Licoisoflavone B alleviates psoriasis via SCD1-targeted lipid metabolism reprogramming and suppression of Th17/IL-17-mediated inflammation.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disorder driven by dysregulated immune responses, Th17 cells activation, and keratinocytes hyperproliferation. Despite advances in therapies, high costs and adverse effects limit their utility. Licoisoflavone B (Lico B), bioactive flavonoid derived from licorice, exhibits anti-inflammatory and metabolic modulating properties, yet its mechanisms in psoriasis remain unexplored. METHODS: We employed integrative bioinformatics, including target prediction, differential expression analysis, and weighted gene co-expression network analysis to identify psoriasis-associated hub genes linked to Lico B. Functional enrichment was analyzed via GO and KEGG pathway. Molecular docking evaluated Lico B's binding affinity to candidate target. The effects of Lico B on Stearoyl-CoA Desaturase 1 (SCD1) expression, lipid metabolism, IL-17-induced keratinocyte proliferation, and Th17 differentiation. RESULTS: Bioinformatics revealed Lico B's targets were enriched in lipid metabolism and cell cycle pathways. SCD1 emerged as a key target, supported by strong binding affinity in docking studies. Experimentally, Lico B attenuated IL-17-induced SCD1 upregulation and lipid droplet accumulation in keratinocytes. It suppressed hyperproliferation markers (KRT17/Ki67) in cells and imiquimod-induced psoriatic mice. Furthermore, Lico B reduced Th17 differentiation and IL-17 production in murine models, demonstrating dual antiproliferative and immunomodulatory effects. CONCLUSION: Lico B alleviates psoriasis by targeting SCD1 to modulate lipid metabolism, inhibit keratinocyte hyperproliferation, and dampen Th17/IL-17-driven inflammation. This multimodal mechanism positions Lico B as a novel therapeutic candidate for psoriasis and related inflammatory-metabolic dermatoses.