What question did this study set out to answer?

The study aims to evaluate the therapeutic effects of polydeoxyribonucleotide (PDRN) in a murine model of ulcerative colitis (UC).

May 31, 2026Open Access

Polydeoxyribonucleotide Mitigates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice Through the PKA/CREB/NF-κB Signaling Pathway

Key Points

The study aims to evaluate the therapeutic effects of polydeoxyribonucleotide (PDRN) in a murine model of ulcerative colitis (UC).
UC was induced in mice using 2% DSS in drinking water for 7 days.
Mice received intraperitoneal injections of PDRN (8 mg/kg) for 7 days following DSS administration.
The selective antagonist DMPX (8 mg/kg) was co-administered with PDRN to investigate A2AR involvement.
DSS administration increased disease activity index (DAI) and histological scores, indicating colonic damage.
PDRN treatment reduced histological damage, improved body weight, and decreased DAI scores after DSS exposure.
PDRN inhibited NF-κB activation and enhanced VEGF expression, contributing to tissue repair mechanisms.

Abstract

Background/Objectives: Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by abdominal pain, diarrhea, and bleeding. Polydeoxyribonucleotide (PDRN), an adenosine A2A receptor (A2AR) agonist, exhibits anti-inflammatory properties. In the present study, we evaluated the therapeutic effects of PDRN in a dextran sodium sulfate (DSS)-induced murine model of UC. Methods: UC was induced by administering 2% DSS in drinking water for 7 days. One day after DSS administration, mice received intraperitoneal injections of PDRN (8 mg/kg) for 7 days. To investigate the involvement of A2AR, the selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX, 8 mg/kg) was co-administered with PDRN. Results: DSS administration induced colonic tissue damage and increased disease activity index (DAI) and histological scores. DSS also elevated pro-inflammatory cytokines while reducing anti-inflammatory cytokine levels. PDRN treatment reduced histological damage, restored body weight, colon weight, and colon length, and decreased DAI scores. Furthermore, PDRN treatment inhibited nuclear factor kappa B (NF-κB) activation through suppression of NF-κB inhibitor-α phosphorylation and was associated with activation of the cAMP/PKA/CREB signaling pathway. PDRN treatment attenuated inflammation and was associated with increased expression of vascular endothelial growth factor (VEGF) in colonic tissues. Given the context-dependent role of VEGF in inflammatory bowel disease, this increase is interpreted as contributing to mucosal repair rather than exacerbating inflammation. Co-administration of DMPX abolished these effects, suggesting the involvement of A2AR-dependent signaling pathways. Conclusions: PDRN attenuated colonic inflammation and improved disease outcomes in DSS-induced UC, potentially through modulation of the PKA/CREB/NF-κB signaling pathway and VEGF-mediated tissue repair mechanisms.

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