Evaluation of the Atopic Dermatitis-mitigating and Anti-inflammatory Effects of Kyung Hee Allergic Disease Herbal Formula (KAHF)

  • Koh, Duck-Jae (Department of Pediatrics, Hospital of Oriental Medicine, Kyung Hee Medical Center) ;
  • Kim, Yang-Hee (Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University) ;
  • Kim, Deog-Gon (Department of Pediatrics, Hospital of Oriental Medicine, Kyung Hee Medical Center) ;
  • Lee, Jin-Yong (Department of Pediatrics, Hospital of Oriental Medicine, Kyung Hee Medical Center) ;
  • Lee, Kyung-Tae (Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University)
  • 발행 : 2008.12.31

초록

The purpose of this study was to investigate the effects of Kyung Hee Allergic Disease Herbal Formula (KAHF) on atopic dermatitis (AD) and its mode of action. Our clinical study showed KAHF reduced Severity Scoring of Atopic Dermatitis (SCORAD) indexes and subjective symptom scores. In parallel, the decreased levels of interferon (IFN)-$\gamma$ and interleukin (IL)-5 in serum, which contributed to its AD-mitigating effect was observed. To reveal the underlying mechanisms of KAHF in AD, its anti-inflammatory effect on lipopolysaccharide (LPS)-induced responses in RAW 264.7 cells was examined. KAHF was found to significantly inhibit the productions of nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and IL-$1{\beta}$ in LPS-stimulated RAW 264.7 macrophages. Consistently, KAHF potently inhibited protein and mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, KAHF inhibited LPS-induced activation of nuclear factor (NF)-$\kappa}B$. Taken together, our data suggest that KAHF has a beneficial effect on several eicosanoid-related skin inflammations, such as atopic dermatitis.

키워드

참고문헌

  1. Cooper KD. Atopic dermatitis: Recent trends in pathogenesis and therapy. J. Invest. Dermatol. 102: 128-137 (1994) https://doi.org/10.1111/1523-1747.ep12371746
  2. Friedlander SF. Corticosteroids: Options in the era of steroid-sparing therapy. J. Am. Acad. Dermatol. 53: S50-S58 (2005) https://doi.org/10.1016/j.jaad.2005.04.030
  3. Shekelle PG, Morton SC, Suttorp MJ, Buscemi N, Friesen C. Challenges in systematic reviews of complementary and alternative medicine topics. Ann. Intern. Med. 142: 1042-1047 (2005) https://doi.org/10.7326/0003-4819-142-12_Part_2-200506211-00003
  4. Zhang W, Leonard T, Bath-Hextall F, Chambers CA, Lee C, Humphreys R, Williams HC. Chinese herbal medicine for atopic eczema. Cochrane DB Syst. Rev. 4: CD002291 (2004)
  5. Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J. Clin. Invest. 113: 651-657 (2004) https://doi.org/10.1172/JCI21060
  6. Wardlaw AJ, Moqbel R, Kay AB. Eosinophils: Biology and role in disease. Immunology 60: 151-266 (1995) https://doi.org/10.1016/S0065-2776(08)60586-6
  7. Mosmann TR, Coffman RL. TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol. 7: 145-173 (1989) https://doi.org/10.1146/annurev.iy.07.040189.001045
  8. Herz U, Bunikowski R, Renz H. Role of T cells in atopic dermatitis. Int. Arch. Allergy Imm. 115: 179-190 (1998) https://doi.org/10.1159/000023899
  9. Sanderson CJ. Interleukin-5, eosinophils, and disease. Blood 79: 3101-3109 (1992)
  10. O'Garra A. Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 8: 275-283 (1998) https://doi.org/10.1016/S1074-7613(00)80533-6
  11. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm. Venereol. 2: 44-47 (1980)
  12. Stalder JF, Atherton T. Severity scoring of atopic dermatitis: The SCORAD index. Consensus report of the european task force on atopic dermatitis. Dermatology 186: 23-31 (1993) https://doi.org/10.1159/000247298
  13. Won JH, Im HT, Kim YH, Yun KJ, Park HJ, Choi JW, Lee KT. Anti-inflammatory effect of buddlejasaponin IV through the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via the NF-kappaB inactivation. Brit. J. Pharmacol. 148: 216-225 (2006) https://doi.org/10.1038/sj.bjp.0706718
  14. Baeuerle PA, Baltimore D. $NF-{\kappa}B:$ Ten years after. Cell 87: 13-20 (1996) https://doi.org/10.1016/S0092-8674(00)81318-5
  15. Nolan GP, Ghosh S, Liou HC, Tempst P, Baltimore D. DNA binding and I kappa B inhibition of the cloned p65 subunit of NF-kappaB, a rel-related polypeptide. Cell 64: 961-969 (1991) https://doi.org/10.1016/0092-8674(91)90320-X
  16. Beck LA, Leung DY. Allergen sensitization through the skin induces systemic allergic responses. J. Allergy Clin. Immun. 106: S258-S263 (2000) https://doi.org/10.1067/mai.2000.110159
  17. Grewe M, Gyufko K, Schopf E, Krutmann J. Lesional expression of interferon-gamma in atopic eczema. Lancet 343: 25-26 (1994) https://doi.org/10.1016/S0140-6736(94)90879-6
  18. Grewe M, Schopf E, Thepen T, Ruzicka T. A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis. Immunol. Today 19: 359-361 (1998) https://doi.org/10.1016/S0167-5699(98)01285-7
  19. Kimura M, Tsuruta S, Yoshida T. Correlation of house dust mite-specific lymphocyte proliferation with IL-5 production, eosinophilia, and the severity of symptoms in infants with atopic dermatitis. J. Allergy Clin. Immun. 101: 84-89 (1998) https://doi.org/10.1016/S0091-6749(98)70197-6
  20. Kimura M, Tsuruta S, Yoshida T. Unique profile of IL-4 and IFN-gamma production by peripheral blood mononuclear cells in infants with atopic dermatitis. J. Allergy Clin. Immun. 102: 238-244 (1998) https://doi.org/10.1016/S0091-6749(98)70092-2
  21. Thepen T, Bihari IC, van Wichen DF, van Reijse FC. Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial Th2 response to a Th1 response in situ: An immunocytochemical study. J. Allergy Clin. Immun. 97: 828-837 (1996) https://doi.org/10.1016/S0091-6749(96)80161-8
  22. Novak N, Kraft S, Bieber T. Unraveling the mission of $Fc{\varepsilon}RI$ on antigen-presenting cells. J. Allergy Clin. Immun. 111: 38-44 (2003) https://doi.org/10.1067/mai.2003.2
  23. Spergel JM, Mizoguchi E, Oettgen H, Bhan AK, Geha RS. Roles of Thl and Th2 cytokines in a murine model of allergic dermatitis. J. Clin. Invest. 103: 1103-1111 (1999) https://doi.org/10.1172/JCI5669
  24. Smart JM, Kemp AS. Increased Th1 and Th2 allergen-induced cytokine responses in children with atopic disease. Clin. Exp. Allergy 32: 796-802 (2002) https://doi.org/10.1046/j.1365-2222.2002.01391.x
  25. Ohmen JD, Hanifin JM, Nickoloff BJ. Overexpression of IL-10 in atopic dermatitis. Contrasting cytokine patterns with delayed-type hypersensitivity reactions. Immunology 154: 1956-1963 (1995)
  26. Hamid Q, Boguniewicz M, Leung DY. Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J. Clin. Invest. 94: 870-876 (1994) https://doi.org/10.1172/JCI117408
  27. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S. A Toll-like receptor recognizes bacterial DNA. Nature 408: 740-745 (2000) https://doi.org/10.1038/35047123
  28. Aral M, Arican O, Gul M, Sasmaz S, Kocturk SA, Kastal U, Ekerbicer HC. The relationship between serum levels of total IgE, IL-18, IL-12, IFN-gamma, and disease severity in children with atopic dermatitis. Mediat. Inflamm. 4: 73098 (2006)
  29. Prehn A, Seger RA, Faber J, Torresani T, Molinari L, Gerber A, Sennhauser FH. The relationship of serum-eosinophil cationic protein and eosinophil count to disease activity in children with bronchial asthma. Pediatr. Allergy Immu. 4: 197-203 (1998)
  30. Bratton DL, Hamid Q, Boguniewicz M, Doherty DE, Kailey JM, Leung DY. Granulocyte macrophage colony-stimulating factor contributes to enhanced monocyte survival in chronic atopic dermatitis. J. Clin. Invest. 95: 211-218 (1995) https://doi.org/10.1172/JCI117642
  31. Bratton DL, May KR, Kailey JM, Doherty DE, Leung DY. Staphylococcal toxic shock syndrome toxin-1 inhibits monocyte apoptosis. J. Allergy Clin. Immun. 103: 895-900 (1999) https://doi.org/10.1016/S0091-6749(99)70435-5
  32. Roper RL, Brown DM, Phipps RP. Prostaglandin $E_2$ promotes B lymphocyte Ig isotype switching to IgE. Immunology 154: 162-170 (1995)
  33. Roper RL, Phipps RP. Prostaglandin $E_2$ regulation of the immune response. Adv. Prostag. Thromb. L. 22: 101-111 (1994)
  34. Taniuchi S, Kojima T, Kobayashi Y. Increased serum nitrate levels in infants with atopic dermatitis. Allergy 56: 693-695 (2001) https://doi.org/10.1034/j.1398-9995.2001.00131.x
  35. Wei XQ, Charles IG, Smith A, Ure J, Feng GJ, Huang FP, Xu D, Muller W, Moncada S, Liew FY. Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 375: 408-411 (1995) https://doi.org/10.1038/375408a0
  36. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood 87: 2095-2147 (1996)
  37. Hunter CA, Chizzonite R, Remington JS. IL-1 beta is required for IL-12 to induce production of IFN-gamma by NK cells. A role for IL-1 beta in the T cell-independent mechanism of resistance against intracellular pathogens. Immunology 155: 4347-4354 (1995)
  38. Dajee M, Muchamuel T, Schryver B, Oo A, Alleman-Sposeto J, De Vry CG, Prasad S, Ruhrmund D, Shyamsundar R, Mutnick D, Mai K, Le T, Parham C, Zhang J, Komuves L, Colby T, Hudak S, McEvoy LM, Ehrhardt RO. Blockade of experimental atopic dermatitis via topical NF-kappaB decoy oligonucleotide. J. Invest. Dermatol. 126: 1792-1803 (2006) https://doi.org/10.1038/sj.jid.5700307
  39. Barnes PJ, Karin M. Nuclear factor-kappaB: A pivotal transcription factor in chronic inflammatory diseases. New Engl. J. Med. 336: 1066-1071 (1997) https://doi.org/10.1056/NEJM199704103361506
  40. Chung HS, Kang M, Cho C, Park S, Kim H, Yoon YS, Kang J, Shin MK, Hong MC, Bae H. Inhibition of lipopolysaccharide and interferon-gamma-induced expression of inducible nitric oxide synthase and tumor necrosis factor-alpha by Lithospermi radix in mouse peritoneal macrophages. J. Ethnopharmacol. 102: 412-417 (2005) https://doi.org/10.1016/j.jep.2005.06.028
  41. Staniforth V, Wang SY, Shyur LF, Yang NS. Shikonins, phytocompounds from Lithospermum erythrorhizon, inhibit the transcriptional activation of human tumor necrosis factor alpha promoter in vivo. J. Biol. Chem. 279: 5877-5885 (2004) https://doi.org/10.1074/jbc.M309185200
  42. Shin KM, Kim YH, Park WS, Kang I, Ha J, Choi JW, Park HJ, Lee KT. Inhibition of methanol extract from the fruits of Kochia scoparia on lipopolysaccharide-induced nitric oxide, prostaglandin $E_2$, and tumor necrosis $factor-{\alpha}$ production from murine macrophage RAW 264.7 Cells. Biol. Pharm. Bull. 27: 538-543 (2004) https://doi.org/10.1248/bpb.27.538
  43. Matsuda H, Dai Y, Ido Y. Studies on Kochiae fructus. III. Antinociceptive and antiinflammatory effects of 70% ethanol extract and its component, momordin Ic from dried fruits of Kochia scoparia L. Biol. Pharm. Bull. 20: 1086-1091 (1997) https://doi.org/10.1248/bpb.20.1086
  44. Matsuda H, Dai Y, Ido Y, Ko S, Yoshikawa M, Kubo M. Studies on Kochiae fructus. IV. Anti-allergic effects of 70% ethanol extract and its component, momordin Ic from dried fruits of Kochia scoparia L. Biol. Pharm. Bull. 20: 1165-1170 (1997) https://doi.org/10.1248/bpb.20.1165
  45. Sucher NJ. Insights from molecular investigations of traditional Chinese herbal stroke medicines: Implications for neuroprotective epilepsy therapy. Epilepsy Behav. 8: 350-362 (2006) https://doi.org/10.1016/j.yebeh.2005.11.015
  46. Wong HC, Wong JK, Wong NY. Chinese herbal medicine for irritable bowel syndrome. J. Am. Med. Assoc. 282: 1036-1037 (1999)
  47. Kaptchuk TJ. Chinese herbal medicine for irritable bowel syndrome. J. Am. Med. Assoc. 282: 1035-1036 (1999) https://doi.org/10.1001/jama.282.11.1035