Abstract
Ulcerative colitis (UC) is a relapsing inflammatory disease with a unique aetiology. The treatment of UC is challenging, and the current clinical therapeutics for colitis have limited efficacy. Thus, finding new and effective treatment options remains urgent. Baricitinib, an inhibitor of Janus kinase (JAK), has been clinically used to treat rheumatoid arthritis (RA). However, its potential effects on UC have not been fully elucidated. In this study, we aimed to explore the effects of baricitinib on UC and its underlying mechanism. Dextran sulphate sodium (DSS)-induced murine model of chronic colitis was used to investigate the intervention efficacy following oral administration of baricitinib. The levels of key cytokines, such as IL-6, IFN-γ and IL-17A, were determined. Moreover, western blotting for IκBα, p-IκBα, JAK2, p-JAK2, STAT3 and p-STAT3 protein expression was performed to investigate the associated signalling pathways. Our findings demonstrated that baricitinib can significantly relieve DSS-induced UC in mice. After baricitinib intervention, IL-6, IFN-γ and IL-17A levels were decreased both in vitro and in vivo. Moreover, the elevated expression levels of p-IκBα, p-JAK2, and p-STAT3 were significantly reduced after treatment. Collectively, these results suggest that baricitinib is a potential therapeutic agent for alleviation of DSS-induced colitis. This study provides a method for subsequent investigations on potential curative drugs development of the for colitis.
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Funding
This study was supported by the National Key R&D Program of Hubei Province (Grant No. 2022BCE040), the Biomedical Research Foundation, Hubei University of Medicine (Grant No. PI201804), and the Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine) (Grant No. WDCM2023020).
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All authors contributed to the study conception and design. QW, YL and JL performed the experiments, collected the data; DA, BD and XX analyzed the data; LJ and YG designed the study, wrote and revised the manuscript. All authors commented on previous versions of the manuscript, read and approved the final manuscript.
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All animal studies were conducted according to protocols approved by the Hubei University of Medicine Animal Care and Use Committee (Approval No: 2022068), complying with the rules of Regulations for the Administration of Affairs Concerning Experimental Animals (approved by the State Council of China).
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Wu, Q., Liu, Y., Liang, J. et al. Baricitinib relieves DSS-induced ulcerative colitis in mice by suppressing the NF-κB and JAK2/STAT3 signalling pathways. Inflammopharmacol 32, 849–861 (2024). https://doi.org/10.1007/s10787-023-01396-6
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DOI: https://doi.org/10.1007/s10787-023-01396-6