Role Of Curcumin Ramification FM 0815 In The Protection Of Septic Model

Background and ObjectiveSepsis is a common inflammation syndrome induced by infection.Severe sepsis and septic shock are life threatening complications of infections and a common cause death in intensive care units.Recent US and European surveys show that severe sepsis account for 2-11%of all admissions tO hospitals or intensive care units.Among them,the hospital mortality rate from severe sepsis and septic shock remains over 30-60%.Unfortunately,there are currently no effective drugs to sepsis in clinical use.Curcumin is the primary curcuminoid being studied in a host of areas including antioxidant potential,Alzheimer's disease,inflammation,chemoprevention and chemotherapy.Pre-clinical studies in a variety of cancer cell lines have consistently shown that curcumin possesses anti-cancer activity in vitro.FM0815 was curcumin ramification.Brians showed that FM0815 had effectively reduced the sized of human breast tumor grown in female athymic dude mice and showed little toxicity.In the present study,the effect of FM0815 was observed by estabishing septic model in vivo and in vitro.Methods①In vitro,the contents of TNF-αand IL-6 in supematants were tested by ELISA after 1.0μg/ml LPS exposure.②The protection of FM0815 on spetic mice model was observed.Meanwhile, the plasma TNF-αand IL-6 of mice with or without treatment of FM0815 were tested.③The protein Hsp 70,NF-κB,P-P38 were tested by western blotting. Results①In vitro,the treatment of RAW264.7 with FM0815 potently inhibited the release of TNF-αand IL-6 induced by LPS in a dose-dependent manner (P＜0.05 or P＜0.01).②The three-day mortality in FM0815 group was significantly lower than that in the model group(P＜0.01).The treatment FM0815 significantly reduced the peak plasma concentrations of TNF-αand IL-6 in Septic mice model (P＜0.05 or P＜0.01 ).③The treatment of FM0815 significantly reduced the contens of Protein NF-κB in the intronuclear which was situmulated by LPS.Protein P-P38 in the spetic model in vitro was also reduced by the treatment of FM0815. While protein Hsp 70 was inceased by the treatment of FM0815.ConclusionsThe septic mice model was established,and the FM0815 miaght have protection of septic mice model.It was probably related to:①FM0815 might reduce systemic inflammatory response by inhibiting the activation of inflammatory cells and the release of inflammation mediators such as TNF-αand IL-6.②FM0815 might block the NF-κB and MAPK of septic mice model,which could ease the ability of destroy of LPS.In addition,the admistration of FM0815 might trigger the heat shock response to protect the septic mice model.