A novel compound DSC suppresses lipopolysaccharide-induced inflammatory responses by inhibition of Akt/NF-κB signalling in macrophages

A novel compound [4-(2-acetoxy-3-((R)-3-(benzylthio)-1-methoxy-l-oxopropan-2-ylamino)-3-oxopropyl)-1,2-phenylene diacetate (DSC)], derived from Danshensu, exerted cytoprotective effects by anti-oxidative and anti-apoptotic activities in vitro. Herein, we reported the protective effects of DSC on lipopolysaccharide (LPS)-induced inflammatory responses in murine RAW264.7 macrophages and the underlying mechanisms. We showed that DSC concentration-dependently attenuated nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression with less cytotoxicity. Signal transduction studies indicated that DSC significantly inhibited LPS-induced phosphorylation of Akt, but not c-Jun N-terminal kinase 112, p38, or extracellular signal-regulated kinase 1/2. Meanwhile, LPS-induced nuclear translocation of nuclear factor-kappa B (NF-kappa B) p65 was decreased by DSC. Furthermore, a phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 significantly suppressed LPS-induced NF-kappa B p65 nuclear translocation, iNOS expression, and NO production, which was also mimicked by pretreatment with DSC. These results suggested that DSC attenuated LPS-induced inflammatory response in macrophages, at least in part, through suppression of PI3K/Akt signaling and NF-kappa B activation. (C) 2013 Published by Elsevier B.V.