Lindera obtusiloba extract attenuates cytokine-mediated epidermal inflammation in keratinocytes and an MC903-induced AD-like mouse model.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by dysregulated keratinocyte responses and excessive epidermal cytokine production. Although Lindera obtusiloba exhibits anti-inflammatory properties, the effects of its solvent-partitioned fractions on keratinocyte-driven cutaneous inflammation remain unclear. This study evaluated the anti-inflammatory activity of the methylene chloride fraction of L. obtusiloba using complementary in vitro and in vivo models. HaCaT keratinocytes were stimulated with IFN-γ/TNF-α or polyinosinic-polycytidylic acid, and IL-8 and thymic stromal lymphopoietin (TSLP) production was assessed following LM treatment, with cytotoxicity evaluated in parallel. Cutaneous inflammatory responses were examined in an MC903-induced AD mouse model. Cytokine expression and immune-cell profiles were analyzed using RT-qPCR and flow cytometry, and epithelial-monocytic inflammatory communication was assessed using a HaCaT-THP-1 co-culture system. LM significantly suppressed IL-8 and TSLP production in stimulated keratinocytes without cytotoxicity. In vivo, LM attenuated AD-like skin lesions, epidermal hyperplasia, immunoglobulin E levels, and inflammatory cytokine gene expression. Conservatively gated exploratory flow cytometric analysis of cervical lymph nodes suggested LM-associated changes in selected CD4+ T cell transcription factor-associated profiles, although these data were interpreted cautiously because FMO controls were not included. In the co-culture model, LM reduced inflammatory gene expression in THP-1 cells. Collectively, these findings indicate that LM suppresses keratinocyte-derived inflammatory mediator production and ameliorates MC903-induced AD-like epidermal inflammation, supporting its potential as a lignan-enriched anti-inflammatory fraction for AD-associated cutaneous inflammation.