Abstract
Introduction
Ulcerative colitis (UC) is an inflammatory intestine disease characterized by dysfunction of the intestinal mucosal barrier, ferroptosis, and apoptosis. Previous researches suggest that celecoxib, a nonsteroidal anti-inflammatory drug, holds promise in alleviating inflammation in UC. Therefore, this study aims to investigate the effects and mechanisms of celecoxib in UC.
Methods
To identify ferroptosis-related drugs and genes associated with UC, we utilized the Gene Expression Omnibus (GEO), FerrDb databases, and DGIdb database. Subsequently, we established a 2.5% DSS (Dextran sulfate sodium)-induced colitis model in mice and treated them with 10 mg/kg of celecoxib to validate the bioinformatics results. We evaluated histological pathologies, inflammatory response, intestinal barrier function, ferroptosis markers, and apoptosis regulators.
Results
Celecoxib treatment significantly ameliorated DSS-induced UC in mice, as evidenced by the body weight change curve, colon length change curve, disease activity index (DAI) score, and histological index score. Celecoxib treatment reduced the level of pro-inflammatory factors and promoted the expressions of intestinal tight junction proteins such as Claudin-1 and Occludin, thereby restoring the integrity of the intestinal mucosal barrier. Furthermore, celecoxib treatment reversed the ferroptosis characteristics in DSS-induced mice by increasing glutathione (GSH), decreasing malondialdehyde (MDA), and increasing the expression of GPX-4 and xCT. Additionally, apoptosis was induced in mice with UC, as evidenced by increased Caspase3, BAD, P53, BAX, Caspase9 and Aifm1 production, and decreased expression of BCL-XL and BCL2. Celecoxib treatment significantly reversed the apoptotic changes in DSS-induced mice.
Conclusion
Our findings suggest that celecoxib effectively treats DSS-induced UC in mice by inhibiting ferroptosis and apoptosis.
HIGHLIGHTS
Celecoxib enhancing intestinal barrier function
Celecoxib alleviates ferroptosis in DSS-induces ulcerative colitis
Celecoxib effectively alleviates apoptosis signaling pathway
Acknowledgements
We thank Wang Huizhen, Yu Kexun, Zhang Chaoyang, Wang Mingliang and Wu Youliang at the first affiliated hospital of Anhui medical university. We would like to thank the grants from the Scientific Research Project Plan for Anhui Universities (2022AH051192).
Authors contributions
Li Yaxian and Li Yongxiang designed the study; Li Yaxian, Ma Mengdi, Wang Xiaodong, Li Jing, Fang Ziqing and Li Jianhui performed the experiments; Li Yaxian, Wang Xiaodong and Xu Xin analyzed the data; Li Yaxian and Wang Xiaodong wrote the manuscript; Lu Yida and Xu Xin edited the manuscript. All authors approved the final manuscript.
Ethical approval
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Anhui medical university B (Date: 3/1/2018/No: 20180345).
Consent to participate
Written informed consent was obtained from individual or guardian participants.
Consent to publish
All authors read and approved the final manuscript for publication.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data availability statement
The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Data are not publicly available due to privacy or ethical restrictions. Additional supporting data may be provided as supplementary information files in the online version of this article or hosted in a publicly accessible repository, where details of the repository and accession numbers are provided within the article.