Anti-inflammatory effects of chromene derivatives isolated from marine algae via suppressing NF-κB and MAPK pathways

Abstract

In this study, the anti-inflammatory effect of chromene derivatives, which was isolated from Sargassum siliquastrum were evaluated by examining their inhibitory effects on pro-inflammatory mediators in LPS-stimulated murine macrophage RAW 264.7 cells. The chromene derivatives were isolated from activity-guided fraction using inhibition of NO production and identified as sargachromanol D, E, G and I on the basis of a comparison of NMR spectroscopic data. Among them, sargachromanol G (SG) was selected for further experiments due to its profound inhibitory effect in all inflammatory mediators. SG dose-dependently inhibited the production of inflammatory markers (NO, iNOS, PGE2, and COX-2) and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) induced by LPS treatment. To further elucidate the mechanism of this inhibitory effect of SG, we studied LPS induced NF-κB activation and MAPKs phosphorylation. SG inhibited the phosphorylation IκB-α and NF-κB (p65 and p50) and MAPK (ERK1/2, JNK, and p38) in a dose dependent manner. These results suggest that the anti-inflammatory activity of SG results from its modulation of pro-inflammatory cytokines and mediators via the suppression of NF-κB activation and MAPK phosphorylation.64.7 cells. The chromene derivatives were isolated from activity-guided fraction using inhibition of NO production and identified as sargachromanol D, E, G and I on the basis of a comparison of NMR spectroscopic data. Among them, sargachromanol G (SG) was selected for further experiments due to its profound inhibitory effect in all inflammatory mediators. SG dose-dependently inhibited the production of inflammatory markers (NO, iNOS, PGE2, and COX-2) and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) induced by LPS treatment. To further elucidate the mechanism of this inhibitory effect of SG, we studied LPS induced NF-κB activation and MAPKs phosphorylation. SG inhibited the phosphorylation IκB-α and NF-κB (p65 and p50) and MAPK (ERK1/2, JNK, and p38) in a dose dependent manner. These results suggest that the anti-inflammatory activity of SG results from its modulation of pro-inflammatory cytokines and mediators via the suppression of NF-κB activation and MAPK phosphorylation.