through inhibition of AP-1 and NF-${\kappa}B$ transcription factors.

Keywords

References

  1. 한국약학교육협의회 예방약학분과회 (2013) 질환별로 본 건강기능식품학, 251. (주)신일북스, 서울.
  2. Abbas, A. K., L. A. H., and Baker, D. L. (2008) Basic Immunology, 205-211. W. B. Saunders Company, Philadelphia.
  3. Prussin, C. and Metcalfe, D. D. (2003) 4. IgE, mast cells, basophils, and eosinophils. J. Allergy Clin. Immunol. 111: S486-S494. https://doi.org/10.1067/mai.2003.120
  4. Falcone, F. H., Zillikens, D., and Gibbs, B. F. (2006) The 21st century renaissance of the basophil? Current insights into its role in allergic responses and innate immunity. Exp. Dermatol. 15: 855-864. https://doi.org/10.1111/j.1600-0625.2006.00477.x
  5. Schmid-Grendelmeier, P., Altznauer, F., Fischer, B., Bizer, C., Straumann, A., Menz, G., Blaser, K., Wuthrich, B., and Simon, H. U. (2002) Eosinophils express functional IL-13 in eosinophilic inflammatory diseases. J. Immunol. 169: 1021- 1027. https://doi.org/10.4049/jimmunol.169.2.1021
  6. Junttila, I. S., Mizukami, K., Dickensheets, H., Meier- Schellersheim, M., Yamane, H., Donnelly, R. P., and Paul, W. E. (2008) Tuning sensitivity to IL-4 and IL-13: differential expression of IL-4Ralpha, IL-13Ralpha1, and gammac regulates relative cytokine sensitivity. J. Exp. Med. 205: 2595- 2608. https://doi.org/10.1084/jem.20080452
  7. Liang, H. E., Reinhardt, R. L., Bando, J. K., Sullivan, B. M., Ho, I. C., and Locksley, R. M. (2012) Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunity. Nat. Immunol. 13: 58-66.
  8. Wynn, T. A. (2003) IL-13 effector functions. Annu. Rev. Immunol. 21: 425-456. https://doi.org/10.1146/annurev.immunol.21.120601.141142
  9. Brusselle, G. G., Kips, J. C., Tavernier, J. H., van der Heyden, J. G., Cuvelier, C. A., Pauwels, R. A., and Bluethmann, H. (1994) Attenuation of allergic airway inflammation in IL-4 deficient mice. Clin. Exp. Allergy 24: 73-80. https://doi.org/10.1111/j.1365-2222.1994.tb00920.x
  10. Zavorotinskaya, T., Tomkinson, A. and Murphy, J. E. (2003) Treatment of experimental asthma by long-term gene therapy directed against IL-4 and IL-13. Mol. Ther. 7: 155-162. https://doi.org/10.1016/S1525-0016(02)00050-3
  11. Elias, J. A., Zheng, T., Lee, C. G., Homer, R. J., Chen, Q., Ma, B., Blackburn, M. and Zhu, Z. (2003) Transgenic modeling of interleukin-13 in the lung. Chest 123: 339S-345S.
  12. Yu, M. W., Lou, S. N., Chiu, E. M., and Ho, C. T. (2013) Antioxidant activity and effective compounds of immature calamondin peel. Food Chem. 136: 1130-1135. https://doi.org/10.1016/j.foodchem.2012.09.088
  13. Jain, M. and Parmar, H. S. (2011) Evaluation of antioxidative and anti-inflammatory potential of hesperidin and naringin on the rat air pouch model of inflammation. Inflamm. Res. 60: 483-491. https://doi.org/10.1007/s00011-010-0295-0
  14. Hosseinimehr, S. J., Jalayer, Z., Naghshvar, F., and Mahmoudzadeh, A. (2012) Hesperidin inhibits cyclophosphamide- induced tumor growth delay in mice. Integr Cancer Ther. 11: 251-256. https://doi.org/10.1177/1534735412448959
  15. Meiyanto, E., Hermawan, A., and Anindyajati (2012) Natural products for cancer-targeted therapy: citrus flavonoids as potent chemopreventive agents. Asian Pac. J. Cancer Prev. 13: 427-436. https://doi.org/10.7314/APJCP.2012.13.2.427
  16. Li, R., Li, J., Cai, L., Hu, C. M., and Zhang, L. (2008) Suppression of adjuvant arthritis by hesperidin in rats and its mechanisms. J. Pharm. Pharmacol. 60: 221-228. https://doi.org/10.1211/jpp.60.2.0011
  17. Shi, X., Liao, S., Mi, H., Guo, C., Qi, D., Li, F., Zhang, C., and Yang, Z. (2012) Hesperidin prevents retinal and plasma abnormalities in streptozotocin-induced diabetic rats. Molecules 17: 12868-12881. https://doi.org/10.3390/molecules171112868
  18. Sahu, B. D., Kuncha, M., Sindhura, G. J., and Sistla, R. (2013) Hesperidin attenuates cisplatin-induced acute renal injury by decreasing oxidative stress, inflammation and DNA damage. Phytomedicine 20: 453-460. https://doi.org/10.1016/j.phymed.2012.12.001
  19. Wei, D., Ci, X., Chu, X., Wei, M., Hua, S., and Deng, X. (2012) Hesperidin suppresses ovalbumin-induced airway inflammation in a mouse allergic asthma model. Inflammation 35: 114-121. https://doi.org/10.1007/s10753-011-9295-7
  20. Chang, J. H. (2010) Anti-inflammatory effects and its mechanisms of hesperidin in an asthmatic mouse model induced by ovalbumin J. Exp. Biomed. Sci. 16: 83-90.
  21. Han, N. R., Kim, H. M., and Jeong, H. J. (2012) Pyeongwee- San extract (KMP6): a new anti-allergic effect. J. Pharm. Pharmacol. 64: 308-316. https://doi.org/10.1111/j.2042-7158.2011.01405.x
  22. Park, S. H., Park, E. K., and Kim, D. H. (2005) Passive cutaneous anaphylaxis-inhibitory activity of flavanones from Citrus unshiu and Poncirus trifoliata. Planta Med. 71: 24-27. https://doi.org/10.1055/s-2005-837746
  23. Klein, P. A. and Clark, R. A. (1999) An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis. Arch. Dermatol. 135: 1522-1525.
  24. Sidbury, R. and Hanifin, J. M. (2000) Systemic therapy of atopic dermatitis. Clin. Exp. Dermatol. 25: 559-566. https://doi.org/10.1046/j.1365-2230.2000.00697.x
  25. Behnam, S. M., Behnam, S. E., and Koo, J. Y. (2005) Review of cyclosporine immunosuppressive safety data in dermatology patients after two decades of use. J. Drugs Dermatol. 4: 189-194.
  26. Apgar, J. R. (1991) Association of the crosslinked IgE receptor with the membrane skeleton is independent of the known signaling mechanisms in rat basophilic leukemia cells. Cell Regul. 2: 181-191.
  27. Kim, S. H., Kim, B. K., and Lee, Y. C. (2011) Antiasthmatic effects of hesperidin, a potential Th2 cytokine antagonist, in a mouse model of allergic asthma. Mediators Inflamm. 2011: 1-12.
  28. Yeh, C. C., Kao, S. J., Lin, C. C., Wang, S. D., Liu, C. J., and Kao, S. T. (2007) The immunomodulation of endotoxininduced acute lung injury by hesperidin in vivo and in vitro. Life Sci. 80: 1821-1831. https://doi.org/10.1016/j.lfs.2007.01.052
  29. Lee, N. K., Choi, S. H., Park, S. H., Park, E. K., and Kim, D. H. (2004) Antiallergic activity of hesperidin is activated by intestinal microflora. Pharmacology 71: 174-180. https://doi.org/10.1159/000078083
  30. Hayden, M. S., and Ghosh, S. (2004) Signaling to NF-kappaB. Genes Dev. 18: 2195-2224. https://doi.org/10.1101/gad.1228704
  31. Boguniewicz, M., Schmid-Grendelmeier, P., & Leung, D. Y. (2006) Atopic dermatitis. J Allergy Clin Immunol. 118: 40-43. https://doi.org/10.1016/j.jaci.2006.04.044
  32. Kobayashi, S. and Tanabe, S. (2006) Evaluation of the antiallergic activity of Citrus unshiu using rat basophilic leukemia RBL-2H3 cells as well as basophils of patients with seasonal allergic rhinitis to pollen. Int. J. Mol. Med. 17: 511-515