DOI QR코드

DOI QR Code

The Combined Effects of Curcumin Administration and 630 nm LED Phototherapy against DNCB-induced Atopic Dermatitis-like Skin Lesions in BALB/c Mice

BALB/c 마우스에서 DNCB-유도 아토피 피부염 유사병변에 대한 Curcumin 투여와 630 nm LED 광치료의 병용 효과

  • Jekal, Seung-Joo (Department of Clinical Laboratory Science, Wokkwang Health Science University) ;
  • Park, Mi-Suk (Department of Clinical Pathology, Gwangyang Health Science University) ;
  • Kim, Dae-Jung (Department of Laboratory Medicine, Budang Jesaeng Hospital)
  • 제갈승주 (원광보건대학교 임상병리과) ;
  • 박미숙 (광양보건대학교 임상병리과) ;
  • 김대중 (분당제생병원 진단검사의학과)
  • Received : 2017.04.18
  • Accepted : 2017.04.24
  • Published : 2017.06.30

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease. It is characterized by eczematous lesions, skin dryness, and pruritus. The existing treatment drugs for AD have side effects, especially if the drugs are taken for extended periods. Therefore, new alternative therapies are necessary. The aim of this study was to investigate the combined effects of curcumin administration and LED irradiation on AD. AD-like lesions were induced in BALB/c mice by repeated application of 1-chloro-2,4-dinitrobenzene (DNCB) to the shaved skin of the ear and neck. Thirty male BALB/c mice were divided into five groups: vehicle, DNCB, curcumin, LED, and curcumin+LED groups. Curcumin (0.1 g/kg/day) was administrated repeatedly during a period of 14 days (experimental period) and 630 nm LED irradiation ($5J/cm^2/day$) was performed in the acryl box once a day for 10 days, after inducing AD-like lesions via DNCB application. The severity of AD-like lesions was evaluated during the experimental period, using a modified SCORAD index. Both ear and neck skin tissues were examined histologically for epidermal thickness, mast cell, eosinophil counting, and dermal collagen density. Epidermal cell proliferation and apoptosis were detected using immunohistochemistry and TUNEL, respectively. These were all reduced in SCORAD index, epidermal thickness, collagen density, number of mast cell and eosinophil in dermis, and number of proliferating cell and apoptotic cell in epidermis by curcumin administration and 630 nm LED irradiation. Moreover, all parameters were significantly lower in the curcumin+LED group compared with the curcumin group and LED group. These results suggest that the combined therapy of curcumin and LED is more effective than a single treatment. We recommend that this can be a feasible alternative therapy to manage AD.

아토피피부염은 만성 염증성 피부질환으로 습진성병변, 피부건조 및 가려움증의 특징적 증상을 보이는 질환이다. 현재 사용되고 있는 아토피피부염 치료약제들은 오래 사용시 여러 부작용이 있어서 이를 대신할 새로운 대체 치료법의 개발이 요구되고 있다. Curcumin은 항염, 항알러지와 같은 효과를 나타내는 천연 폴리페놀(polyphenol)이며, 발광다이오드(light emitting diode, LED) 광치료는 아토피피부염과 상처치유에 효과가 있는 것으로 알려져 있다. 본 연구는 DNCB로 유도한BALB/c 마우스의 아토피피부염에서 curcumin 투여와 630 nm LED 조사를 병용하여 그 치료 효과를 높일 수 있는가를 조사하기 위해 시도하였다. 아토피피부염의 치료 효과를 조사하기 위해 modified SCORAD 지수, 조직병리학적 분석, 면역조직화학염색 및 TUNEL 검사를 사용하였다. 그 결과 curcumin 투여와 630 nm LED 조사가 각각 SCORAD 지수, 비만세포 및 탈과립세포의 수, 호산구 수, 표피세포의 증식능 및 자멸세포의 수를 의미 있게 감소시키고, 비만세포의 탈과립을 억제하여 섬유모세포에 의한 콜라겐 생성을 의미 있게 감소시켰으며, curcumin 투여와 LED 조사를 병용하였을 경우 단일 처리군에 비해 이들 수치가 의미 있게 감소하는 것을 확인하였다. 이러한 결과는 아토피피부염 치료에 curcumin 투여와 LED 조사가 각각 효과가 있음을 의미하며, 병용 치료 시 그 효과가 좀 더 향상된다는 것을 의미하는 것으로, 아토피피부염의 대체치료 전략으로 curcumin 투여와 630 nm 조사의 병용 치료를 제안한다.

Keywords

References

  1. Hartmann B, Riedel R, Jorss K, Loddenkemper C, Steinmeyer A, Zugel U, Babina M, et al. Vitamin D receptor activation improves allergen-triggered eczema in mice. J Invest Dermatol. 2012;132(2):330-336. https://doi.org/10.1038/jid.2011.296
  2. Boguniewicz M, Leung DY. Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev. 2011;242(1):233-246. https://doi.org/10.1111/j.1600-065X.2011.01027.x
  3. Bieber T. Atopic dermatitis. Ann Dermatol. 2010;22(2):125-137. https://doi.org/10.5021/ad.2010.22.2.125
  4. Dubois GR, Bruijnzeel PL. IL-4-induced migration of eosinophils in allergic inflammation. Ann N Y Acad Sci. 1994;725:268-273. https://doi.org/10.1111/j.1749-6632.1994.tb39809.x
  5. Incorvaia C, Frati F, Verna N, D'Alo S, Motolese A, Pucci S. Allergy and the skin. Clin Exp Immunol. 2008;153(1):27-29. https://doi.org/10.1111/j.1365-2249.2008.03718.x
  6. Joo YH, Won CH, Kim JY, Cho KH, Min KU, Kim KH. Developing an atopic dermatitis model and the effects of actinidia extract on dermatitis in NC/Nga mice. Korean J Dermatol. 2009;47(10):1105-1112.
  7. Smuith CH. New approaches to topical therapy. Clin Exp Dermatol. 2000;25(7):567-574. https://doi.org/10.1046/j.1365-2230.2000.00706.x
  8. Lee JH, Kim JW, Ko NY, Mun SH, Her E, Kim BK, et al. Curcumin, a constituent of curry, suppresses IgE-mediated allergic response and mast cell activation at the level of Syk. J Allergy Clin Immunol. 2008;121(5):1225-1231. https://doi.org/10.1016/j.jaci.2007.12.1160
  9. Kim CH, Cheong KA, Lee AY. 850nm light-emitting-diode phototherapy plus low-dose tacrolimus (FK-506) as combination therapy in the treatment of Dermatophagoides farinae-induced atopic dermatitis-like skin lesions in NC/Nga mice. J Dermatol Sci. 2013;72(2):142-148. https://doi.org/10.1016/j.jdermsci.2013.06.002
  10. Brouet I, Ohshima H. Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem Biophys Res Commun. 1995;206(2):533-540. https://doi.org/10.1006/bbrc.1995.1076
  11. Ram A, Das M, Ghosh B. Curcumin attenuates allergen-induced airway hyperresponsiveness in sensitized guinea pigs. Biol Pharm Bull. 2003;26(7):1021-1024. https://doi.org/10.1248/bpb.26.1021
  12. Dall Agnol MA, Nicolau RA, de Lima CJ, Munin E. Comparative analysis of coherent light action (laser) versus non-coherent light (light-emitting diode) for tissue repair in diabetic rats. Lasers Med Sci. 2009;24(8):909-916. https://doi.org/10.1007/s10103-009-0648-5
  13. Barolet D. Light-emitting diodes (LEDs) in dermatology. Semin Cutan Med Surg. 2008;27(4):227-238. https://doi.org/10.1016/j.sder.2008.08.003
  14. Lim YY, Jang WS, Kim HM, Kim IS, Lee JW, Kim MN, et al. Therapeutic effects of light emitting diode on atopic dermatitis-like lesions in NC/Nga mice. Korean J Asthma Allergy Clin Immunol 2011;3(3):207-214.
  15. Kalka K, Merk H, Mukhtar H. Photodynamic therapy in dermatology. J Am Acad Dermatol. 2000;42(3):389-413. https://doi.org/10.1016/S0190-9622(00)90209-3
  16. Simpson CR, Kohl M, Essenpreis M, Cope M. Near-infrared optical properties of ex vivo human skin and subcutaneous tissues measured using the Monte Carlo inversion technique. Phys Med Biol. 1998;43(9):2465-2478. https://doi.org/10.1088/0031-9155/43/9/003
  17. Jekal SJ, Kwon PS, Kim JK. Effect of 630 nm light emitting diode (LED) irradiation on wound healing in streptozotocin-induced diabetic rats. J Exp Biomed Sci. 2010;16(4):1-12.
  18. Jekal SJ, Kwon PS, Kim JK, Lee JH. Effect of 840 nm light-emitting diode (LED) irradiation on monosodium iodoacetate-induced osteoarthritis in rats. J Korean Soc Phys Med. 2014;9(2):151-159. https://doi.org/10.13066/kspm.2014.9.2.151
  19. Kim CH, Cheong KA, Lim WS, Park HM, Lee AY. Effect of low-dose light-emitting-diode therapy in combination with water bath for atopic dermatitis in NC/Nga mice. Photodermatol Photoimmunol Photomed. 2016;32(1):34-43. https://doi.org/10.1111/phpp.12220
  20. Kim JY, Jeong MS, Choi SE, Kim JY, Park KY, Park KH, et al. The effects of acer ginnala leaves extraction on the atopic dermatitis-like skin lesions in NC/Nga mice. Korean J Dermatol. 2010;48(11):913-918.
  21. Enerback L. Mast cells in rat gastrointestinal tract: Effect of fixation. Acta Pathol Microbiol Scand. 1966;66:289-302. https://doi.org/10.1111/apm.1966.66.3.289
  22. Holgate ST. The epithelium takes centre stage in asthma and atopic dermatitis. Trends Immunol. 2007;28(6):248-251. https://doi.org/10.1016/j.it.2007.04.007
  23. Esche C, De Benedetto A, Beck LA. Keratinocytes in atopic dermatitis: inflammatory signals. Curr Allergy and Asthma Rep. 2004;4(4):276-284. https://doi.org/10.1007/s11882-004-0071-8
  24. Wu Z, Uchi H, Morino-Koga S, Shi W, Furue M. Resveratrol inhibition of human keratinocyte proliferation via SIRT1/ARNT/ERK dependent downregulation of aquaporin 3. J Dermatol Sci. 2014;75(1):16-23. https://doi.org/10.1016/j.jdermsci.2014.03.004
  25. Trautmann A, Akdis M, Kleemann D, Altznauer F, Simon HU, Graeve T, et al. T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis. J Clin Invest. 2000;106(1):25-35. https://doi.org/10.1172/JCI9199
  26. Rebane A, Zimmermann M, Aab A, Baurecht H, Koreck A, Karelson M, et al. Mechanisms of IFN-gamma-induced apoptosis of human skin keratinocytes in patients with atopic dermatitis. J Allergy Clin Immunol. 2012;129(5):1297-1306. https://doi.org/10.1016/j.jaci.2012.02.020
  27. Stander S, Steinhoff M. Pathophysiology of pruritis on atopic dermatitis: an overview. Exp Dermatol. 2002;11(1):12-24. https://doi.org/10.1034/j.1600-0625.2002.110102.x
  28. Caglayan Sozmen S, Karaman M, Cilaker Micili S, Isik S, Arikan Ayyildiz Z, Bagriyanik A, et al. Resveratrol ameliorates2,4-dinitrofluorobenzene-induced atopic dermatitis-like lesions through effects on the epithelium. PeerJ. 2016;31:4e1889.
  29. Vercelli D, Geha RS. Regulation of isotype switching. Curr Opin Immunol. 1992;4(6):794-797 https://doi.org/10.1016/0952-7915(92)90064-L
  30. Subhashini, Chauhan PS, SKumari S, Dash D, Singh R. Curcumin inhibits compound 48/80 induced systemic anaphylaxis. American Journal of Life Sciences. 2013;1(4):165-170. https://doi.org/10.11648/j.ajls.20130104.14
  31. Moon PD, Jeong HJ, Kim HM. Down-regulation of thymic stromal lymphopoietin by curcumin. Pharmacol Rep. 2013;65(2):525-531. https://doi.org/10.1016/S1734-1140(13)71029-6
  32. Wakade C, King MD, Laird MD, Alleyne Jr CH, Dhandapani KM. Curcumin attenuates vascular inflammationand cerebral vasospasm after subarachnoid hemorrhage in mice. Antioxid Redox Signal. 2009;11(1):35-45. https://doi.org/10.1089/ars.2008.2056
  33. Lee HC, Headley MB, Iseki M, Ikuta K, Ziegler SF. Cutting edge: Inhibition of NF-kB-mediated TSLP expressionby retinoid X receptor. J Immunol. 2008;181(8):5189-5193. https://doi.org/10.4049/jimmunol.181.8.5189
  34. Lee HC, Ziegler SF. Inducible expression of the proallergic cytokine thymic stromallymphopoietin in airway epithelial cells is controlled by NFkB. Proc Natl AcadSci USA. 2007;104(3):914-919. https://doi.org/10.1073/pnas.0607305104
  35. Jekal SJ, Min BW, Park H. Protective effects of curcumin on CCl4-induced hepatic fibrosis with high fat diet in C57BL/6 mice. Korean J Clin Lab Sci. 2015;47(4):251-258. https://doi.org/10.15324/kjcls.2015.47.4.251
  36. Moosbrugger-Martinz V, Tripp CH, Clausen BE, Schmuth M, Dubrac S. Atopic dermatitis induces the expansion of thymus-derived regulatory T cells exhibiting a Th2-like phenotype in mice. J Cell Mol Med. 2016;20(5):930-938. https://doi.org/10.1111/jcmm.12806

Cited by

  1. Mentha arvensis Essential Oil Exerts Anti-Inflammatory in LPS-Stimulated Inflammatory Responses via Inhibition of ERK/NF-κB Signaling Pathway and Anti-Atopic Dermatitis-like Effects in 2,4-Dinit vol.10, pp.12, 2017, https://doi.org/10.3390/antiox10121941