Sargassum horneri is a well-known edible brown alga that is widely abundant in the sea near China, Korea, and Japan and has a wide range of bioactive compounds. Fucosterol (FST), which is a renowned secondary metabolite in brown algae, was extracted from S. horneri to 70% ethanol, isolated via high-performance liquid chromatography (HPLC), followed by the immiscible liquid-liquid separation, and its structure was confirmed by NMR spectroscopy. The present study was undertaken to investigate the effects of FST against oxidative stress, inflammation, and its mechanism of action in tumor necrosis factor (TNF)-α/ interferon (IFN)-γ-stimulated human dermal fibroblast (HDF). FST was biocompatible with HDF cells up to the 120 μM dosage. TNF-α/IFN-γ stimulation significantly decreased HDF viability by notably increasing reactive oxygen species (ROS) production. FST dose-dependently decreased the intracellular ROS production in HDFs. Western blot analysis confirmed a significant increment of nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) involvement in FST-treated HDF cells. In addition, the downregulation of inflammatory mediators, molecules related to connective tissue degradation, and tissue inhibitors of metalloproteinases were identified. TNF-α/IFN-γ stimulation in HDF cells increased the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) mediators, and its phosphorylation was reduced with the treatment of FST in a dose-dependent manner. Results obtained from western blot analysis of the NF-κB nuclear translocation were supported by immunocytochemistry results. Collectively, the outcomes suggested that FST significantly upregulates the Nrf2/HO-1 signaling and regulates NF-κB/MAPK signaling pathways to minimize the inflammatory responses in TNF-α/IFN-γ-stimulated HDF cells.
Keywords: MAPK; NF-κB; Nrf2/HO-1; Sargassum horneri; fucosterol; human dermal fibroblasts.