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

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Abstract

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, 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-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 anti-inflammatory and antioxidation mechanisms are related to inhibition of NF-κB p65 nuclear translocation and c-Jun phosphorylation and to activation of Nrf2. 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.

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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 anti-inflammatory drug

AP-1:

Activator protein 1

JNK:

c-Jun N-terminal kinase

HO-1:

Heme oxygenase-1

SOD:

Superoxide dismutase

CAT:

Catalase

GSH:

Glutathione

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Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 30771921) and the National Science and Technology Major Project of China (2012ZX1002007-001, 2017ZX10202203-008).

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  1. Fei Cheng and Yuhe Chen contributed equally to this work.

Authors and Affiliations

  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

    Fei Cheng, Yuhe Chen, Zhu Zhan, Yu Liu, Peng Hu, Hong Ren & Mingli Peng

  2. Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China

    Huadong Tang

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  1. Fei Cheng
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Mingli Peng and Fei Cheng are responsible for design of this study. Fei Cheng and Yuhe Chen performed the experiments. All authors participated in data analysis and interpretation.

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Cheng, F., Chen, Y., Zhan, Z. et al. Curc-mPEG454, a PEGylated Curcumin Derivative, Improves Anti-inflammatory and Antioxidant Activities: a Comparative Study. Inflammation 41, 579–594 (2018). https://doi.org/10.1007/s10753-017-0714-2

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