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

Abstract

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 E2,(PGE2) 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.

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