Dysifragilone A inhibits LPS-induced RAW264.7 macrophage activation by blocking the p38 MAPK signaling pathway

摘要

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, anti-inflammatory 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 E-2,(PGE(2)) and interleukin-6 (IL-6). The protein expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and the enzymatic activity of iNOS and COX-2 were also inhibited by dysifragilone A in a dose dependent manner. Further mechanistic investigations suggested that the anti-inflammatory activity of dysifragilone A results from the suppression of p38 mitogen-activated protein kinase (MAPK) activation in LPS-activated macrophages; however, this was not associated with inhibition of the extracellular signal-regulated kinase (ERK) or c-Jun N-terminal kinase (JNK) signaling pathways. Therefore, dysifragilone A and similar compounds may be anti-inflammatories that have potential to be used in the clinic.