Sodium R-lipoate protects against psoriatic skin inflammation via modulating IL-23/IL-17A axis, oxidative stress, and mast cell activation.

Psoriasis is a prevalent dermatological condition characterized by chronic inflammation, affecting an estimated 2-3% of the global population. Current therapies for psoriasis can relieve symptoms, but their serious adverse effects and financial burdens are significant. Hence, it is urgent to focus on natural product-originated agents to develop much safer, more effective, and low-cost treatments. Here, we determined and compared the efficacy of sodium R-lipoate (NaRLA, 50 and 100 mg/kg body weight/day), given orally for 8 consecutive days, in a BALB/c mouse model of imiquimod-induced psoriatic skin inflammation, in comparison with the synthetic drug methotrexate (MTX). Moreover, the vascular permeability (Evans blue) response was investigated. Our results revealed that NaRLA (especially at the high dose) exhibited better performance like MTX in alleviating (P < 0.05-0.001) the symptoms of psoriasis (erythema, scaling, and skin thickness), as well as the psoriasis area and severity index score, body weight loss, splenomegaly, the deteriorating histopathology, and oxidative stress. Most importantly, NaRLA decreased (P < 0.05-0.001) the elevated expression of interleukin (IL)-23 and IL-17A (key cytokines involved in psoriasis pathogenesis), markedly inhibited phosphorylation of nuclear factor-κBp65, and downregulated tumor necrosis factor-α, IL-1β, and cyclooxygenase-2 levels in mice skin tissues. Furthermore, NaRLA resulted in a significant improvement (P < 0.001) on both Evans blue extravasation and mast cell degranulation, suggesting a reduction in inflammation and edema. Thus, our observations imply that NaRLA may serve as an effective agent for alleviating psoriatic skin inflammation via targeting IL-23/IL-17A axis and mast cell degranulation.