Limonin alleviates imiquimod-induced psoriasis-like skin inflammation in mice model by downregulating inflammatory responses

Psoriasis is a chronic inflammatory condition affecting 1–2% of the global population. Phytomedicine, which uses plant-based compounds, is emerging as a promising approach to managing such inflammatory diseases. Limonin, a phytochemical found in citrus fruits and known for its bitter taste, possesses significant pharmacological properties. In this study, we evaluated the anti-psoriatic effects of limonin using a psoriasis-induced mice model. BALB/c mice were treated with imiquimod to induce psoriasis and then administered limonin at doses of 20 and 40 mg/kg/day for 6 days. Tacrolimus ointment served as a positive control. We assessed the hematological profile to determine limonin’s impact on leukocytes in the psoriasis model. Additionally, histomorphometric analysis of ear and skin tissues was conducted to evaluate the therapeutic effects of limonin. We further investigated the antioxidant properties of limonin by measuring levels of antioxidants and oxidative stress markers. The anti-inflammatory effects were evaluated by quantifying inflammatory cytokines and signaling proteins. In vitro, the cytotoxicity and anti-inflammatory potential of limonin were assessed using murine macrophage RAW264.7 cells. Our findings showed that limonin significantly reduced leukocyte counts, decreased inflammatory cell infiltration, and improved skin histoarchitecture in psoriasis-induced mice. Limonin also effectively scavenged free radicals and reduced levels of inflammatory cytokines and proteins without causing cytotoxicity in RAW264.7 cells. Overall, our in vivo and in vitro results confirm that limonin is a potent anti-inflammatory agent that effectively ameliorates imiquimod-induced psoriasis.