Open Access

ARTICLE

Procaine hydrochloride improves DSS-induced colitis via inhibition of IL-6/STAT3 and FOXP3 methylation

An Xiong^1,2,#, Yi Tian^3,#, Xin Liang⁴, Shaoqun Liu^1,2, Chencheng Shi^1,2, Yiou Cao^1,2,*, Chang Su^1,2,*

1 Department of Surgery, Minhang Hospital, Fudan University, Shanghai, China
2 Key Laboratory of Whole-period Monitoring and Precise Intervention of Digestive Cancer (SMHC), Minhang Hospital and AHS, Fudan University, Shanghai, China
3 Department of Stomatology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
4 Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China

* Corresponding Authors: Yiou Cao. Email: ; Chang Su. Email:
# An Xiong and Yi Tian contributed to the work equally and should be regarded as co-first authors

European Cytokine Network 2026, 37(2), 137-149. https://doi.org/10.32604/ecn.2026.084018

Received 15 April 2026; Accepted 28 May 2026; Issue published 30 June 2026

Abstract

Backgrounds: Disruption of immune barrier function is considered a hallmark feature of inflammatory bowel disease. In the present study, the potential effects of the methyltransferase inhibitor procaine hydrochloride on intestinal barrier integrity, as well as T cell differentiation in the context of inflammatory bowel disease were explored. Methods: Using an experimental model of dextran sulfate sodium-induced ulcerative colitis, mice received daily treatment with either sulfasalazine (100 mg/kg) or procaine hydrochloride (45 mg/kg), or saline (10 μL/g) as a negative control, for 7 consecutive days. Subsequent analysis included disease activity index score, histopathology, expression levels of intestinal epithelial tight junctions and apoptotic protein, production of inflammatory cytokines, frequencies of lymphocyte populations in the spleen by flow cytometry and methylation levels of Forkhead box protein 3 (FOXP3). Results: Procaine alleviated dextran sulfate sodium-induced colitis, with a reduced disease activity index (p < 0.05) and histopathological score (p < 0.001). Procaine treatment resulted in a 1.96-fold increase in splenic FOXP3⁺ CD25⁺ Tregs (p < 0.001). Administration of procaine significantly enhanced tight junction expression (p < 0.01), decreased the expression of BAX and cleaved caspase-3 protein expression, while increasing that of the anti-apoptotic protein BCL-2. Procaine also significantly suppressed IL-6/signal transducer and activator of transcription factor 3 (STAT3) signaling pathway. In addition, procaine amplified FOXP3⁺ Tregs by inhibiting FOXP3 methylation. Conclusions: The protective potential of procaine hydrochloride against intestinal barrier injury in colitis may be attributed to increased abundance of Tregs and the augmentation of their anti-inflammatory properties. The potential mechanisms may involve modulation of IL-6/STAT3 signaling pathway and inhibition of FOXP3 methylation.

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