The Journal of Pediatrics of Korean Medicine (대한한방소아과학회지)

The Association of Korean Oriental Pediatrics (대한한방소아과학회)
권호 표지
DOI QR코드

DOI QR Code

Hwangnyeonhaedok-tang Extracts Ameliorates Atopic Dermatitis via Epidermal Lipid Barrier Regeneration in NC/Nga Mouse

황련해독탕의 피부지방장벽개선을 통한 Th2 분화조절이 아토피피부염 완화에 미치는 효과

  • Son, Seong Han (School of Korean Medicine, Pusan National University) ;
  • Ahn, Sang Hyun (Department of Anatomy, College of Korean Medicine, Semyung University) ;
  • Park, Sun-Young (Department of Physiology, College of Korean Medicine, Semyung University) ;
  • Kim, Kibong (School of Korean Medicine, Pusan National University)
  • 손성한 (부산대학교 한의학전문대학원) ;
  • 안상현 (세명대학교 한의과대학 해부학교실) ;
  • 박선영 (세명대학교 한의과대학 생리학교실) ;
  • 김기봉 (부산대학교 한의학전문대학원)
  • Received : 2018.07.25
  • Accepted : 2018.08.11
  • Published : 2018.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives Hwangnyeonhaedok-tang is a Korean herbal medical treatment that removes toxic heat, fever and inflammation. The purpose of this study was to investigate the effect of Hwangnyeonhaedok-tang treatment on the relief of atopic dermatitis (AD) through regeneration of skin lipid barrier. Methods Male NC/Nga mice (20 g, 6 week age) were used. Each 10 mice were allocated to the control group (Ctrl), the AD-induced with no treatment group (AE), and the group which induced AD after administering Hwangnyeonhaedok-tang extract (HT). To induce AD-like skin lesions, sodium dodecyl sulfate (SDS) (Sigma-Aldrich, USA) was rubbed on the back of each mouse to remove the lipid lamella of the stratum corneum, and Dermatophagoides (D.) farinae crude extract was applied. HT group was orally administered Hwangnyeonhaedok-tang after induction of AD. IL-4 IL-13, $p-I{\kappa}B$, iNOS, Sudan Black B (SB), loricrin, and filaggrin were observed to confirm the effect. Results In HT group, AD skin score was decreased by 46%. The cytokine IL-4 and IL-13, which can identify Th2 differentiation, was reduced by 73% and 58% each. Anti-inflammatory effects were observed in $p-I{\kappa}B$ and iNOS by 69% and 54%, respectively. Finally, SB showed that the regeneration of the lipid layer and the increase of the regeneration power of loricrin and filaggrin were increased by 437% and 464%, respectively. Conclusions From the study result, we observed that Hwangnyeonhaedok-tang treatment alleviates AD by decreasing skin score, reducing Th2 differentiation, inducing anti-inflammatory, and increasing skin lipid barrier regeneration. Thus, Hwangnyeonhaedok-tang treatment would be considered as an effective AD relieving treatment.

Keywords

References

  1. Engel-Yeger B, Mimouni D, Rozenman D, Shani-Adir A. Sensory processing patterns of adults with atopic dermatitis. J Eur Acad Dermatol Venereol. 2011;25(2): 152-6. https://doi.org/10.1111/j.1468-3083.2010.03729.x
  2. Oh JW, Pyun BY, Choung JT, Ahn KM, Kim CH, Song SW, Son JA, Lee SY, Lee SI. Epidemiological change of atopic dermatitis and food allergy in school-aged children in Korea between 1995 and 2000. J Korean Med Sci. 2004;19(5):716-23. https://doi.org/10.3346/jkms.2004.19.5.716
  3. Jee HM, Kim KW, Kim CS, Sohn MH, Shin DC, Kim KE. Prevalence of asthma, rhinitis and eczema in Korean children using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires. Pediatr Allergy Respir Dis. 2009;19(2): 165-72.
  4. Ahn KM, Kim JH, Kwon HJ, Chae YM, Hahm MI, Lee KJ, Park YM, Lee SY, Han MY, Kim WK. The prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in Korean children: nationwide cross-sectional survey using complex sampling design. J Korean Med Assoc. 2011;54(7):769-78. https://doi.org/10.5124/jkma.2011.54.7.769
  5. Kabashima K. New concept of the pathogenesis of atopic dermatitis: interplay among the barrier, allergy, and pruritus as a trinity. J Dermatol Sci. 2013;70(1):3-11. https://doi.org/10.1016/j.jdermsci.2013.02.001
  6. Rousset F, Robert J, Andary M, Bonnin JP, Souillet G, Chretien I, Brière F, Pene J, de Vries JE. Shifts in interleukin-4 and interferon-gamma production by T cells of patients with elevated serum IgE levels and the modulatory effects of these lymphokines on spontaneous IgE synthesis. J Allergy Clin Immunol. 1991;87(1 Pt1):58-69. https://doi.org/10.1016/0091-6749(91)90213-8
  7. van der Kleij HP, Kraneveld AD, van Houwelingen AH, Kool M, Weitenberg AC, Redegeld FA, Nijkamp FP. Murine model for non-IgE-mediated asthma. Inflammation. 2004;28(3):115-25. https://doi.org/10.1023/B:IFLA.0000039557.33267.65
  8. Park Y. Status of clinical practice on diagnosis and management of atopic dermatitis in Korea: a questionnaire survey of physicians. Allergy Asthma Respir Dis. 2013;1(3):257-65. https://doi.org/10.4168/aard.2013.1.3.257
  9. Callen J, Chamlin S, Eichenfield LF, Ellis C, Girardi M, Goldfarb M, Hanifin J, Lee P, Margolis D, Paller AS, Piacquadio D, Peterson W, Kaulback K, Fennerty M, Wintroub BU. A systematic review of the safety of topical therapies for atopic dermatitis. Br J Dermatol. 2007;156(2):203-21. https://doi.org/10.1111/j.1365-2133.2006.07538.x
  10. Pariser D. Topical corticosteroids and topical calcineurin inhibitors in the treatment of atopic dermatitis: focus on percutaneous absorption. Am J Ther. 2009;16(3):264-73. https://doi.org/10.1097/MJT.0b013e31818a975c
  11. Im GM, Jeong HW, Kim HS, Jeong WY. Oriental medical approach on the allergic disease. J Physiol Pathol Korean Med. 2002;16(5):831-9.
  12. Schneider L, Tilles S, Lio P, Boguniewicz M, Beck L, LeBovidge J, Novak N, Bernstein D, Blessing-Moore J, Khan D, Lang D, Nicklas R, Oppenheimer J, Portnoy J, Randolph C, Schuller D, Spector S, Tilles S, Wallace D. Atopic dermatitis: a practice parameter update 2012. J Allergy Clin Immunol. 2013;131(2):295-9. https://doi.org/10.1016/j.jaci.2012.12.672
  13. Ki HP, Jang SI, Yun YG. Ameliorative effects of Hwangnyeonhaedok-tang on atopic dermatitis. Kor J Herbology. 2013;21(1):80-90.
  14. Kim BA, Kim MS, Kang BM, Byeon SH, Park IH, Park JH, Jung JW, Ahn EM, Jung HA, Jang JH, Bae W, Lee HY, Choi PN, Park CI. Inhibitory studies of Hwangryunhaedok-tang on development of atopic dermatitis in Nc/Nga mice. Kor J Herbology. 2008;23(2): 59-65.
  15. Wahlgren CF. Itch and atopic dermatitis: an overview. J Dermatol. 1999;26(11):770-9. https://doi.org/10.1111/j.1346-8138.1999.tb02090.x
  16. Baron ED, Barzilai D, Johnston G, Kawashima M, Takigawa M, Nakagawa H, Graham-Browh R, Stevens SR. Atopic dermatitis management: comparing the treatment patterns of dermatologists in Japan, U.S.A. and U.K. Br J Dermatol. 2002;147(4):710-5. https://doi.org/10.1046/j.1365-2133.2002.04895.x
  17. Drake LA, Fallon JD, Sober A. Relief of pruritus in patients with atopic dermatitis after treatment with topical doxepin cream. The Doxepin Study Group. J Am Acad Dermatol. 1994;31(4):613-6. https://doi.org/10.1016/S0190-9622(94)70225-X
  18. Bonnel RA, La Grenade L, Karwoski CB, Beitz JG. Allergic contact dermatitis from topical doxepin: Food and Drug Administration's postmarketing surveillance experience. J Am Acad Dermatol. 2003;48(2):294-6. https://doi.org/10.1067/mjd.2003.46
  19. Lassus A. Clinical comparison of alclometasone dipropionate cream 0.05% with hydrocortisone butyrate cream 0.1% in the treatment of atopic dermatitis in children. J Int Med Res. 1983;11(5):315-9. https://doi.org/10.1177/030006058301100512
  20. Steinert PM, Cantieri JS, Teller DC, Lonsdale-Eccles JD, Dale BA. Characterization of a class of cationic proteins that specifically interact with intermediate filaments. Proc Natl Acad Sci USA. 1981;78(7):4097-101. https://doi.org/10.1073/pnas.78.7.4097
  21. Kim HJ, Shin JU, Lee KH. Atopic dermatitis and skin barrier dysfunction. Allergy Asthma Respir Dis. 2013;1(1):20-8. https://doi.org/10.4168/aard.2013.1.1.20
  22. Steinert PM, Marekov LN. The proteins elafin, filaggrin, keratin intermediate filaments, loricrin, and small proline-rich proteins 1 and 2 are isodipeptide cross-linked components of the human epidermal cornified cell envelope. J Biol Chem. 1995;270(30):17702-11. https://doi.org/10.1074/jbc.270.30.17702
  23. Steinett PM, Marekov LN. Direct evidence that involucrin is a major early isopeptide cross-linked component of the keratinocyte cornified cell envelope. J Biol Chem. 1997;272(3):2021-30. https://doi.org/10.1074/jbc.272.3.2021
  24. Kim BE, Leung DY, Boguniewicz M, Howell MD. Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6. Clin Immunol. 2008;126(3):332-7. https://doi.org/10.1016/j.clim.2007.11.006
  25. Smith FJ, Irvine AD, Terron-Kwiatkowski A, Sandilands A, Campbell LE, Zhao Y, Liao H, Evans AT, Goudie DR, Lewis-Jones S, Arseculeratne G, Munro CS, Sergeant A, O'Regan G, Bale SJ, Compton JG, DiGiovanna JJ, Presland RB, Fleckman P, McLean WH. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet. 2006;38(3):337-42. https://doi.org/10.1038/ng1743
  26. O'Regan GM, Irvine AD. The role of filaggrin in the atopic diathesis. Clin Exp Allergy. 2010;40(7):965-72. https://doi.org/10.1111/j.1365-2222.2010.03522.x
  27. Cha HY, Ahn SH, Cheon JH, Park IS, Kim JT, Kim K. Hataedock treatment has preventive therapeutic effects in atopic dermatitis-induced NC/Nga mice under high-fat diet conditions. Evid Based Complement Alternat Med. 2016;2016:1739760.
  28. Bruch-Gerharz D, Fehsel K, Suschek C, Michel G, Ruzicka T, Kolb-Bachofen V. A proinflammatory activity of interleukin 8 in human skin: expression of the inducible nitric oxide synthase in psoriatic lesions and cultured keratinocytes. J Exp Med. 1996;184(5):2007-12. https://doi.org/10.1084/jem.184.5.2007
  29. Bruch-Gerharz D, Ruzicka T, Kolb-Bachofen V. Nitric oxide and its implications in skin homeostasis and disease - a review. Arch Dermatol Res. 1998;290(12):643-51. https://doi.org/10.1007/s004030050367
  30. Hatano Y, Terashi H, Arakawa S, Katagiri K. Interleukin-4 suppresses the enhancement of ceramide synthesis and cutaneous permeability barrier functions induced by tumor necrosis factor-${\alpha}$ and interferon-${\gamma}$ in human epidermis. J Invest Dermatol. 2005;124(4): 786-92. https://doi.org/10.1111/j.0022-202X.2005.23651.x
  31. Albanesi C, Fairchild HR, Madonna S, Scarponi C, De Pita O, Leung DY, Howell MD. IL-4 and IL-13 negatively regulate TNF-${\alpha}$-and IFN-${\gamma}$-induced ${\beta}$-defensin expression through STAT-6, suppressor of cytokine signal- ing (SOCS)-1, and SOCS-3. J Immunol. 2007;179(2): 984-92. https://doi.org/10.4049/jimmunol.179.2.984
  32. Kubo A, Nagao K, Amagai M. Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases. J Clin Invest. 2012;122(2):440-7. https://doi.org/10.1172/JCI57416
  33. Chung HY, Cesari M, Anton S, Marzetti E, Giovannini S, Seo AY, Carter C, Yu BP, Leeuwenburgh C. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev. 2009;8(1):18-30. https://doi.org/10.1016/j.arr.2008.07.002
  34. Baeuerle PA, Baltimore D. NF-kappa B: ten years after. Cell. 1996;87(1):13-20. https://doi.org/10.1016/S0092-8674(00)81318-5
  35. Aktan F. iNOS-mediated nitric oxide production and its regulation. Life Sci. 2004;75(6):639-53. https://doi.org/10.1016/j.lfs.2003.10.042
  36. Aktan F, Henness S, Roufogalis BD, Ammit AJ. Gypenosides derived from Gynostemma pentaphyllum suppress NO synthesis in murine macrophages by inhibiting iNOS enzymatic activity and attenuating $NF-{\kappa}B$-mediated iNOS protein expression. Nitric Oxide. 2003;8(4):235-42. https://doi.org/10.1016/S1089-8603(03)00032-6