Abstract
Atopic dermatitis (AD) is characterized by chronic highly pruritic and relapsing inflammatory skin lesions. Despite its growing prevalence, therapeutic treatments remain limited. Natural immune modulators from herbal extracts or derivatives may be useful for treating AD symptoms. This study examined the effect of 7,8,4′-trihydroxyisoflavone (7,8,4′-THIF), a metabolite of soy isoflavone daidzin, on AD-like symptoms. Repeated epicutaneous application of 2,4-dinitrochlorobenzene (DNCB) was performed on the ear and dorsal skin of NC/Nga mice to induce AD-like symptoms and skin lesions, and 7,8,4′-THIF (200 and 400 nmol) or tacrolimus (100 µg) was applied topically for 3 weeks to assess their anti-pruritic effects. We found that 7,8,4′-THIF alleviated DNCB-induced AD-like symptoms as quantified by skin lesion, dermatitis score, ear thickness, and scratching behavior. Histopathological analysis demonstrated that 7,8,4′-THIF decreased DNCB-induced eosinophil and mast cell infiltration into skin lesions. We also found that 7,8,4′-THIF significantly alleviated DNCB-induced loss of water through the epidermal layer. In addition to reducing the DNCB-induced increase in serum IgE, 7,8,4′-THIF also lowered skin lesion levels of the chemokine thymus and activation regulated chemokine; Th2 cytokines interleukin (IL)-4, IL-5, and IL-13; and Th1 cytokines IL-12 and interferon-γ. These results suggest that 7,8,4′-THIF might be a potential therapeutic candidate for the treatment of atopic dermatitis.
Highlights
Atopic dermatitis (AD) is a chronic inflammatory skin disease that is increasingly more common in infants and children [1,2]
The clinical symptoms of AD are characterized by elevated serum immunoglobulin E (IgE) levels and pruritic and relapsing eczematous skin lesions, which are distinguished by epidermal thickening; defective skin barriers; and infiltration of inflammatory cells, such as lymphocytes, macrophages, eosinophils, and mast cells [1,2,3,4,5]
Our results demonstrate that topical application of 7,8,49-THIF attenuated DNCB-induced AD-like symptoms in NC/Nga mice. 7,8,49-THIF treatment significantly alleviated DNCB-induced increases in skin lesion severity, dermatitis score, ear thickness, scratching behavior, and serum IgE levels
Summary
Atopic dermatitis (AD) is a chronic inflammatory skin disease that is increasingly more common in infants and children [1,2]. Histological examinations have revealed hyperplasia and dense accumulation of eosinophils and mast cells in skin lesions [14,17,20]. Along with these skin changes, NC/Nga mice exhibit elevated levels of total serum IgE [14,15]. We investigated whether topical application of 7,8,49-THIF suppressed the development of AD-like symptoms and skin lesions in DNCB-treated NC/Nga mice by quantifying dermatitis score, ear thickness, scratching behavior, and serum IgE production. The effects of 7,8,49-THIF on eosinophil and mast cell infiltration and transepidermal water loss (TEWL) were investigated in skin lesions. The effects of 7,8,49-THIF were compared with those of tacrolimus, an immunosuppressant commonly used to treat AD (eczema)
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