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Sclareol attenuates the development of atopic dermatitis induced by 2,4-dinitrochlorobenzene in mice
Po-Chang Wu1, Wen-Ho Chuo2, Shih-Chao Lin3
1a Rheumatology and Immunology Center, China Medical University Hospital , Taichung , Taiwan.
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.
Insights
Sclareol, a natural compound, effectively reduced atopic dermatitis (AD)-like symptoms in mice by suppressing inflammation and immune cell activation. This study highlights sclareol
Area of Science:
- Dermatology
- Immunology
- Natural Product Chemistry
Background:
- Atopic dermatitis (AD) is a prevalent chronic inflammatory skin condition affecting millions globally.
- Current AD treatments like corticosteroids and immunosuppressants carry significant adverse effects.
- There is a need for novel, safer therapeutic agents for managing AD.
Purpose of the Study:
- To investigate the therapeutic potential of sclareol, a natural diterpene, in a mouse model of atopic dermatitis.
- To elucidate the underlying mechanisms by which sclareol exerts its effects on AD-like skin lesions.
- To evaluate sclareol as a potential alternative treatment for atopic dermatitis.
Main Methods:
- An in vivo mouse model of atopic dermatitis (AD) was established using 2,4-dinitrochlorobenzene (DNCB) induction.
- Mice were treated with varying doses of sclareol (50 and 100 mg/kg) via intraperitoneal injection.
- Key assays included ELISA, histological analysis, flow cytometry, and Western blot to assess inflammatory markers and cellular responses.
Main Results:
- Sclareol treatment significantly reduced AD-like symptoms, including serum IgE levels and skin hyperplasia.
- Sclareol administration decreased the infiltration of mast cells and levels of pro-inflammatory cytokines (IL-6, IL-1b, TNF-a, IL-4, IFN-g, IL-17A).
- Sclareol suppressed T cell activation and key inflammatory signaling pathways, including NF-kB translocation and MAP kinase phosphorylation.
Conclusions:
- Sclareol demonstrates potent anti-inflammatory and immunomodulatory effects against DNCB-induced atopic dermatitis.
- The findings suggest that sclareol inhibits AD pathogenesis by downregulating inflammatory mediators and signaling pathways.
- Sclareol shows promise as a potential therapeutic agent for clinical management of atopic dermatitis, warranting further investigation.
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