Rutin ameliorates imiquimod-induced psoriasis-like skin lesions by inhibiting oxidative stress injury and the inflammatory response in mice via the Keap1/Nrf2 signaling pathway.
Psoriasis is a chronic inflammatory skin disease with a high world-wide incidence. Rutin, a natural citrus flavonoid glycoside, has been shown to have anti-inflammatory and antioxidant properties. To investigate the protective effects of rutin in imiquimod (IMQ)-induced psoriasis model mice and its underlying molecular mechanism. IMQ was applied to mice to induce inflammatory skin that phenotypically mimics psoriasis. The Psoriasis Area Severity Index (PASI) score was used to evaluate the degree of erythema, scale and thickening of skin lesions. The inflammatory cytokines and oxidative stress factors were measured to evaluate the anti-inflammatory and antioxidant effects of rutin. Finally, experiments were performed using Nrf2-deficient mice to determine the underlying molecular mechanism of rutin in the treatment of psoriasis. Mice treated with rutin showed reduced erythema, scaling, and epidermal thickening compared to mice without treatment. In skin tissue, topical administration of rutin inhibited the IMQ-induced increases in reactive oxygen species, nitric oxide, and malondialdehyde, and significantly increased the IMQ-induced decreases in total antioxidant capacity, superoxide dismutase, and glutathione peroxidase. Additionally, the expression levels of the pro-inflammatory cytokines IL-6, IL-1β, IL-17A, and IL-23A were significantly increased in the IMQ-treated group compared to the control group, but were significantly reduced by rutin. Importantly, Nrf2-deficient mice exhibited aggravated psoriasis-like symptoms and reduced response to rutin treatment. Our data evidence that rutin ameliorated IMQ-induced psoriasis-like skin lesions by inhibiting oxidative stress injury and the inflammatory response via the Keap1/Nrf2 pathway, suggesting a potential therapeutic role for rutin in the psoriasis treatment.
