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Therapeutic effect of the sulforaphane derivative JY4 on ulcerative colitis through the NF-κB-p65 pathway

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Abstract

The efficacy of the sulforaphane derivative JY4 was evaluated in acute and chronic mouse models of ulcerative colitis induced by dextran sodium sulfate. Oral administration of JY4 led to significant improvements in symptoms, with recovery of body weight and colorectal length, together with reduced diarrhoea, bloody stools, ulceration of colonic tissue and infiltration of inflammatory cells. The oral bioavailability of JY4, determined by comparing oral dosing with injection into the tail vein, was 5.67%, which was comply with the idea in the intestinal function. Using a dual-luciferase reporter assay, immunofluorescence studies, western blot analysis and immunohistochemical staining, JY4 was shown to significant interfere with the NF-κB-p65 signaling pathway. By preventing the activation of NF-κB-p65, JY4 inhibited the overexpression of downstream inflammatory factors, thereby exerting an anti-inflammatory effect on the intestinal tract. This study thus provides a promising candidate drug, and a new concept for the treatment of ulcerative colitis.

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Data Availability

All data generated or analysed during this study are included in this published article.

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Funding

This work was supported by the Natural Science Foundation of Tianjin, China (No. 16JCQNJC13800 to CG.B.).

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Author notes

  1. Xiu-Juan Zhao, Yi-Ran Zhang and Wen-Fei Bai have been contributed equally to this work.

Authors and Affiliations

  1. High-Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, 300457, Tianjin, P. R. of China

    Xiu-Juan Zhao, Tong-Yan Sun, Yu-Fen Yang, Tong-Xin Wang & Cui-Gai Bai

  2. Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, 300020, Tianjin, P. R. of China

    Yi-Ran Zhang

  3. College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, 163316, Daqing, P. R. of China

    Wen-Fei Bai

  4. College of Pharmacy, Nankai University, 300350, Tianjin, P. R. of China

    Yu-Fen Yang & Tong-Xin Wang

  5. Tianjin Jena Pharmaceutical Technology Development Co., LTD, 300000, Tianjin, P. R. of China

    Xiu-Juan Zhao

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  1. Xiu-Juan Zhao
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  7. Cui-Gai Bai
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Contributions

CGB designed the study. XJZ, YRZ and WFB performed the experiments. CGB, XJZ, and WFB, TYS analyzed the data. CGB, XJZ, YRZ,WFB, TYS, YFY and TXW was involved in discussion of the experiments. CGB Provided financial support and prepared the original manuscript. All authors read and approved the final paper.

Corresponding author

Correspondence to Cui-Gai Bai.

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The authors declare no competing interests.

Ethical approval

All experiments using animals reported herein were approved by the Animal Care and Use Committee of Tianjin international Joint Academy of BioMedicine (Tjab 2017–0301).

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Zhao, XJ., Zhang, YR., Bai, WF. et al. Therapeutic effect of the sulforaphane derivative JY4 on ulcerative colitis through the NF-κB-p65 pathway. Inflammopharmacol 30, 1717–1728 (2022). https://doi.org/10.1007/s10787-022-01044-5

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  • DOI: https://doi.org/10.1007/s10787-022-01044-5

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