Bioactive dicaffeoylquinic acid-enriched callus extract of Weigela subsessilis inhibits TNF-α/IFN-γ-induced keratinocyte inflammation via MAPK and NF-κB pathways

초록

Inflammatory skin diseases (ISDs) involve chronic inflammation and excessive cytokine production, compromising skin function. Weigela subsessilis exhibits antioxidant and anti-inflammatory properties, yet its callus-derived bioactive potential remains unexplored. This study evaluates WS callus extract (WSCE) in TNF-alpha and IFN-gamma (T+I)-induced keratinocytes, identifying key metabolites and underlying molecular mechanisms for potential ISD treatment. WSCE (6.25-25 mu g/mL) substantially suppressed T+I-induced production of pro-inflammatory mediators (MCP-1, RANTES, MDC, CTACK, IL-6, and IL-8) and inhibited MAPK and NF-kappa B signaling pathways, but not the Akt pathway, underscoring its regulatory potential in inflammatory conditions. UHPLC-MS/MS and HPLC-DAD analyses identified chlorogenic acid (CGA; 30.1 mg/g) and three dicaffeoylquinic acids (DCQAs; 3,5-DCQA, 6.1 mg/g; 4,5-DCQA, 4.5 mg/g; 3,4-DCQA, 0.6 mg/g) as the primary bioactive compounds in WSCE. Functional evaluations showed that 3,5-DCQA and 4,5-DCQA considerably reduced MCP-1 levels (by 11.9%-32.7%), whereas CGA and 3,4-DCQA effectively diminished IL-8 levels (by 44.2%-55.6%). This study highlights WSCE as a potential anti-dermatitis agent, suppressing pro-inflammatory mediators (MCP-1, RANTES, MDC, CTACK, IL-6, IL-8) in T+I-stimulated keratinocytes via MAPK and NF-kappa B regulation. These findings underscore the therapeutic potential of callus-derived extracts and position WSCE as a promising candidate for ISD management.

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