Zerumbone attenuates the excessive proliferation of keratinocytes in psoriasis mice through regulating NLRP3/NF-κB...

Psoriasis is a common chronic disease, and existing treatment regimens often exhibit certain toxicities and side effects. Zerumbone (Zer) may possess therapeutic effect, and the objective of this study is to investigate the effect of Zer on psoriasis. A mouse model of psoriasis was established using imiquimod cream, and the role of Zer on the pathological alterations in psoriatic mouse skin was evaluated by psoriasis area and severity index (PASI) score; the effect of Zer on keratinocyte proliferation was evaluated via hematoxylin and eosin staining, Zen image analysis, and immunofluorescence; Immunohistochemistry and enzyme-linked immunoassay were used to evaluate the effect of Zer on tissue inflammatory responses, while malondialdehyde (MDA) and glutathione (GSH) levels were measured to elucidate the role of Zer in modulating oxidative stress; the signaling pathway regulated by Zer was evaluated by western blotting. The results demonstrated that Zer could alleviate the pathological manifestations of psoriasis, reduce PASI score, reduce skin pathological damage and epidermal hyperplasia, diminish the number of CD8⁺ T cells and cytokine expression levels, decrease the level of MDA and GSH and increase the expression of Nrf and HO-1. Zer was found to regulate the NLRP3/nuclear factor-kappa B (NF-κB) signaling pathway. In conclusion, Zer ameliorated the symptoms of psoriasis in mice, suppressed the keratinocyte hyperproliferation, and mitigates inflammation and oxidative stress in psoriatic skin tissue by regulating the NLRP3/NF-κB pathway.