Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지
DOI QR코드

DOI QR Code

The Inhibitory Effect of Premature Citrus unshiu Extract on Atopic Dermatitis In Vitro and In Vivo

  • Kang, Gyeoung-Jin (Department of Pharmacology, School of Medicine, Jeju National University) ;
  • Han, Sang-Chul (Department of Pharmacology, School of Medicine, Jeju National University) ;
  • Yi, Eun-Jou (Department of Clothing & Textiles, College of Natural Sciences, Jeju National University) ;
  • Kang, Hee-Kyoung (Department of Pharmacology, School of Medicine, Jeju National University) ;
  • Yoo, Eun-Sook (Department of Pharmacology, School of Medicine, Jeju National University)
  • Received : 2011.07.01
  • Accepted : 2011.08.14
  • Published : 2011.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease that is associated with Th2 cell-mediated allergy. The process that leads to infiltration of inflammatory cells into an AD lesion is remarkably dependent on various chemokines, especially TARC (thymus and activation-regulated chemokine/CCL17) and MDC (macrophage-derived chemokine/CCL22). Serum levels of these chemokines are over-expressed in AD patients. Citrus unshiu, which is known as Satsuma mandarin, has anti-oxidative, anti-inflammation, and anti-microviral activity. Therefore, we investigated the effect of EtOH extract of premature C. unshiu on AD. We did this using a DNCB-induced AD mouse model. We also tried to confirm an inhibitory effect for premature C. unshiu on the expression of inflammatory chemokines in IFN-${\gamma}$ and TNF-${\alpha}$ stimulated HaCaT human keratinocytes. We found that extract of premature C. unshiu reduced DNCB-induced symptoms such as hyperkeratosis, increased skin thickness, and infiltrated mast cells, in our AD-like animal model. The extract decreased levels of IFN-${\gamma}$ and IL-4 in ConA-stimulated splenocytes isolated from DNCB-treated mice. Also, extract of premature C. unshiu inhibited mRNA expression and protein production of TARC and MDC through the inhibition of STAT1 phosphorylation. These results suggest that C. unshiu has anti-atopic activity by regulating inflammatory chemokines such as TARC and MDC.

Keywords

References

  1. Abramovits, W. (2005). Atopic dermatitis. J. Am. Acad. Dermatol., 53, S86-93. https://doi.org/10.1016/j.jaad.2005.04.034
  2. Bonness, S. and Bieber, T. (2007). Molecular basis of atopic dermatitis. Curr. Opin. Allergy Clin. Immunol., 7, 382-386. https://doi.org/10.1097/ACI.0b013e3282a643c3
  3. Choi, I.Y., Kim, S.J., Jeong, H.J., Park, S.H., Song, Y.S., Lee, J.H., Kang, T.H., Park, J.H., Hwang, G.S., Lee, E.J., Hong, S.H., Kim, H.M. and Um, J.Y. (2007). Hesperidin inhibits expression of hypoxia inducible factor-1 alpha and inflammatory cytokine production from mast cells. Mol. Cell Biochem., 305, 153-161. https://doi.org/10.1007/s11010-007-9539-x
  4. Gough, D.J., Levy, D.E., Johnstone, R.W. and Clarke, C.J. (2008). IFNgamma signaling-does it mean JAK-STAT? Cytokine. Growth Factor Rev., 19, 383-394. https://doi.org/10.1016/j.cytogfr.2008.08.004
  5. Harasstani, O.A., Moin, S., Tham, C.L., Liew, C.Y., Ismail, N., Rajajendram, R., Harith, H.H., Zakaria, Z.A., Mohamad, A.S., Sulaiman, M.R. and Israf, D.A. (2010). Flavonoid combinations cause synergistic inhibition of proinflammatory mediator secretion from lipopolysaccharide-induced RAW 264.7 cells. Inflamm. Res., 59, 711-721. https://doi.org/10.1007/s00011-010-0182-8
  6. Hijnen, D., De Bruin-Weller, M., Oosting, B., Lebre, C., De Jong, E., Bruijnzeel-Koomen, C. and Knol, E. (2004). Serum thymus and activation-regulated chemokine (TARC) and cutaneous T cell- attracting chemokine (CTACK) levels in allergic diseases: TARC and CTACK are disease-specific markers for atopic dermatitis. J. Allergy Clin. Immunol., 113, 334-340. https://doi.org/10.1016/j.jaci.2003.12.007
  7. Imai, T., Nagira, M., Takagi, S., Kakizaki, M., Nishimura, M., Wang, J., Gray, P.W., Matsushima, K. and Yoshie, O. (1999). Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine. Int. Immunol., 11, 81-88. https://doi.org/10.1093/intimm/11.1.81
  8. Itoh, K., Masuda, M., Naruto, S., Murata, K. and Matsuda, H. (2009). Antiallergic activity of unripe Citrus hassaku fruits extract and its flavanone glycosides on chemical substanceinduced dermatitis in mice. J. Nat. Med., 63, 443-450. https://doi.org/10.1007/s11418-009-0349-1
  9. Jin, H., He, R., Oyoshi, M. and Geha, R.S. (2009). Animal models of atopic dermatitis. J. Invest. Dermatol., 129, 31-40. https://doi.org/10.1038/jid.2008.106
  10. Ju, S.M., Song, H.Y., Lee, S.J., Seo, W.Y., Sin, D.H., Goh, A.R., Kang, Y.H., Kang, I.J., Won, M.H., Yi, J.S., Kwon, D.J., Bae, Y.S., Choi, S.Y. and Park, J. (2009). Suppression of thymusand activation-regulated chemokine (TARC/CCL17) production by 1,2,3,4,6-penta-O-galloyl-beta-D-glucose via blockade of NF-kappaB and STAT1 activation in the HaCaT cells. Biochem. Biophys. Res. Commun., 387, 115-120. https://doi.org/10.1016/j.bbrc.2009.06.137
  11. Kakinuma, T., Nakamura, K., Wakugawa, M., Mitsui, H., Tada, Y., Saeki, H., Torii, H., Komine, M., Asahina, A. and Tamaki, K. (2002). Serum macrophage-derived chemokine (MDC) levels are closely related with the disease activity of atopic dermatitis. Clin. Exp. Immunol., 127, 270-273. https://doi.org/10.1046/j.1365-2249.2002.01727.x
  12. Kang, Y.J., Yang, M.H., Ko, W.J., Park, S.R. and Lee, B.G. (2005). Studies on the major components and antioxidative properties of whole fruit powder and juice prepared from premature mandarin orange. Korean J. Food Sci. Technol., 37, 783-788.
  13. Kim, Y.D., Mahinda, S., Koh, K.S., Jeon, Y.J. and Kim, S.H. (2009). Reactive Oxygen Species Scavenging Activity of Jeju Native Citrus Peel during Maturation. J. Korean Soc. Food Sci. Nutr., 38, 462-469. https://doi.org/10.3746/jkfn.2009.38.4.462
  14. Kitagaki, H., Fujisawa, S., Watanabe, K., Hayakawa, K. and Shiohara, T. (1995). Immediate-type hypersensitivity response followed by a late reaction is induced by repeated epicutaneous application of contact sensitizing agents in mice. J. Invest. Dermatol., 105, 749-755. https://doi.org/10.1111/1523-1747.ep12325538
  15. Lee, E.J., Ji, G.E. and Sung, M.K. (2010). Quercetin and kaempferol suppress immunoglobulin E-mediated allergic inflammation in RBL-2H3 and Caco-2 cells. Inflamm. Res., 59, 847-854. https://doi.org/10.1007/s00011-010-0196-2
  16. Lee, S.H., Heo, Y. and Kim, Y.C. (2010). Effect of German chamomile oil application on alleviating atopic dermatitis-like immune alterations in mice. J. Vet. Sci., 11, 35-41. https://doi.org/10.4142/jvs.2010.11.1.35
  17. Leung, T.F., Ma, K.C., Hon, K.L., Lam, C.W., Wan, H., Li, C.Y. and Chan, I.H. (2003). Serum concentration of macrophagederived chemokine may be a useful inflammatory marker for assessing severity of atopic dermatitis in infants and young children. Pediatr. Allergy Immunol., 14, 296-301. https://doi.org/10.1034/j.1399-3038.2003.00052.x
  18. Matsumoto, K., Mizukoshi, K., Oyobikawa, M., Ohshima, H., Sakai, Y. and Tagami, H. (2005). Objective evaluation of the efficacy of daily topical applications of cosmetics bases using the hairless mouse model of atopic dermatitis. Skin Res. Technol., 11, 209-217. https://doi.org/10.1111/j.1600-0846.2005.00106.x
  19. Matsumoto, K., Mizukoshi, K., Oyobikawa, M., Ohshima, H. and Tagami, H. (2004). Establishment of an atopic dermatitis-like skin model in a hairless mouse by repeated elicitation of contact hypersensitivity that enables to conduct functional analyses of the stratum corneum with various non-invasive biophysical instruments. Skin Res. Technol., 10, 122-129. https://doi.org/10.1111/j.1600-0846.2004.00062.x
  20. Murakami, A., Nakamura, Y., Torikai, K., Tanaka, T., Koshiba, T., Koshimizu, K., Kuwahara, S., Takahashi, Y., Ogawa, K., Yano, M., Tokuda, H., Nishino, H., Mimaki, Y., Sashida, Y., Kitanaka, S. and Ohigashi, H. (2000). Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice. Cancer Res., 60, 5059-5066.
  21. Nakazato, J., Kishida, M., Kuroiwa, R., Fujiwara, J., Shimoda, M. and Shinomiya, N. (2008). Serum levels of Th2 chemokines, CCL17, CCL22, and CCL27, were the important markers of severity in infantile atopic dermatitis. Pediatr. Allergy Immunol., 19, 605-613.
  22. Pease, J.E. and Williams, T.J. (2006). Chemokines and their receptors in allergic disease. J. Allergy Clin. Immunol., 118, 305-318. https://doi.org/10.1016/j.jaci.2006.06.010
  23. Qi, X.F., Kim, D.H., Yoon, Y.S., Li, J.H., Jin, D., Deung, Y.K. and Lee, K.J. (2009). Effects of Bambusae caulis in Liquamen on the development of atopic dermatitis-like skin lesions in hairless mice. J. Ethnopharmacol., 123, 195-200. https://doi.org/10.1016/j.jep.2009.03.020
  24. Qi, X.F., Teng, Y.C., Yoon, Y.S., Kim, D.H., Cai, D.Q. and Lee, K.J. (2011). Reactive oxygen species are involved in the IFN-gamma-stimulated production of Th2 chemokines in HaCaT keratinocytes. J. Cell Physiol., 226, 58-65. https://doi.org/10.1002/jcp.22303
  25. Saha, B., Jyothi Prasanna, S., Chandrasekar, B. and Nandi, D. (2010). Gene modulation and immunoregulatory roles of interferon gamma. Cytokine., 50, 1-14. https://doi.org/10.1016/j.cyto.2009.11.021
  26. Sakata, K., Hirose, Y., Qiao, Z., Tanaka, T. and Mori, H. (2003). Inhibition of inducible isoforms of cyclooxygenase and nitric oxide synthase by flavonoid hesperidin in mouse macrophage cell line. Cancer Lett., 199, 139-145. https://doi.org/10.1016/S0304-3835(03)00386-0
  27. Vestergaard, C., Yoneyama, H., Murai, M., Nakamura, K., Tamaki, K., Terashima, Y., Imai, T., Yoshie, O., Irimura, T., Mizutani, H. and Matsushima, K. (1999). Overproduction of Th2-specific chemokines in NC/Nga mice exhibiting atopic dermatitis-like lesions. J. Clin. Invest., 104, 1097-1105. https://doi.org/10.1172/JCI7613
  28. Yoshimura, A., Naka, T. and Kubo, M. (2007). SOCS proteins, cytokine signalling and immune regulation. Nat. Rev. Immunol., 7, 454-465. https://doi.org/10.1038/nri2093

Cited by

  1. The Chloroform Fraction of Carpinus tschonoskii Leaves Inhibits the Production of Inflammatory Mediators in HaCaT Keratinocytes and RAW264.7 Macrophages vol.28, pp.4, 2012, https://doi.org/10.5487/TR.2012.28.4.255
  2. Anti-Inflammatory Effect of Quercetagetin, an Active Component of Immature Citrus unshiu, in HaCaT Human Keratinocytes vol.21, pp.2, 2013, https://doi.org/10.4062/biomolther.2013.001
  3. Quercetagetin inhibits macrophage-derived chemokine in HaCaT human keratinocytes via the regulation of signal transducer and activator of transcription 1, suppressor of cytokine signalling 1 and transforming growth factor-β1 vol.171, pp.3, 2014, https://doi.org/10.1111/bjd.12938
  4. Effect of natural flavonoids, stilbenes and caffeic acid oligomers on protein glycation vol.2, pp.5, 2014, https://doi.org/10.3892/br.2014.304
  5. Ethanolic Extracts of Artemisia apiacea Hance Improved Atopic Dermatitis-Like Skin Lesions In Vivo and Suppressed TNF-Alpha/IFN-Gamma–Induced Proinflammatory Chemokine Production In Vitro vol.10, pp.7, 2018, https://doi.org/10.3390/nu10070806