Anti-Psoriatic Effects of J2H-1802, a Mycophenolate Mofetil and 5-Aminosalicylic Acid Hybrid, in an Imiquimod-Induced Psoriasis-like Mouse Model

<b>Background/Objectives</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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. <b>Conclusions</b>: 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.