The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology (한방안이비인후피부과학회지)

The Society of Korean Medicine Ophthalmology, Otolaryngology & Dermatology (대한한방안이비인후피부과학회)
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The Effects of Orally Administrated Gwakhyangjeonggi-san on DNCB-induced Atopic Dermatitis like Mice Model

DNCB로 유발된 아토피 피부염 동물 모델에 대한 곽향정기산(藿香正氣散) 경구투여의 효과

  • Son, Mi-Ju (Clinical Medicine Division, Korea Institute of Oriental Medicine) ;
  • Lee, So-Min (Clinical Medicine Division, Korea Institute of Oriental Medicine) ;
  • Park, Seong-Hwan (Clinical Medicine Division, Korea Institute of Oriental Medicine) ;
  • Kim, Young-Eun (Future Medicine Division, Korea Institute of Oriental Medicine) ;
  • Jung, Jee-Youn (Clinical Medicine Division, Korea Institute of Oriental Medicine)
  • 손미주 (한국한의학연구원 임상의학부) ;
  • 이소민 (한국한의학연구원 임상의학부) ;
  • 박성환 (한국한의학연구원 임상의학부) ;
  • 김영은 (한국한의학연구원 미래의학부) ;
  • 정지연 (한국한의학연구원 임상의학부)
  • Received : 2019.04.19
  • Accepted : 2019.05.02
  • Published : 2019.05.25
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Abstract

Objectives : This study was conducted to investigate the effects of Gwakhyangjeonggi-san(GJS) on atopic dermatitis(AD) induced by 2,4-dinitrochlorobenzene(DNCB) in mice. Methods : The mice(Balb/c mice) were divided into three groups; normal Balb/c mice with oil treatment(Sham group), DNCB-induced AD mice(AD group), and GJS treated AD mice(GJS group). GJS group were orally administered GJS daily for 2 weeks. We observed changes of clinical skin severity score, the expression of thymic stromal lymphopoietin(TSLP), interleukin(IL)-4 and tumor necrosis factor(TNF)-${\alpha}$ in skin and mast cell infiltration. Also, serum immunoglobulinE(IgE), IL-4, $TNF-{\alpha}$ and IL-6 were evaluated. Results : The clinical skin severity score of GJS group was decreased compared to AD group. In hematoxylin and eosin staining results, GJS group showed a significant reduction of epithelial skin thickness. In addition, expression of TSLP and mast cell infiltration in skin were also reduced by GJS treatment compared to those of AD group. Thus, we evaluated expression of IL-4, Th2-dependent cytokine, and $TNF-{\alpha}$, pro-inflammatory cytokine in skin. GJS significantly reduced both IL-4 and $TNF-{\alpha}$ compared to AD mice. Moreover, levels of IgE, IL-4, $TNF-{\alpha}$ and IL-6 in plasma also significantly decreased by oral GJS treatment. Conclusion : The present study suggests that GJS can significantly reduced symptoms of AD, therefore it can be a promising candidate for anti-atopic dermatitis treatment.

Keywords

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Fig. 1. Schematic Representation of the Experiment

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Fig. 2. Effects of Gwakhyangjeonggi-san(GJS) on Clinical Aspect in AD Induced Mice Sham, Normal mice with oil treatment; AD, DNCB-induced atopic dermatitis model; GJS, Orally GJS treated DNCB-induced atopic dermatitis model.

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Fig. 3. Change of Atopic Dermatitis Index after Gwakhyangjeonggi-san(GJS) Treatment

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Fig. 4. Histologic Features of Skin Lesion and Epithelial Thickness

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Fig. 5. Change of IgE Levels after Gwakhyangjeonggi-san(GJS) Treatment

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Fig. 6. Change of TSLP expression after Gwakhyangjeonggi-san(GJS) treatment

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Fig. 7. Change of Mast Cell Infiltration after Gwakhyangjeonggi-san(GJS) Treatment.

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Fig. 8. Change of Expression of IL-4 and TNF-α after Gwakhyangjeonggi-san(GJS) Treatment

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Fig. 9. Change of Expression of (A) IL-4, (B) TNF-α and (C) IL-6 after Gwakhyangjeonggi-san(GJS) Treatment

Table 1. Prescription of Gwakhyangjeonggi-san

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References

  1. Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. Journal of the American Academy of Dermatology. 2014;70(2):338-51. https://doi.org/10.1016/j.jaad.2013.10.010
  2. Ministry of Health and Welfare. Korea youth risk behavior survey [Internet]. Korean Statistical information service. 2018. Available from: URL: http://kosis.kr/statHtml/statHtml.do?orgId=117&tblId=DT_117_12_Y094&conn_path=I2.
  3. Ministry of Health and Welfare. Korea National Health and Nutrition Examination Survey [Internet]. 2019. Available from: URL: http://kosis.kr/statHtml/statHtml.do?orgId=117&tblId=DT_11702_N114&conn_path=I2.
  4. Krakowski AC, Eichenfield LF, Dohil MA. Management of atopic dermatitis in the pediatric population. Pediatrics. 2008;122(4):812-24. https://doi.org/10.1542/peds.2007-2232
  5. Jones MP, Walker MM, Ford AC, Talley NJ. The overlap of atopy and functional gastrointestinal disorders among 23,471 patients in primary care. Alimentary Pharmacology and Therapeutics. 2014;40(4):382-91. https://doi.org/10.1111/apt.12846
  6. Walker MM, Powell N, Talley NJ. Atopy and the gastrointestinal tract - a review of a common association in unexplained gastrointestinal disease. Expert Review of Gastroenterology and Hepatology. 2014;8(3):289-99. https://doi.org/10.1586/17474124.2014.881716
  7. Korea Institute of Oriental Medicine. Atopic dermatitis Korean Medicine Clinical Practice Guideline. Seoul: Elsevier Korea. 2015:30.
  8. Yuan Z, Cao Z, Guo Q, Yang Z. The Clinical Efficacy Observation of Huoxiang Zhengqi Caplsule to Functional Dyspepsia. Liaoning zhong yi zazhi. 2011; 38(3):494-6.
  9. Ko SJ, Han G, Kim SK, Seo JG, Chung WS, Ryu B, et al. Effect of Korean Herbal Medicine Combined with a Probiotic Mixture on Diarrhea-Dominant Irritable Bowel Syndrome: A Double-Blind, Randomized, Placebo-Controlled Trial. Evidence-based Complementary and Alternative Medicine. 2013;2013:1-10.
  10. Lee SY, Bae HS, Park SS. A Case Report of Soeumin Atopic Dermatitis Patient Improved by Gwakhyangjeonggi-san. Journal of Sasang Constitutional Medicine. 2010;22(4):106-12.
  11. Yang SW, Kim YB, Kim SY, Choi H, Sohn YJ, Park SK, et al. Effect of several herbal medicines on atopic dermatitis patients' SCORAD and cytokin levels. The Korean Journal of Oriental Medical Prescription. 2008;16(1):185-205.
  12. Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. Journal of Basic and Clinical Pharmacy. 2016;7(2):27-31. https://doi.org/10.4103/0976-0105.177703
  13. Rha YH, Choi SH. Risk factors associated with development of atopic dermatitis. Allergy Asthma & Respiratory Diseases. 2009;19(2):91-4.
  14. Palmer CN, Irvine AD, Terron- Kwiatkowski A, Zhao Y, Liao H, Lee SP, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nature Genetics. 2006;38(4):441-6. https://doi.org/10.1038/ng1767
  15. Strachan DP. Hay fever, hygiene, and household size. British Medical Journal. 1989;299(6710):1259-60. https://doi.org/10.1136/bmj.299.6710.1259
  16. Nutten S. Atopic Dermatitis: Global Epidemiology and Risk Factors. Annals of Nutrition and Metabolism. 2015;66(suppl 1):8-16. https://doi.org/10.1159/000370220
  17. Gu S, Yang AW, Xue CC, Li CG, Pang C, Zhang W, et al. Chinese herbal medicine for atopic eczema. Cochrane Database of Systematic Reviews. 2013;(9):1-132.
  18. Kobayashi H, Ishii M, Takeuchi S, Tanaka Y, Shintani T, Yamatodani A, et al. Efficacy and Safety of a Traditional Herbal Medicine, Hochu-ekki-to in the Long-term Management of Kikyo(Delicate Constitution) Patients with Atopic Dermatitis: A 6-month, Multicenter, Double-blind, Randomized, Placebo-controlled Study. Evidence-based Complementary and Alternative Medicine. 2010;7(3):367-73. https://doi.org/10.1093/ecam/nen003
  19. Cheng HM, Chiang LC, Jan YM, Chen GW, Li TC. The efficacy and safety of a Chinese herbal product(Xiao-Feng-San) for the treatment of refractory atopic dermatitis: a randomized, double-blind, placebo-controlled trial. International Archives of Allergy and Immunology. 2011;155(2):141-8. https://doi.org/10.1159/000318861
  20. Korea Institute of Oriental Medicine. Mediclassics [Internet]. Korea Institute of Oriental Medicine. 2015. [cited 19 Apr 2019]. Available from: URL: https://mediclassics.kr/books/8/volume/10#content_1156
  21. Jeong SJ, Kim OS, Yoo SR, Seo CS, Kim Y, Shin HK. Anti-inflammatory and antioxidant activity of the traditional herbal formula Gwakhyangjeonggisan via enhancement of heme oxygenase1 expression in RAW264.7 macrophages. Molecular Medicine Reports. 2016;13(5):4365-71. https://doi.org/10.3892/mmr.2016.5084
  22. Han Y. Experimental study on Huoxiangzhengqi decoction and it's drug-serum against allergic reaction. Kunming: Kunming medical university; 2006.
  23. Martel BC, Lovato P, Baumer W, Olivry T. Translational Animal Models of Atopic Dermatitis for Preclinical Studies. Yale Journal of Biology and Medicine. 2017;90(3):389-402.
  24. Yamaguchi T, Maekawa T, Nishikawa Y, Nojima H, Kaneko M, Kawakita T, et al. Characterization of itch-associated responses of NC mice with mite-induced chronic dermatitis. Journal of Dermatological Science. 2001;25(1):20-8. https://doi.org/10.1016/S0923-1811(00)00099-2
  25. Indra AK. Epidermal TSLP: a trigger factor for pathogenesis of atopic dermatitis. Expert Review of Proteomics. 2013;10(4):309-11. https://doi.org/10.1586/14789450.2013.814881
  26. Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nature Immunology. 2002;3(7):673-80. https://doi.org/10.1038/ni805
  27. Cianferoni A, Spergel J. The importance of TSLP in allergic disease and its role as a potential therapeutic target. Expert Review of Clinical Immunology. 2014;10(11):1463-74. https://doi.org/10.1586/1744666X.2014.967684
  28. Serezani APM, Bozdogan G, Sehra S, Walsh D, Krishnamurthy P, Sierra Potchanant EA, et al. IL-4 impairs wound healing potential in the skin by repressing fibronectin expression. The Journal of Allergy and Clinical Immunology. 2017;139(1):142-51.e5. https://doi.org/10.1016/j.jaci.2016.07.012
  29. Leung DYM. Role of IgE in atopic dermatitis. Current Opinion in Immunology. 1993;5(6):956-62. https://doi.org/10.1016/0952-7915(93)90112-6
  30. Danso MO, van Drongelen V, Mulder A, van Esch J, Scott H, van Smeden J, et al. $TNF-{\alpha}$ and Th2 Cytokines Induce Atopic Dermatitis-Like Features on Epidermal Differentiation Proteins and Stratum Corneum Lipids in Human Skin Equivalents. Current Opinion in Immunology. 2014;134(7):1941-50.
  31. Sumimoto S, Kawai M, Kasajima Y, Hamamoto T. Increased plasma tumour necrosis factor-alpha concentration in atopic dermatitis. Archives of Disease in Childhood. 1992;67(3):277-9. https://doi.org/10.1136/adc.67.3.277
  32. Toshitani A, Ansel JC, Chan SC, Li SH, Hanifin JM. Increased Interleukin 6 Production by T Cells Derived from Patients with Atopic Dermatitis. Journal of Investigative Dermatology. 1993;100(3):299-304. https://doi.org/10.1111/1523-1747.ep12469875