Phlorofucofuroeckol-A refined by edible brown algae Ecklonia cava indicates anti-inflammatory effects on TNF-α/IFN-γ-stimulated HaCaT keratinocytes and 12-O-tetradecanoylphorbol 13-acetate-induced ear edema in BALB/c mice

The present study investigated the anti-inflammatory potential of phlorofucofuroeckol-A (PFF-A) from Ecklonia cava in TNF-alpha/IFN-gamma-stimulated HaCaT keratinocytes and an acute ear edema mice model. Upon investigation, PFF-A had no cytotoxicity up to 62.5 mu g/mL and indicated a dose-dependent-cytoprotective effect with a reduction of intracellular ROS in TNF-alpha/IFN-gamma-stimulated HaCaT keratinocytes. PFF-A downregulated the mRNA expression of inflammatory cytokines (IL-25, IL-33, TSLP, IL-1(i, IL-6, IL-8, IL-13, IFN-gamma, and TNF-alpha) and che-mokines (Eotaxin, MDC, RANTES, and TARC) in TNF-alpha/IFN-gamma-stimulated HaCaT keratinocytes. Furthermore, PFF-A inhibited the activation of the NFicB/MAPK signaling whereas activated the Nrf2/HO-1 signaling. As an extended evaluation, PFF-A treatment significantly decreased the ear thickness and the expression of inflam-matory mediators including iNOS and COX-2 in the TPA-induced ear edema mice model. This study suggests the anti-inflammatory potential of PFF-A in the skin and the potential of E. cava consisting of PFF-A to develop functional foods that have effects on abnormal immune responses.