Treatment With Schistosoma Japonicum Peptide SJMHE1 and SJMHE1-Loaded Hydrogel for the Mitigation of Psoriasis.

Abstract

Purpose: Harnessing helminth-induced immunomodulation offers a novel therapeutic avenue for autoimmune and inflammatory diseases; however, research on helminths against psoriasis remains limited. This study evaluates the effects of the peptide SJMHE1 from Schistosoma japonicum (S. japonicum) on the inflammatory response in imiquimod (IMQ)-induced psoriasis mice and LPS-stimulated keratinocytes, as well as the efficacy of SJMHE1-loaded hydrogel on psoriasis in mice.

Methods: SJMHE1 was administered to mice with IMQ-induced psoriasis via topical administration or subcutaneous injection, and effects were evaluated by detecting the skin inflammation of mice. LPS-stimulated HaCaT cells were used to assess the regulatory effects of SJMHE1 in vitro. Additionally, the effects of Poloxamer 407 (P407)-loaded SJMHE1 were evaluated in mice with IMQ-induced psoriasis through topical application.

Results: Topical administration and subcutaneous injection of SJMHE1 alleviated psoriasis-like skin lesions, improved PASI scores, reduced epidermal thickness and dermal inflammatory cell infiltration, and decreased expression of Ki67, a marker of keratinocyte proliferation or differentiation. SJMHE1 modulated pro-inflammatory and anti-inflammatory cytokine expression in LPS-treated HaCaT cells, down-regulating NF-κB and STAT3 activation. Both SJMHE1-loaded hydrogel and SJMHE1 treatment alleviated IMQ-induced psoriasis-like skin lesions, improved PASI scores, reduced the number of Ki67-positive epidermal cells, decreased the spleen index and T-cell infiltration, increased the proportion of regulatory T cells (Tregs), and decreased the percentage of Th17 cells, alongside reducing inflammatory cytokine expression and NF-κB and STAT3 activation in skin lesions. Notably, weight changes in the SJMHE1-loaded gel group were less than those in the betamethasone-positive control group on days 6, 7, and 8 post-IMQ administration.

Conclusion: SJMHE1-loaded hydrogel and SJMHE1 treatment inhibited NF-κB and STAT3 activation in skin lesions, improved Th17/Treg balance, and reduced inflammatory cytokine expression in psoriasis mice, thereby ameliorating psoriatic lesion symptoms. Furthermore, SJMHE1-loaded hydrogel exhibited fewer side effects compared to betamethasone, positioning it as a promising strategy against psoriasis.