TRPV1 Blocker, Peptide HCRG21 from Sea Anemone Heteractis magnifica, Exhibits Effectiveness in Psoriasis and Dermatitis in In Vivo Models

Psoriasis and allergic contact dermatitis (ACD) are the most common chronic inflammatory diseases, which are accompanied by epithelial alterations and a T cell-mediated immunopathology. In this study, we investigated the anti-ACD and anti-psoriasis effects of sea anemone <i>Heteractis magnifica</i> peptide HCRG21, a blocker of the TRPV1 channel, in 2,4-dinitrofluorobenzene (DNFB)- and imiquimod (IMQ)-induced mouse models, respectively. We found that topical application of 0.005-0.1% HCRG21 gels normalized hematological and immunological blood parameters in mice, significantly reduced the severity of ACD- and psoriasiform-like skin lesions, and increased the rate of tissue repair. The use of 0.005 and 0.05% HCRG21 gels decreased the production of IL-23-A and macrophage-derived chemokine (MDC) proteins in blood plasma, reduced the expression of <i>Tnf</i>, <i>Il1β</i>, <i>Il6</i>, <i>Il23a</i>, and <i>Il17a</i> genes, but increased the levels of the <i>Il10</i> gene in scabs and/or blood of IMQ-treated mice. On the other hand, topical application of 0.05 and 0.1% HCRG21 reduced the expression of <i>Il6</i> and <i>Il23a</i> in the DNFB-treated mice's blood and it had no significant effects on TNF-α and IL-1β production. Thus, HCRG21 has the potential to be a treatment for psoriasis and dermatitis due to its potent anti-inflammatory properties. This effect is achieved by reducing pro-inflammatory cytokines associated with TRPV1 and normalizing immune cell levels in the bloodstream. This, in turn, leads to a decrease in clinical symptoms and an improvement in skin healing.