Background/Objectives: Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by keratinocyte hyperproliferation and systemic inflammatory responses, which are primarily driven by the interleukin (IL)-23/Th17 axis. Although current therapies effectively suppress inflammation, their long-term use is often limited by adverse systemic effects, underscoring the need for safe immunomodulatory agents. This study investigated the anti-psoriatic efficacy of J2H-1802, a novel hybrid compound combining mycophenolate mofetil (MMF) and 5-aminosalicylic acid (5-ASA), in an imiquimod (IMQ)-induced psoriasis-like mouse model. Methods: J2H-1802 was orally administered at doses of 125 and 250 mg/kg during IMQ treatment, and its effects were evaluated by conducting clinical assessments, histological analyses, and inflammatory cytokine measurements in the serum and skin tissues. Results: J2H-1802 treatment reduced Psoriasis Area and Severity Index (PASI) scores, skin and ear thickness, and splenomegaly in a dose-dependent manner. Histological examination revealed IMQ-induced epidermal hyperplasia attenuation and dermal collagen organization improvement. In addition, J2H-1802 significantly reduced serum tumor necrosis factor-α (TNF-α) levels and suppressed pro-inflammatory cytokine expression, including IL-1β, IL-6, IL-17, and TNF-α, in psoriatic skin. Conclusions: J2H-1802 alleviates both local and systemic inflammatory features of psoriasis, suggesting its potential as a therapeutic candidate for targeting IL-23/Th17-mediated inflammatory pathways.

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-α, interleukin-1β, interleukin-6, and myeloperoxidase in colon tissues were quantified, and the expression of phosphorylated nuclear factor-κB 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-α, interleukin-1β, interleukin-6, and myeloperoxidase in colon tissues. Western blot analysis further showed that J2H-1802 inhibited the DSS-induced upregulation of phosphorylated nuclear factor-κB and cyclooxygenase-2. Conclusions: J2H-1802 protected against DSS-induced colitis by reducing inflammatory responses and inhibiting the nuclear factor-κB/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.