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Strictosamide alleviates the inflammation in an acute ulcerative colitis (UC) model

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Abstract

The ulcerative colitis (UC) is a typical inflammatory bowel disease (IBD) causing great damages, while strictosamide (STR) is a natural alkaloid that possesses strong anti-inflammatory property in infection and inflammation-related diseases. Our study is aimed at evaluating the anti-inflammatory activity of STR in the course of UC. Briefly, male Balb/c mice were treated with 3.5% dextran sulfate sodium (DSS) for 6 consecutive days to establish an acute model of UC, and the administration of gradient concentrations of STR was subsequently performed. Accordingly, colonic pathological alterations including the reduced ratio of colon weight/length, decreased disease activity index (DAI), and attenuated H&E damage were found in UC mice after STR treatment. Based on the analyses of real-time PCR and western blot, downregulation of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) was also determined in the colonic tissue of UC mice after the treatment of STR. ELISA and immunohistochemical staining further suggest the relief of inflammation in UC mice with decreased expressions of MPO and iNOS after STR treatment. In addition, STR was also validated to significantly inhibit NF-κB signaling in UC mice by western blot and Electrophoretic Mobility Shift Assay (EMSA). Meanwhile, restricted inflammation was also determined in STR-treated IEC6 and HT-29 cells. The utilization of PDTC, an inhibitor of NF-κB, further demonstrated that STR ameliorated the inflammation by inhibiting the NF-κB signaling in vitro. In summary, our study suggests that STR could be a potential candidate for IBD therapy.

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Funding

This research was funded by the Top Talent Project for Youths of Hebei Province (No. 180443), the Doctoral Startup Foundation of Hebei Normal University of Science & Technology (No. 2018YB018 and No. 2019YB005), the Project of Department of Science and Technology, Hebei Province (No. C2019407111), the Talent Engineering Training Funds of Hebei Province (No. A201903012), and the High School Hundred Excellent Innovation Talent Program of Hebei Province (No. SLRC2019048).

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Author notes

  1. Qinghui Jia and Haihua Zhang contributed equally to this research.

Authors and Affiliations

  1. Hebei Key Laboratory of Specialty Animal Germplasm Resources Exploration and Innovation (Under Planning), College of Animal Science and Technology, Hebei Normal University of Science & Technology, Qinhuangdao, 066004, China

    Qinghui Jia, Haihua Zhang, Yongmei Su, Xin Liu, Qiumei Shi & Minshan Feng

  2. Shijiazhuang Zhongnongtongchuang (ZNTC) Biotechnology Co., Ltd., Shijiazhuang, 052463, China

    Jiangsong Bai

  3. College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130118, China

    Wuying Lang

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  1. Qinghui Jia
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  4. Xin Liu
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Contributions

QHJ, HHZ, and MSF designed the study. HHZ, YMS, and XL performed the research. QHJ and JSB analyzed the data. WYL and QMS contributed to the details of methods and materials. QHJ and HHZ wrote the paper. MSF revised and modified the manuscript to the final version. QHJ and HHZ contributed equally to this research.

Corresponding author

Correspondence to Minshan Feng.

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Ethical approval

All animal experiments were approved by the Animal Ethics Committee of Hebei Normal University of Science & Technology. All operations were conducted according to the Guide to the Care and Use of Experimental Animals.

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All authors declare that they have no conflict of interest.

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Key Points

1. Strictosamide alleviated the pathological alterations in DSS-induced acute UC mice.

2. Strictosamide relieved the inflammation in DSS-induced acute UC mice.

3. Strictosamide inhibited the inflammatory response in LPS-induced IEC6/HT-29 cells by restricting the NF-κB pathway.

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Jia, Q., Zhang, H., Su, Y. et al. Strictosamide alleviates the inflammation in an acute ulcerative colitis (UC) model. J Physiol Biochem 77, 283–294 (2021). https://doi.org/10.1007/s13105-021-00796-y

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