Sakuranetin modulates IL-17A-related inflammation and enhances skin barrier function in an imiquimod-induced psoriasis model

Sakuranetin, a methoxylated flavanone with known anti-inflammatory and antioxidant properties, has yet to be explored for its therapeutic potential in psoriasis treatment. This study evaluates its efficacy in an imiquimod-induced psoriasis-like murine model, focusing on both immune modulation and skin barrier restoration. Topical administration of sakuranetin significantly attenuated psoriatic inflammation, with high-dose treatment achieving comparable efficacy to desoximetasone. RNA sequencing and qPCR validation revealed that sakuranetin modulates keratinization, cornified envelope formation, and kallikrein-related peptidase activity, suggesting its role in epidermal homeostasis. Notably, sakuranetin selectively downregulated IL-17A while maintaining IL-17F expression, supporting a targeted immunomodulatory effect. Additionally, sakuranetin upregulated KRT1, KRT16, KLK7, Sprr2f, and Wfdc18 while downregulating Sprr2k and Sprr3, indicating a refined regulation of skin barrier proteins. The observed upregulation of Tslp suggests a potential role in epidermal repair mechanisms. These findings highlight sakuranetin as a novel, plant-derived therapeutic candidate with dual anti-inflammatory and skin barrier-enhancing properties, providing a potential corticosteroid-sparing approach for long-term psoriasis management.