Sclareol attenuates the development of atopic dermatitis induced by 2,4-dinitrochlorobenzene in mice

Abstract

Context: Atopic dermatitis is a common chronic inflammatory skin disease affecting up to 20% of children and 1% of adults worldwide. Treatment of atopic dermatitis include corticosteroids and immunosuppressants, such as calcineurin inhibitors and methotrexate. However, these treatments often bring about adverse effects including skin atrophy, osteoporosis, skin cancer, and metabolic syndrome.

Objective: In this study, we evaluated the therapeutic effects and mechanisms of sclareol, a natural diterpene, on atopic dermatitis (AD)-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) in mice.

Materials and methods: To evaluate the effect of sclareol in vivo model, BALB/c mice were repeatedly injected intraperitoneally with sclareol (50 and 100 mg/kg) in 2,4-dinitrochlorobenzene (DNCB)-induced AD-like murine model. Major assays were enzyme-linked immunosorbent assay, histological analysis, flow cytometry, western blot analysis.

Results: Intraperitoneal administration of sclareol (50 and 100 mg/kg) significantly attenuated AD-like symptoms, such as serum IgE levels, epidermal/dermal hyperplasia, and the numbers of infiltrated mast cells. In addition, systemic sclareol treatments reduced local pro-inflammatory cytokine concentrations, including IL-6, IL-1b, TNF-a, IL-4, IFN-g, and IL-17A, on AD-like lesions. Furthermore, we demonstrated that sclareol also suppressed T cell activation and the capability of cytokine productions (IFN-g, IL-4 and IL-17A) in response to DNCB stimulation. By examining the skin homogenate, we found that sclareol inhibited the AD-like severity likely through suppressions of both NF-kB translocation and phosphorylation of the MAP kinase pathway.

Discussion and conclusions: Cumulatively, our results indicate that sclareol induced anti-inflammatory effects against the atopic dermatitis elicited by DNCB. Thus, sclareol is worth of being further evaluated for its potential therapeutic benefits for the clinical treatment of AD.

Keywords:

• Sclareol
• atopic dermatitis (AD)
• 2,4-dinitrochlorobenzene (DNCB)
• IgE
• cytokines
• T cells

Disclosure statement

The authors report no declarations of interest.

Additional information

Funding

This study was financially supported by the iEGG and Animal Biotechnology Center from The Feature Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education [MOE-107-S-0023-E] in Taiwan.