Celecoxib or diallyl trisulfide topical emulgels, alone or in combination, reduce pruritus and inflammatory cascades in a BALB/c mouse model of imiquimod-induced psoriasis

Abstract

Psoriasis is a chronic, immune-mediated inflammatory skin disease for which no curative treatment currently exists, posing a significant challenge because of its deleterious effects on patients’ quality of life and its substantial economic burden on healthcare systems. Current first-line therapies, including corticosteroids and systemic immunosuppressants, are associated with considerable local and systemic side effects, underscoring the need for safer topical alternatives. Topical celecoxib (CXB), a selective cyclooxygenase-2 inhibitor, suppresses prostaglandin-mediated inflammation and pain, whereas diallyl trisulfide (DATS), a naturally derived, slow-releasing hydrogen sulfide donor, has been shown to restore the Th17/Treg balance in other inflammatory disease models. The present study aimed to evaluate the effects of topical application of CXB and DATS emulgels, administered individually and in combination, against imiquimod (IMQ)-induced psoriasis in female BALB/c mice, using clobetasol as a benchmark comparator, and to investigate the underlying mechanisms. Treatment with CXB, DATS, or their combination significantly relieved pruritus, as demonstrated by reduced scratch bouts, improved Psoriasis Area and Severity Index (PASI) scores, amelioration of histopathological alterations, and restoration of spleen mass. CXB and DATS exerted their antipsoriatic effects by suppressing inflammation, as evidenced by inhibition of the IL-23/IL-22/IL-19/IL-17 axis and reduction of IL-6, JAK2/STAT3 total proteins, along with decreased TNF-α and IFN-γ levels, reduced myeloperoxidase (MPO) content, and diminished serotonin (5-HT) levels. CD4 + and CD8 + T-cell infiltration, assessed by histoscore, was likewise reduced. Across all assessed endpoints, the combination therapy showed encouraging outcomes that warrant direct comparison with clobetasol in future trials. In conclusion, CXB and DATS demonstrated protective effects against IMQ-induced psoriasis by attenuating pruritus and suppressing key inflammatory and immune signaling cascades involving the IL-23/IL-22/IL-19/IL-17 axis and the IL-6/JAK2/STAT3 cascade. These findings support the use of a CXB-DATS emulgel as a promising topical strategy for the treatment of psoriasis.