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

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 mu M) 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 DNCBinduced AD. The levels of IL-4, IFN-gamma, IL-6, TNF-alpha and IL-beta in dorsal skin of PLG-treated group were lower than those in the control group. PLG inhibited the phosphorylation of MAPKs, as well as IKB alpha degradation and NF-kappa B activation. Conclusions: PLG attenuated the symptoms of AD by suppressing cytokines production, the phosphorylation of MAPKs and the activation of NF-kappa B signaling. These data suggest that PLG may be an effective natural compound for the treatment of inflammatory skin diseases. (C) 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.