Ethnopharmacological investigation of Elaeocarpus sylvestris leaf extract in mitigating atopic dermatitis-like lesions via inflammatory signaling modulation

초록

Ethnopharmacological relevance Historically, Elaeocarpus sylvestris has served as a traditional medicinal agent for inflammatory disorders across East Asia. Recent studies have reported its antioxidant and anti-inflammatory activities, supporting its potential as a natural therapeutic resource for inflammatory skin diseases such as atopic dermatitis (AD). However, its pharmacological relevance to AD and the cellular signaling cascades remain insufficiently elucidated. Aim of the study This study aimed to pharmacologically validate the traditional use of E. sylvestris by investigating the anti-inflammatory and anti-atopic effects of its leaf ethanol extract (ESLE) and elucidating the associated molecular mechanisms. Materials and methods Inflammatory profiles of LPS-primed HaCaT cells were analyzed to evaluate the bioactivity of ESLE. We employed western blotting to dissect the intracellular signaling networks, focusing on the IRAK4-mediated MAPK, NF-κB, and JAK/STAT pathways. The study also extended to a DNCB-induced murine model of AD, facilitating a comprehensive assessment of efficacy of ESLE through histopathological examination and transepidermal water loss measurements. Results Geraniin was confirmed as a representative biomarker to verify ESLE's identity. ESLE significantly inhibited NO and PGE2 production by downregulating iNOS and COX-2, while reducing pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in keratinocytes. These effects were mediated by the suppression of IRAK4-dependent MAPK, NF-κB, and JAK/STAT signaling. Furthermore, ESLE improved skin barrier function and attenuated AD hallmarks, including mast cell infiltration, serum IgE elevation, and lymphoid organ hypertrophy. Conclusions ESLE attenuates inflammatory responses and improves AD-like symptoms, potentially through modulation of inflammation-related signaling pathways. These findings support the pharmacological relevance of E. sylvestris and its traditional use in inflammatory skin conditions.

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