Curc-mPEG454,a Pegylated Curcumin Derivative,improves Anti-inflammatory And Antioxidant Activities:A Comparative Study

Background:We previously demonstrated that a PEGylated curcumin(CurcmPEG454)significantly inhibited cyclooxygenase 2(COX-2)expression and improved the progression of liver fibrosis.The current study systematically evaluates its anti-inflammatory and antioxidant activities in vitro in a comparative study with curcumin,aspirin,NS-398 and vitamin C.Methods:RAW264.7 murine macrophages were pretreated with CurcmPEG454,curcumin,aspirin,NS-398 or vitamin C at the indicated concentration for 2 h;then,the cells were stimulated with 1 μg/ml lipopolysaccharide(LPS)for 24 h.The levels of pro-inflammatory cytokines and mediators,including IL-6,TNF-α,PGE2,NO,and GSH,and the activities of COX-2,SOD,and CAT,and the transcription factors involved in inflammation,such as NF-κB,c-Jun and Nrf2,were measured.Results:Curc-mPEG454 showed lower cytotoxicity(IC50 57.8μM)when compared with that of curcumin(IC50 32.6μM)and inhibited the release of the inflammatory cytokines IL-6,TNF-α,IL-1β and MCP-1 in a concentration-dependent manner.At 16μM,Curc-mPEG454 was most potent in the suppression of COX-2 expression at a transcriptional level rather than in the suppression of the catalytic activity of COX-2.Like curcumin,Curc-mPEG454 significantly reduced intracellular ROS production and enhanced the activities of SOD and CAT and the level of GSH to protect cells from LPS-induced oxidative injury.Further,its antiinflammatory and anti-oxidation mechanism related to inhibit NF-κB p65 nuclear translocation and c-Jun phosphorylation and to activate Nrf2.Conclusions:Taken together,these findings indicate that PEGylation of curcumin not only improves its biological properties but also interferes with multiple targets involved in the inflammatory response.Curc-mPEG454 is a powerful and beneficial anti-inflammatory and antioxidant agent that merits further investigation.