Curc-mPEG454, a PEGylated Curcumin Derivative, Improves Anti-inflammatory and Antioxidant Activities: a Comparative Stud

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ORIGINAL ARTICLE

Curc-mPEG454, a PEGylated Curcumin Derivative, Improves Anti-inflammatory and Antioxidant Activities: a Comparative Study Fei Cheng,1 Yuhe Chen,1 Zhu Zhan,1 Yu Liu,1 Peng Hu,1 Hong Ren,1 Huadong Tang,2 and Mingli Peng 1,3

We previously demonstrated that a PEGylated curcumin (Curc-mPEG454) 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. RAW264.7 murine macrophages were pretreated with Curc-mPEG454, 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, Abstract—

Fei Cheng and Yuhe Chen contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10753-017-0714-2) contains supplementary material, which is available to authorized users. 1

Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China 2 Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China 3 To whom correspondence should be addressed at Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China. E-mail: [email protected] ABBREVIATIONS PGE2, Prostaglandin E2; COX-2, Prostaglandin-endoperoxide synthase 2; LPS, Lipopolysaccharide; ROS, Reactive oxygen species; NF-κB, Nuclear factor kappa-light-chain-enhancer of activated B cells; Nrf2, Nuclear factor (erythroid-derived 2)-like 2; IL-6, Interleukin 6; TNF-α, Tumor necrosis factor alpha; IL-1β, Interleukin 1 beta; MCP-1, Monocyte chemoattractant protein 1; iNOS, Nitric oxide synthase; NO, Nitric oxide; PEG, Polyethylene glycol; NSAID, Non-steroidal antiinflammatory drug; AP-1, Activator protein 1; JNK, c-Jun N-terminal kinase; HO-1, Heme oxygenase-1; SOD, Superoxide dismutase; CAT, Catalase; GSH, Glutathione

0360-3997/17/0000-0001/0 # 2017 Springer Science+Business Media, LLC, part of Springer Nature

Cheng, Chen, Zhan, Liu, Hu, Ren, Tang, and Peng and Nrf2, were measured. Curc-mPEG454 showed lower cytotoxicity (IC50 57.8 μM) when compared with that of curcumin (IC50 32.6 μM) and inhibited the release of the inflammatory cytokines IL-6, TNF-α, IL-1β, and MCP-1 in a concentration-dependent manner. At 16 μM, Curc-mPEG454 was most potent in the suppression of COX-