Design and Preliminary In Vivo Evaluation of J2H-1802, a Hybrid Compound Derived from 5-ASA and MMF, in a DSS-Induced Colitis Mouse Model

초록

Background/Objectives: Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by epithelial injury and excessive inflammatory responses. J2H-1802 is a newly synthesized hybrid molecule designed to combine the pharmacological properties of mycophenolate mofetil and 5-aminosalicylic acid. This study evaluated the protective and anti-inflammatory effects of J2H-1802 in a dextran sulfate sodium (DSS)-induced colitis mouse model and investigated its underlying mechanisms. Methods: Experimental colitis was induced in mice by administration of 2.5% (w/v) DSS for 7 days, followed by oral treatment with J2H-1802. Body weight, stool consistency, fecal bleeding, and disease activity index were assessed. Colon length and spleen weight were measured to evaluate macroscopic damage. Levels of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and myeloperoxidase in colon tissues were quantified, and the expression of phosphorylated nuclear factor-kappa B and cyclooxygenase-2 was analyzed by Western blotting. Results: J2H-1802 alleviated DSS-induced body weight loss, diarrhea, and fecal bleeding, resulting in reduced disease activity index scores. It also prevented colon shortening and attenuated splenomegaly. In addition, J2H-1802 significantly suppressed the elevated levels of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and myeloperoxidase in colon tissues. Western blot analysis further showed that J2H-1802 inhibited the DSS-induced upregulation of phosphorylated nuclear factor-kappa B and cyclooxygenase-2. Conclusions: J2H-1802 protected against DSS-induced colitis by reducing inflammatory responses and inhibiting the nuclear factor-kappa B/cyclooxygenase-2 signaling pathway. These findings suggest that J2H-1802 functions as a hybrid anti-inflammatory scaffold with in vivo pharmacological activity and may warrant further optimization and investigation in IBD models.

키워드