Cynarin ameliorates dextran sulfate sodium-induced acute colitis in mice through the STAT3/NF-κB pathway

Abstract

Objective

Cynarin is a derivative of hydroxycinnamic acid presented in various medicinal plants, such as Cynara scolymus L. and Onopordum illyricum L. To date, the antioxidant and antihypertensive activities of cynarin have been reported. However, whether cynarin has a therapeutic impact on ulcerative colitis (UC) is unclear. Therefore, the aim of this study was to explore the potential effect of cynarin on dextran sulfate sodium (DSS)-induced acute colitis in vivo and on lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced RAW264.7 and J774A.1 cellular inflammation model in vitro.

Methods and Results

In this study, we investigated that cynarin alleviated clinical symptoms in animal models, including disease activity index (DAI) and histological damage. Furthermore, cynarin can attenuate colon inflammation through decreasing the proportion of neutrophils in peripheral blood, reducing the infiltration of neutrophils, and macrophages in colon tissue, inhibiting the release of pro-inflammatory cytokines and suppressing the expression of STAT3 and p65. In cellular inflammation models, cynarin inhibited the expression of M1 macrophage markers, such as TNF-α, IL-1β, and iNOS. Besides, cynarin suppressed the expression of STAT3 and p65 as well as the phosphorylation of STAT3, p65. Cynarin inhibited the polarization of RAW264.7 and J774A.1 cells toward M1 and alleviated LPS/IFN-γ-induced cellular inflammation.

Conclusion

Considering these results, we conclude that cynarin mitigates experimental UC partially through inhibiting the STAT3/NF-кB signaling pathways and macrophage polarization toward M1. Accordingly, cynarin might be a potential and effective therapy for UC.

Keywords:

• Cynarin
• colitis
• inflammatory response
• STAT3/NF-κB

Author contribution statement

Data collection: Shumin Chen, Shaoshuai Tang; design of the study: Chunbin Zhang, Yuanyue Li; statistical analysis: Shumin Chen; analysis and interpretation of the data: Shumin Chen, Shaoshuai Tang; drafting the manuscript: Shaoshuai Tang; critical revision of the manuscript: Chunbin Zhang and Yuanyue Li.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.

Data availability statement

Data will be made available on request.

Additional information

Funding

This work was supported by grants from the General Project of Fujian Natural Science Foundation (No. 2022J01531), the Open Project Program of Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education (No. LPHGRD2022-005), the Science and Technology Innovation Team Cultivation Program of Zhangzhou Health Vocational College (No. kjcx-07), and the Major Technology Program of Industry‑University‑Research Cooperation in Fujian Province (No. 2021Y4013).