Polyphyllins ameliorate imiquimod-induced psoriatic skin barrier disruption and lesions in mice by inhibiting inflammatory infiltration with accelerated recovery effects.

BACKGROUND: Psoriasis is a chronic inflammatory skin disorder that significantly compromises patients' quality of life. While dexamethasone (DEX) is effective as a first-line treatment, its adverse effects highlight the need for alternatives. Effective therapies for prolonging clinical remission and reducing relapse rates remain limited. Our previous study demonstrated that Polyphyllin H (PPH) and PPH-enriched Rhizoma Paridis extract (RPE) possess great anti-inflammatory efficacy in vitro, with polyphyllins also improving skin barrier integrity. However, their therapeutic efficacy and safety in chronic inflammatory conditions remain unexplored. METHODS: In this study, we established an imiquimod (IMQ)-induced psoriasis model in BALB/c mice, in which psoriatic lesions were first induced by IMQ application and subsequently monitored for their regression upon IMQ withdrawal and treated with RPE, Polyphyllin H (PPH), and DEX. Psoriasis Area Severity Index (PASI) scores, pathohistological analysis and inflammatory cytokines expression of psoriasis-like mice were measured in different groups. RESULTS: Over a 12-day observation period, RPE significantly ameliorated psoriasis-like lesions, facilitating lesion remission. Histopathological analysis revealed that RPE prevented epidermal thickening with reduced Ki67 expression. Furthermore, PPH, the main active component of RPE, significantly improved PASI scores and reduced epidermal thickening in psoriasis-like lesions. Mechanistically, both PPH and RPE suppressed macrophage infiltration and downregulated key inflammatory cytokines associated with psoriasis. CONCLUSION: In conclusion, our findings establish polyphyllins as promising anti-inflammatory agents that promote psoriasis lesion resolution while offering a safer alternative to corticosteroids. Our study underscores the therapeutic potential of polyphyllins for psoriasis management and warrants further investigation into their clinical applicability.