Ameliorative Effects of Escin on Inflammation via Glucocorticoid Receptor (GR) in Atopic Dermatitis (AD) Mouse Model
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Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by intense itching. Escin, derived from Aesculus hippocastanum, has several pharmacological functions, including anti-inflammatory and anti-viral effects, and exhibits glucocorticoid-like actions in inflammatory responses. However, its impact on AD has not been extensively studied. We investigated the antiinflammatory effects of escin on AD and elucidate its underlying mechanism of actions in the dermatophagoides farinae extract (DFE)-induced AD mouse model. The AD-induced group treated with escin showed a significant reduction in immunoglobulin E (IgE) levels, ear thickness, epidermal thickness, and mast cell infiltration compared to the AD group. Additionally, escin significantly reduced the dermatitis score and the sizes of the spleen and lymph nodes. Notably, escin inhibited the reduction of filaggrin expression induced by DFE, while suppressing the upregulation of thymic stromal lymphopoietin (TSLP), interleukin (IL)-4, IL-13, IL-1β, and tumor necrosis factor (TNF)-α. Escin also significantly suppressed DFE-induced NF-κB expression. Interestingly, pre-treatment with RU486, a glucocorticoid receptor (GR) antagonist, attenuated the therapeutic effects of escin. In line with these findings, escin modulated the IFN-γ/TNF-α-mediated changes in TSLP and filaggrin expression in HaCaT keratinocyte cells. Furthermore, escin inhibited the lipopolysaccharide (LPS)- induced overproduction of nitric oxide (NO), protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and mRNA expression of IL-6 and IL-1β in RAW 264.7 cells. These results indicate that escin may offer therapeutic potential in treating AD through the GR.
Abstract
Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by intense itching. Escin, derived from Aesculus hippocastanum, has several pharmacological functions, including anti-inflammatory and anti-viral effects, and exhibits glucocorticoid-like actions in inflammatory responses. However, its impact on AD has not been extensively studied. We investigated the antiinflammatory effects of escin on AD and elucidate its underlying mechanism of actions in the dermatophagoides farinae extract (DFE)-induced AD mouse model. The AD-induced group treated with escin showed a significant reduction in immunoglobulin E (IgE) levels, ear thickness, epidermal thickness, and mast cell infiltration compared to the AD group. Additionally, escin significantly reduced the dermatitis score and the sizes of the spleen and lymph nodes. Notably, escin inhibited the reduction of filaggrin expression induced by DFE, while suppressing the upregulation of thymic stromal lymphopoietin (TSLP), interleukin (IL)-4, IL-13, IL-1β, and tumor necrosis factor (TNF)-α. Escin also significantly suppressed DFE-induced NF-κB expression. Interestingly, pre-treatment with RU486, a glucocorticoid receptor (GR) antagonist, attenuated the therapeutic effects of escin. In line with these findings, escin modulated the IFN-γ/TNF-α-mediated changes in TSLP and filaggrin expression in HaCaT keratinocyte cells. Furthermore, escin inhibited the lipopolysaccharide (LPS)- induced overproduction of nitric oxide (NO), protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and mRNA expression of IL-6 and IL-1β in RAW 264.7 cells. These results indicate that escin may offer therapeutic potential in treating AD through the GR.