Melittin attenuates imiquimod-induced psoriatic dermatitis in mice: a role for autophagy activation via PI3K/Akt/mTOR...

Despite multiple therapeutic strategies, a significant proportion of psoriatic patients fail to achieve complete/sustained disease clearance, highlighting the need for effective adjuvant or alternative therapy. Melittin, the main component in bee venom, exhibits valuable anti-inflammatory and immunomodulatory properties in various diseases; meanwhile, its effect on psoriasis has not been explored yet. Our study aims to investigate the anti-psoriatic effect of melittin with possible involvement of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) and the autophagy pathways. Mice were divided into 5 groups: Control group, Imiquimod (IMQ) group, and groups (3-5) received daily intraperitoneal injections of methotrexate (MTX, 1 mg/kg), melittin (40 mg/kg), or melittin (80 mg/kg), respectively. All groups except the control received topical IMQ for seven days. Melittin 80 demonstrated superior efficacy, significantly reducing the clinical Psoriasis Area and Severity Index score by 60% and epidermal thickening by 58.55%. Mel 80 decreased malondialdehyde by 62.32%, increased glutathione by 1.44-fold, and reduced nuclear factor-kappa B p65, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, IL-23, and IL-17 levels by 72.10%, 83.70%, 61.54%, and 58.09%, 64.55%, and 55.19%, indicating suppression of the pathogenic IL-23/IL-17 axis. Furthermore, Melittin 80 inhibited PI3K/Akt pathway, decreasing p-Akt and PI3K by 50.88% and 57.30%, leading to downregulation of phosphorylated mammalian target of rapamycin (p-mTOR) by 58.53% and a 3.01-fold increase in Beclin-1, indicating restored autophagy. Epidermal proliferation was reduced, with a 58.80% reduction in Epidermal Growth Factor Receptor and 46.51% reduction in Ki67 expression. These results suggest that melittin may represent a promising antioxidant and anti-inflammatory agent for psoriasis, acting through PI3K/Akt/mTOR pathway inhibition and autophagy restoration.