An Algal Metabolite-Based PPAR-γ Agonist Displayed Anti-Inflammatory Effect via Inhibition of the NF-κB Pathway.

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 gamma (PPAR-gamma) ligand 15-deoxy-(12,14)-prostaglandin J(2) (15d-PGJ(2)), exerted significant PPAR-gamma transcriptional activity. Because PPAR-gamma 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-gamma 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-alpha (TNF-alpha), possibly by the inhibition of the nuclear factor-kappa B (NF-kappa B) pathway. In macrophages, (+)-(R,E)-6a1 suppressed LPS-induced phosphorylation of NF-kappa B, inhibitor of NF-kappa B alpha (I kappa B alpha), and I kappa B kinase (IKK). These results indicated that PPAR-gamma agonist, (+)-(R,E)-6a1, exerts anti-inflammatory activity via inhibition of the NF-kappa B pathway.