Papaverine ameliorates psoriasis-like skin inflammation by regulating immune cell differentiation and RAGE-S100A7 axis in an imiquimod-induced murine model.

Abstract

Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting at least 2% of the global population. Papaverine, an alkaloid with known anti-inflammatory, anti-cancer, and RAGE-antagonistic properties, has not been previously evaluated for anti-psoriatic activity. This study investigated the protective effects and mechanisms of papaverine in an imiquimod (IMQ)-induced psoriasis-like model in BALB/c mice. Papaverine treatment significantly ameliorated clinical symptoms, as evidenced by reductions in psoriatic lesions, skin thickness, severity index scores, T- and B-cell infiltration, and cutaneous angiogenesis. It also downregulated IMQ-induced mRNA expression of keratinocyte differentiation markers Krt10 and Ivl. Flow cytometric analysis revealed a marked reduction in B220⁺CD138⁺ plasmablasts and B220⁻CD138⁺ plasma cells in both circulation and spleen. These effects were associated with modulation of key transcription factors involved in plasma cell differentiation, including Prdm1, Xbp1, and Bcl6. Notably, the population of CD3⁺CD4⁻CD8⁻ double-negative T cells was also decreased following papaverine administration. Inflammatory cytokine and chemokine mRNA levels in IMQ-exposed skin-namely Il1b, Il6, Ifng, Mcp1, Il22, S100a7, and Ager-were significantly suppressed. These findings suggest that papaverine ameliorates psoriasis-like symptoms through inhibition of proinflammatory cytokines and suppression of aberrant plasma cell differentiation. In conclusion, papaverine demonstrates therapeutic potential as a candidate for the treatment of psoriasis.