Abstract
Background: Psoriasis is a chronic inflammatory skin disease driven by keratinocyte hyperproliferation and immune dysregulation. Despite the availability of biologics and immunosuppressants, recurrence and adverse effects remain major limitations. Myricetin (Myr), a natural flavonoid with well-documented anti-inflammatory and immunomodulatory properties, has shown promise in inflammatory disorders; however, its efficacy and mechanisms in psoriasis have not been fully elucidated. Methods: The therapeutic effects of topical Myr (0.5-2%) were evaluated in an imiquimod (IMQ)-induced psoriatic mouse model. Network pharmacology and molecular docking were employed to predict potential targets, followed by validation using histological analysis, cytokine profiling, qPCR, and Western blotting. Results: Network analysis identified 52 overlapping targets between Myr and psoriasis, including TNF, PTGS2, MMP9, and EGFR, with enrichment in TNF, IL-17, and PI3K/AKT signaling pathways. Myr treatment significantly alleviated IMQ-induced erythema, scaling, and epidermal thickening, improved skin-barrier function, and reduced the expression of IL-6, IL-17A, and TNF-α. Molecular docking showed strong binding affinities of Myr with TNF, PTGS2, MMP9, and EGFR. Western blotting confirmed that Myr suppressed EGFR and AKT phosphorylation and downregulated Mmp9, Ptgs2, and Tnf expression. Conclusions: Myr exerts multi-target anti-psoriatic effects by inhibiting the EGFR/AKT axis and inflammatory mediators, highlighting its potential as a safe and effective natural therapeutic agent for psoriasis.