Antioxidant And Anti-inflammatory Activities Of Curcumin Derivative FM0818

Object Sepsis is systemic inflammatory response (SIR) cause the infection in a systemic inflammatory response. Sepsis has become a worldwide problem for the complex pathogenesis, the major damage to body tissues and the difficulty to treat.Curcumin, the main active ingredient in turmeric root, is a known antioxidant, anti-inflammatory, and can reduce inflammatory mediators. A series of curcumin derivatives have recently been synthesized in our laboratory and FM0818 is one of them. In this study,we established the mouse macrophage inflammation model in vitro and mouse sepsis in vivo and investigated the effect and mechanism of FM0818 on inflammatory mediators production by mouse macrophages and its protective effect and mechanism against sepsis in mice.Methods1 Antioxidant activity of FM0818 was determined by the free radical DPPH, oxygen and Hydroxyl scavenging method.2 In vitro, the contents of TNF-αand IL-6 in supernatants were tested by ELISA after stimulated by LPS (1.0μg/ml). And the concentration of NO was determined by Nitrate Reductase-Assay (NRA).3 The protection of FM0818 on septic mice model was observed. Meanwhile, content of TNF-α, IL-6, NO, MDA and SOD of mice with or without treatment of FM0818 were determined.4 The protein NF-κB were tested by western blotting. ROS released by cells were test by DCFH-DA.Results1 FM0818 has strong scavenging effect on DPPH, O2·- ,·OH, acting in a concentration- dependent manner;2 In vitro, the treatment of RAW264.7 cell with FM0818 potently inhibited the release of TNF-αand IL-6 induced by LPS in a dosage-dependent manner(P<0.05 or P <0.01);3 The three-day mortality in FM0818 group was significantly lower than that in the model group(P <0.01).The treatment FM0818 significantly reduced the peak plasma concentrations of TNF-αand IL-6 in Septic mice model (P <0.05 or P <0.01)4 The treatment of FM0818 significantly reduced the contents of Protein NF-κB and ROS in the intra-nuclear which was stimulated by LPS.ConclusionThe septic mice model was established, and the FM0818-mediated protection of in septic mice model was probably related to:1. FM0818 might reduce systemic inflammatory response by inhibiting the activation of inflammatory cells and the release of inflammation mediators such as TNF-α, IL-6 and NO.2. FM0818 might block the NF-κB of septic mice model, which could ease the ability of destroy of LPS. In addition, the administration of FM0818 might reduce the release of ROS to protect the septic mice model.