Molecular Biology Reports

, Volume 40, Issue 3, pp 2541–2548 | Cite as

A (S)-(+)-decursin derivative, (S)-(+)-3-(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo-3,4-dihydro-2H,8H-pyrano[3,2-g]-chromen-3-yl-ester, attenuates the development of atopic dermatitis-like lesions in NC/Nga mice

  • In Sik Kim
  • Dong-Hee Kim
  • Chi-Young Yun
  • Ji-Sook Lee


(S)-(+)-decursin is a biological coumarin compound isolated from Angelica gigas Nakai. (S)-(+)-decursin and its analogue have a variety of pharmacological activities. In the present study, the anti-inflammatory effect of a (S)-(+)-decursin derivative, (S)-(+)-3-(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo-3,4-dihydro-2H,8H-pyrano [3,2-g]-chromen-3-yl-ester (Compound 6, C6), on in vitro and in vivo atopic dermatitis was investigated. C6 suppressed the secretion of IL-6, IL-8, and monocyte chemotactic protein-1 increase by the house dust mite extract in the eosinophilic leukemia cell line and THP-1 cells. C6 inhibited the production of TARC, IL-6, and IL-8 increase by IFN-γ and TNF-α in the human keratinocyte cell line. In the in vivo experiment, NC/Nga mice were sensitized to 2,4-dinitrochlorobenzene, and then C6 or dexamethasone (Dex) were orally and dorsally administered for three weeks. C6 treatment reduced the skin severity score compared with that of the control group. C6 inhibited the thickening of the epidermis and inflammatory cell infiltration into the dermis by evaluating the histological examination. The serum immunoglobulin E (IgE) level decreased in the C6–treated group compared with that of the control group. The inhibitory effect of C6 on IgE concentration was similar to that of Dex. The levels of IL-4, IL-5, IL-13, and eotaxin increased after treatment with concanavalin A in mouse splenocytes. The cytokine levels of the C6-treated group were lower than those of the control group. Taken together, C6 may attenuate atopic dermatitis-like lesions through its anti-inflammatory effect, such as inhibition of IgE and inflammatory cytokines, and it may be valuable as a therapeutic drug for the treatment of atopic dermatitis.


(S)-(+)-decursin derivative Atopic dermatitis Anti-inflammatory effect IgE 



Atopic dermatitis


(S)-(+)-3-(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo-3,4-dihydro -2H,8H-pyrano[3,2-g]-chromen-3-yl-ester


Fetal bovine serum


Immunoglobulin E


Monocyte chemotactic protein-1




Protein kinase C


Extracellular-signal-regulated kinase



This work was supported by the RIC program of Ministry of Knowledge Economy (No.TBRC 05-06-02) in Daejeon University.

Supplementary material

11033_2012_2339_MOESM1_ESM.ppt (71 kb)
Supplementary material 1 (PPT 71 kb)


  1. 1.
    Bonness S, Bieber T (2007) Molecular basis of atopic dermatitis. Curr Opin Allergy Clin Immunol 7:382–386PubMedCrossRefGoogle Scholar
  2. 2.
    Bieber T (2008) Atopic dermatitis. N Engl J Med 358:1483–1494PubMedCrossRefGoogle Scholar
  3. 3.
    Tokura Y (2010) Extrinsic and intrinsic types of atopic dermatitis. J Dermatol Sci 58:1–7PubMedCrossRefGoogle Scholar
  4. 4.
    Jujo K, Renz H, Abe J, Gelfand EW, Leung DY (1992) Decreased interferon-γ and increased interleukin-4 production in atopic dermatitis promotes IgE synthesis. J Allergy Clin Immunol 90:323–331PubMedCrossRefGoogle Scholar
  5. 5.
    Gavino AC, Needham GR, High WA (2008) Atopic dermatitis, patch testing, and house dust mites. Dermatitis 19:121–128PubMedGoogle Scholar
  6. 6.
    Yang EJ, Song GY, Lee JS, Yun CY, Kim IS (2009) A novel (S)-(+)-decursin derivative, (S)-(+)-3-(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo-3,4-dihydro-2H,8H-pyrano[3,2-g]chromen-3-yl-ester, inhibits ovalbumin-induced lung inflammation in a mouse model of asthma. Biol Pharm Bull 32:444–449PubMedCrossRefGoogle Scholar
  7. 7.
    Li L, Li W, Jung SW, Lee YW, Kim YH (2011) Protective effects of decursin and decursinol angelate against amyloid β-protein-induced oxidative stress in the PC12 cell line: the role of Nrf2 and antioxidant enzymes. Biosci Biotechnol Biochem 75:434–442PubMedCrossRefGoogle Scholar
  8. 8.
    Son SH, Park KK, Park SK, Kim YC, Kim YS, Lee SK, Chung WY (2011) Decursin and decursinol from Angelica gigas inhibit the lung metastasis of murine colon carcinoma. Phytother Res 25:959–964PubMedCrossRefGoogle Scholar
  9. 9.
    Lee JS, Kim IS, Ryu JS, Yun CY (2008) House dust mite, Dermatophagoides pteronissinus increases expression of MCP-1, IL-6, and IL-8 in human monocytic THP-1 cells. Cytokine 42:365–371PubMedCrossRefGoogle Scholar
  10. 10.
    Lee JS, Kim IS, Ryu JS, Yun CY (2009) House dust mite, Dermatophagoides pteronissinus increases expression of MCP-1, IL-6, and IL-8 in human eosinophilic leukemia EoL-1 cells. Animal Cells Systems 13:391–397CrossRefGoogle Scholar
  11. 11.
    Matsuda H, Watanabe N, Geba GP, Sperl J, Tsudzuki M, Hiroi J, Matsumoto M, Ushio H, Saito S, Askenase PW, Ra C (1997) Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice. Int Immunol 9:461–466PubMedCrossRefGoogle Scholar
  12. 12.
    Matsumoto M, Itakura A, Tanaka A, Fujisawa C, Matsuda H (2001) Inability of IL-12 to down-regulate IgE synthesis due to defective production of IFN-gamma in atopic NC/Nga mice. J Immunol 167:5955–5962PubMedGoogle Scholar
  13. 13.
    Guttman-Yassky E, Nograles KE, Krueger JG (2011) Contrasting pathogenesis of atopic dermatitis and psoriasis–part II: immune cell subsets and therapeutic concepts. J Allergy Clin Immunol 127:1420–1432PubMedCrossRefGoogle Scholar
  14. 14.
    Hirano T (1998) Interleukin 6 and its receptor: ten years later. Int Rev Immunol 16:249–284PubMedCrossRefGoogle Scholar
  15. 15.
    Rossi D, Zlotnik A (2000) The biology of chemokines and their receptors. Annu Rev Immunol 18:217–242PubMedCrossRefGoogle Scholar
  16. 16.
    Shakoory B, Fitzgerald SM, Lee SA, Chi DS, Krishnaswamy G (2004) The role of human mast cell-derived cytokines in eosinophil biology. J Interferon Cytokine Res 24:271–281PubMedCrossRefGoogle Scholar
  17. 17.
    Novak N (2009) New insights into the mechanism and management of allergic diseases: atopic dermatitis. Allergy 64:265–275PubMedCrossRefGoogle Scholar
  18. 18.
    Kim SY, Sohn EJ, Kim DW, Jeong HJ, Kim MJ, Kang HW, Shin MJ, Ahn EH, Kwon SW, Kim YN, Kwon HJ, Kim TY, Lee KS, Park J, Eum WS, Choi SY (2011) Transduced PEP-1-FK506BP ameliorates atopic dermatitis in NC/Nga mice. J Invest Dermatol 131:1477–1485PubMedCrossRefGoogle Scholar
  19. 19.
    Cho YS, Kim CH, Surh JH, Kang NS, Yoo SE, Cheon HG (2010) Identification of 4-[4-(4-fluoro-phenyl)-thiazol-2-ylamino]-2,6-dimethyl-phenol (KR-33749) as an inhibitor of 5-lipoxygenase with potent antiinflammatory activity. Pharmacology 86:65–72PubMedCrossRefGoogle Scholar
  20. 20.
    Im LR, Ahn JY, Kim JH, Xin M, Kwon SU, Kim YK, Kim DK, Lee YM (2011) Inhibitory effect of kyungohkgo in the development of 2,4-dinitrochlorobenzene-induced atopic dermatitis in Nc/Nga mice. Arch Pharm Res 34:317–321PubMedCrossRefGoogle Scholar
  21. 21.
    Lee JS, Kim IS, Ryu JS, Kim JH, Kim JS, Kim DH, Yun CY (2012) The inhibitory effect of Duchesnea chrysantha extract on the development of atopic dermatitis-like lesions by regulating IgE and cytokine production in Nc/Nga mice. Phytother Res 26:284–290PubMedCrossRefGoogle Scholar
  22. 22.
    Romagnani S (1994) Lymphokine production by human T cells in disease states. Annu Rev Immunol 12:227–257PubMedCrossRefGoogle Scholar
  23. 23.
    Sicherer SH, Leung DY (2010) Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2009. J Allergy Clin Immunol 125:85–97PubMedCrossRefGoogle Scholar
  24. 24.
    Yuk JE, Woo JS, Yun CY, Lee JS, Kim JH, Song GY, Yang EJ, Hur IK, Kim IS (2007) Effects of lactose-beta-sitosterol and beta-sitosterol on ovalbumin-induced lung inflammation in actively sensitized mice. Int Immunopharmacol 7:1517–1527PubMedCrossRefGoogle Scholar
  25. 25.
    Yuan XY, Ma HM, Li RZ, Wang RY, Liu W, Guo JY (2011) Topical application of aloperine improves 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice. Eur J Pharmacol 658:263–269PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • In Sik Kim
    • 1
  • Dong-Hee Kim
    • 2
  • Chi-Young Yun
    • 3
  • Ji-Sook Lee
    • 4
  1. 1.Department of Biomedical Laboratory Science, School of MedicineEulji UniversityDaejeonRepublic of Korea
  2. 2.Department of Pathology, College of Oriental MedicineDaejeon UniversityDaejeonRepublic of Korea
  3. 3.Department of BiologyDaejeon UniversityDaejeonRepublic of Korea
  4. 4.Department of Clinical Laboratory ScienceWonkwang Health Science UniversityIksanRepublic of Korea

Personalised recommendations