Myricetin Attenuates IMQ-Induced Psoriatic Inflammation Through Multi-Target Modulation: Evidence from Network Pharmacology and Experimental Validation

<b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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 <i>Mmp9</i>, <i>Ptgs2</i>, and <i>Tnf</i> expression. <b>Conclusions</b>: 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.