An algal metabolite-based PPAR- Agonist displayed anti-inflammatory e-ect via inhibition of the nf-b pathway

Abstract

In our previous study, a synthetic compound, (+)-(R,E)-6a1, that incorporated the key structures of anti-inflammatory algal metabolites and the endogenous peroxisome proliferator-activated receptor (PPAR-) ligand 15-deoxy-D12,14-prostaglandin J2 (15d-PGJ2), exerted significant PPAR- transcriptional activity. Because PPAR- expressed in macrophages has been postulated as a negative regulator of inflammation, this study was designed to investigate the anti-inflammatory effect of the PPAR- Agonist, (+)-(R,E)-6a1. Compound (+)-(R,E)-6a1 displayed in vitro anti-inflammatory activity in lipopolysaccharides (LPS)-stimulated murine RAW264.7 macrophages. Compound (+)-(R,E)-6a1 suppressed the expression of proinflammatory factors, such as nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-), possibly by the inhibition of the nuclear factor-B (NF-B) pathway. In macrophages, (+)-(R,E)-6a1 suppressed LPS-induced phosphorylation of NF-B, inhibitor of NF-B (IB), and IB kinase (IKK). These results indicated that PPAR- Agonist, (+)-(R,E)-6a1, exerts anti-inflammatory activity via inhibition of the NF-B pathway.