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Curcumin analog C66 alleviates inflammatory colitis by inhibiting the activation of NF-κB

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Abstract

Background

The pathogenesis of inflammatory bowel disease (IBD) remains unclear. C66, a derivative of curcumin, reportedly exerts anti-inflammatory, antifibrotic and anti-apoptotic effects by targeting the JNK pathway. However, the effect of C66 against IBD is not clear. In this study, we aimed to investigate the effect of C66 against IBD.

Methods

C57BL/6J mice were treated with 2.5% DSS for 7 days, and then administered water for 3 days to develop the IBD mouse model. A mouse intestinal epithelial cell line, MODE-K, stimulated by lipopolysaccharide (LPS) was used as the in vitro model. The therapeutic effects of C66 were evaluated and the pharmacological mechanisms were explored.

Results

Compared to the model group, C66 treatment significantly reduced colitis-associated damage, including a decrease in disease activity index (DAI), a higher body weight and longer colon. In addition, the infiltration of distal inflammatory cells, loss of crypt tissues, and destruction of epithelial cells were reduced in C66-treated group. In addition, C66 treatment reduced fibrotic areas and inflammatory responses in the colon tissues, leading to increased epithelial cell proliferation and decreased apoptosis in colon. Furthermore, C66 treatment decreased the levels of p-JNK and p-P65, indicating that C66 inhibits the activation of the JNK and NF-κB signaling pathways induced by DSS in colon tissues. Finally, in vitro data show that C66 inhibited LPS-induced inflammation and apoptosis in small intestinal epithelial cells. 

Conclusions

The curcumin analog C66 exhibits its anti-inflammatory effect by inhibiting the DSS-induced activation of JNK/NF-κB signaling pathways. C66 may be a potential candidate for the treatment of IBD.

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Abbreviations

Bax:

BCL2-Associated X protein

Bcl-2:

B-cell lymphoma-2

Col-1:

Type 1 collagen

i.p.:

Intraperitoneal

IBD:

Inflammatory bowel disease

IHC:

Immunohistochemistry

IL-12:

Interleukin 12

IL-17:

Interleukin 17

IL-1β:

Interleukin 1β

IL-22:

Interleukin 22

IL-23:

Interleukin 23

IL-6:

Interleukin 6

INF-γ:

γ Interferon

IκB-α:

Inhibitor of NF-κB-α

JNK:

C Jun N-terminal kinase

MAPK:

Mitogen-activated protein kinase

NF-κB:

Nuclear factor kappa-B

NLRP3:

NLR family pyrin domain containing 3

P38:

Mitogen-activated protein kinase

STAT3:

Signal transducer and activator of transcription 3

TGF-β:

Transforming growth factor-β

Th17:

T helper cell 17

Timp-1:

Tissue inhibitor of metalloproteinase-1

TNF-α:

Tumor necrosis factor-α

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Funding

This study was supported by Key Research Project of Wenzhou City (ZY2021021).

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Authors and Affiliations

  1. The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, Zhejiang, China

    Chenghong Hu, Fang Huang, Yi Wang & Lijiang Huang

  2. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China

    Chenghong Hu, Yue Chen, Lingxi Zhang, Min Liu, Jie Yang & Yi Wang

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  1. Chenghong Hu
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  2. Yue Chen
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Contributions

CH, YW and LH contributed to the literature search and study design. CH, YC, LZ, ML and JY carried out the experiments. CH, FH and YW contributed to data collection and analysis. CH, LH and YW participated in the drafting of the manuscript. CH and YW revised the manuscript. All authors contributed significantly and approved the submission of this manuscript.

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Correspondence to Yi Wang or Lijiang Huang.

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Hu, C., Chen, Y., Zhang, L. et al. Curcumin analog C66 alleviates inflammatory colitis by inhibiting the activation of NF-κB. Inflammopharmacol 30, 2167–2179 (2022). https://doi.org/10.1007/s10787-022-01085-w

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