Assessment of the Efficacy and Safety of Melittin in a Mouse Model of Imiquimod-Induced Psoriasis: A preliminary study

Objective: Psoriasis is a well-known chronic immune-mediated skin disease with involved inflammatory and hyperkeratotic processes affecting skin health. The limitations of anti-psoriatic medications and the recurrent nature of the disease highlighted the need for developing possible therapeutic or adjuvant therapy for psoriasis. Melittin (Mel), the chief component of honeybee venom, exhibits potent anti-inflammatory and antioxidant properties in different disease models. This preliminary study aimed to investigate the dose-response effects and safety of melittin in imiquimod (IMQ)-induced psoriasis-like dermatitis in mice. Methods: This study was conducted to determine the safe and effective doses of Mel to be used in the main study. Psoriasis model was induced in BALB/c mice by daily topical application of 5% IMQ cream on the shaved mice's dorsal skin for seven consecutive days. Mice were randomly divided into six groups (n=6): control, IMQ, and IMQ+Mel-treated mice with daily intraperitoneal injections of melittin at 10, 20, 40, or 80 mg/kg. The shaved skin was observed daily to calculate Psoriasis Area and Severity Index (PASI), via scoring erythema, scaling, and thickening on a scale of 0-4. Systemic involvement was evaluated by calculating the spleen-to-body weight ratio at the end of the experiment. Animals’ general health, mortality rate, behavioral changes, signs of toxicity, and body weight were monitored daily as safety parameters. Results: topical application of IMQ resulted in well-developed psoriasis-like lesions, indicated by the significantly elevated PASI score and increased spleen index compared to the control group. Treatment with Mel exhibited a dose-dependent anti-psoriatic activity, as the doses of 10 and 20 mg/kg failed to achieve a significant improvement in PASI or the spleen index compared to the IMQ-treated group. Meanwhile, treatment with Mel at 40 and 80 mg/kg significantly alleviated psoriatic lesions, reduced PASI scores, and decreased spleen index. No obvious signs of toxicity, such as mortality, weight loss, or behavioral changes, were observed at any dose during the 7-day study period. Conclusion: This preliminary study demonstrates that Mel exhibited an anti-psoriatic activity against IMQ-induced psoriasis in mice in a dose-dependent manner, with a minimum effective dose of 40 mg/kg. Under the experimental conditions, Mel showed a favorable safety profile at all tested doses. These promising preliminary findings support the need for further investigation into the underlying molecular mechanisms of Mel in psoriasis.