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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References
- Atopic dermatitis: global epidemiology and risk factors.Ann. Nutr. Metab. 2015; 66: 8-16
- Atopic dermatitis is a serious health problem in Poland. Epidemiology studies based on the ECAP study.Postepy. Dermatol. Alergol. 2015; 32: 1-10
- Atopic dermatitis: an update and review of the literature.Dermatol. Clin. 2007; 25: 605-612
- Atopic dermatitis in children: clinical features, pathophysiology, and treatment.Immunol. Allergy. Clin. N. Am. 2015; 35: 161-183
- Topical corticosteroids in atopic dermatitis.BMJ. 2003; 327: 942-943
- Immunological and molecular targets of atopic dermatitis treatment.Br. J. Dermatol. 2014; 170: 7-11
- Phototherapy in atopic dermatitis.Adv. Exp. Med. Biol. 2017; 996: 279-286
- Atopic dermatitis prevention and treatment.Cutis. 2017; 100 (177;192): 173
- Management of difficult-to-treat atopic dermatitis, T.J. Allergy Clin. Immunol. Pract. 2013; 1: 142-151
- Analysis of pulegone and its enanthiomeric distribution in mint-flavoured food products.Food Addit. Contam. 2005; 22: 197-203
- Calamintha nepeta (L.) Savi and its Main essential oil constituent pulegone: biological activities and chemistry.Molecules. 2017; : 22
- Pharmacological activity of (R)-(+)-pulegone, a chemical constituent of essential oils.Z. Naturforsch. C. 2011; 66: 353-359
- Antihistaminic activity of pulegone on the guinea-pig ileum.J. Pharm. Pharmacol. 1990; 42: 295-296
- Monoterpenes isolated from Minthostachys verticillata (Griseb.) Epling essential oil modulates immediate-type hypersensitivity responses in vitro and in vivo.Planta Med. 2011; 77: 1687-1694
- Schizonepeta tenuifolia inhibits the development of atopic dermatitis in mice.Phytother. Res. 2013; 27: 1131-1135
- Anti-inflammatory activity of Schizonepeta tenuifolia through the inhibition of MAPK phosphorylation in mouse peritoneal macrophages.Am. J. Chin. Med. 2008; 36: 1145-1158
- Atopic dermatitis in animals and people: an update and comparative review.Vet. Sci. 2017; 4
- Lichenified plaques. Scratching exacerbates the pruritic eruption and causes crusted skin markings.Geriatrics. 1999; 54: 63
- Exacerbating factors of itch in atopic dermatitis.Allergol. Int. 2017; 66: 8-13
- Neuropeptides in the skin of patients with atopic dermatitis.Clin. Exp. Dermatol. 1995; 20: 462-467
- Nerve growth factor, pain, itch and inflammation: lessons from congenital insensitivity to pain with anhidrosis.Expert. Rev. Neurother. 2010; 10: 1707-1724
- IgE, mast cells, and eosinophils in atopic dermatitis.Clin. Rev. Allergy. Immunol. 2011; 41: 298-310
- The high-affinity IgE receptor (Fc epsilon RI): from physiology to pathology.Annu. Rev. Immunol. 1999; 17: 931-972
- Microarray analysis of the gene expression profile of HMC-1 mast cells following Schizonepeta tenuifolia briquet treatment.Cell. Immunol. 2012; 277: 58-65
- A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis.Immunol. Today. 1998; 19: 359-361
- Interleukin (IL)-4-independent immunoglobulin class switch to immunoglobulin (Ig) E in the mouse.J. Exp. Med. 1996; 184: 1651-1661
- Role played by Th2 type cytokines in IgE mediated allergy and asthma.Lung. India. 2010; 27: 66-71
- The role of interferon-gamma on immune and allergic responses.Mem. Inst. Oswaldo. Cruz. 2005; 100: 137-144
- 1; New concepts in the pathogenesis of atopic dermatitis.Curr. Opin. Immunol. 2003; 15: 634-638
- TNF-α and;1; Th2 cytokines induce atopic dermatitis-like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents.J. Invest. Dermatol. 2014; 134: 1941-1950
- Targeting the IL-1 family members in skin inflammation.Curr. Opin. Investig. Drugs. 2010; 11: 1211-1220
- IL-6 in inflammation, immunity, and disease.Cold Spring Harb. Perspect. Biol. 2014; 6: a016295
- Topical application with a new NF-kappaB inhibitor improves atopic dermatitis in NC/NgaTnd mice.J. Invest. Dermatol. 2007; 127: 855-863
- NF-kappaB in the regulation of epithelial homeostasis and inflammation.Cell Res. 2011; 21: 146-158
- Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation.Trends. Biochem. Sci. 2005; 30: 43-52
- Regulation and function of NF-kappaB transcription factors in the immune system.Annu. Rev. Immunol. 2009; 27: 693-733
- Regulation of NF-kappa B activation by MAP kinase cascades.Immunobiology. 1997; 198: 35-49
Article info
Publication history
Published online: June 12, 2018
Accepted:
June 8,
2018
Received in revised form:
May 21,
2018
Received:
March 27,
2018
Identification
Copyright
© 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
