Dysifragilone A inhibits LPS­induced RAW264.7 macrophage activation by blocking the p38 MAPK signaling pathway.

Dysifragilone A, a sesquiterpene aminoquinone based on a rearranged avarone skeleton, has been previously isolated and identified from the South China Sea sponge Dysidea fragilis. In the present study, anti­inflammatory activity and the underlying molecular mechanism of dysifragilone A were studied using the classical inflammation model of lipopolysaccharide (LPS)­activated RAW264.7 macrophage cells and an MTT assay, Griess method, ELISA and western blotting were used. The results revealed that dysifragilone A significantly reduced the release of inflammatory mediators and inflammatory cytokines in activated RAW264.7 cells, including nitric oxide (NO), prostaglandin E2,(PGE2) and interleukin­6 (IL­6). The protein expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase­2 (COX­2), and the enzymatic activity of iNOS and COX­2 were also inhibited by dysifragilone A in a dose dependent manner. Further mechanistic investigations suggested that the anti­inflammatory activity of dysifragilone A results from the suppression of p38 mitogen­activated protein kinase (MAPK) activation in LPS­activated macrophages; however, this was not associated with inhibition of the extracellular signal­regulated kinase (ERK) or c­Jun N­terminal kinase (JNK) signaling pathways. Therefore, dysifragilone A and similar compounds may be anti­inflammatories that have potential to be used in the clinic.