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(R)-(+)-pulegone suppresses allergic and inflammation responses on 2,4-dinitrochlorobenzene-induced atopic dermatitis in mice model

  • You Yeon Choi
    Affiliations
    Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
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  • Mi Hye Kim
    Affiliations
    Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
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  • Haesu Lee
    Affiliations
    Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
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  • Si Yeon Jo
    Affiliations
    Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
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  • Woong Mo Yang
    Correspondence
    Corresponding author at: Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
    Affiliations
    Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
    Search for articles by this author

      Highlights

      • (R)-(+)-pulegone (PLG) decreases the skin thickness in DNCB-induced atopic dermatitis (AD) mice.
      • PLG suppresses scratching behavior, serum IgE levels and the number of mast cells in dermis.
      • PLG inhibits IL-4, IFN-γ, IL-6, IL-1β and TNF-α in DNCB-induced AD mice.
      • PLG regulates NF-κB and MAPKs signaling pathways in DNCB-induced AD mice.

      Abstract

      Background

      (R)-(+)-pulegone (PLG), a biotransformation of monoterpene ketones, is one of essential oils of Labiatae family. Although PLG was reported to have anti-inflammatory and anti-histamine effects, the therapeutic effects of PLG on atopic dermatitis (AD) have not been reported yet.

      Objective

      This study investigated the anti-AD effects and underlying mechanisms of PLG in AD-induced mice.

      Methods

      BALB/c male mice were challenged with 2, 4-dinitrochlorobenzene (DNCB, 1%) to induce AD. After 4 days of rest, PLG (0.1, 1 and 10 μM) were topically applied to dorsal skin for 2 weeks with secondary elicitation using 0.5% DNCB. Histological changes were identified by H&E staining and mast cells were evaluated by toluidine blue staining. Pro-inflammatory cytokines and serum IgE levels were analyzed by ELISA. Inflammatory mediators were measured by western blotting assay.

      Results

      Topical treatment with PLG significantly suppressed skin thickness and scratching behavior compared with control group. Expression of nerve growth factor was also decreased by PLG treatment. PLG administration decreased serum IgE levels and the number of mast cells in mice model of DNCB-induced AD. The levels of IL-4, IFN-γ, IL-6, TNF-α and IL-1β in dorsal skin of PLG-treated group were lower than those in the control group. PLG inhibited the phosphorylation of MAPKs, as well as IκBα degradation and NF-κB activation.

      Conclusions

      PLG attenuated the symptoms of AD by suppressing cytokines production, the phosphorylation of MAPKs and the activation of NF-κB signaling. These data suggest that PLG may be an effective natural compound for the treatment of inflammatory skin diseases.

      Keywords

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