A combination of Olea europaea leaf extract and Spirodela polyrhiza extract alleviates atopic dermatitis by modulating immune balance and skin barrier function in a 1-chloro-2,4-dinitrobenzene-induced murine model

Background: Atopic dermatitis is a chronic inflammatory skin disease in humans. Although Olea europaea leaf extract (OLE) and Spirodela polyrhiza extract (SPE) have been used to protect against skin damage, the effects of their combined administration on atopic dermatitis have yet to studied. Purpose: In this study, we evaluated the potential therapeutic effects of an OLE and SPE combination on the progression of atopic dermatitis and the possible mechanisms underlying these effects in 1-chloro-2,4-dinitroben-zene (DNCB)-treated NC/Nga mice. Methods: Atopic dermatitis was induced by topical application of 0.2% w/v DNCB prepared in an olive oil: acetone solution (1:3), and thereafter OLE, SPE and OLE + SPE were administered orally for 5 weeks. We determined atopic dermatitis symptoms, serum IgE levels, and levels of cytokine- and gene expression in the dorsal skin and splenocytes, and performed histological and immune cell subtype analyses. The expression of skin barrier-related proteins (filaggrin, sirtuin 1, and claudin 1) was also evaluated. Results: The OLE + SPE combination significantly ameliorated atopic dermatitis symptoms, including dermatitis scores, and reduced epidermal thickness and infiltration of different inflammatory cells in mice with DNCBinduced atopic dermatitis. It also significantly reduced the number of CD4(+), CD8(+), and CD4(+)/CD69(+) T cells; immunoglobulin E-producing B cells (CD23(+)/B220(+)) in the axillary lymph nodes; CD3(+) T-cell eosinophils (chemokine-chemokine receptor 3(+)/CD11b(+)) in the skin; and CD3(+) T cells, immunoglobulin E-producing B cells (CD23(+)/B220(+)), and eosinophils in peripheral blood mononuclear cells. Additionally, the experimental combination lowered levels of serum immunoglobulin E and histamine, as well as Th2-mediated cytokines, and interleukin-4, -5, and -13, whereas it increased the levels of Th1-mediated cytokine interferon-gamma in splenocytes. Furthermore, the preparation significantly restored expression of the skin barrier-related proteins filaggrin, sirtuin 1, and claudin 1, and also reduced the expression of the inflammatory cytokine interleukin-6 and chemokine-chemokine receptor 3, as well as the pruritus-related cytokine interleukin-31 and interleukin-31 receptor, in atopic dermatitis skin lesions. Conclusion: Taken together, our findings indicate that administration of a combination of OLE and SPE can alleviate atopic dermatitis symptoms by regulating immune balance and skin barrier function and may be an effective therapeutic option for the treatment of atopic dermatitis.