Enzymatically-modified isoquercitrin alleviates skin inflammation, mast cell degranulation, and vascular hyperpermeability in a mouse model of plaque psoriasis

Abstract

Psoriasis is a prevalent, autoimmune skin disease that easily relapses and is difficult to cure. Given its increased global prevalence and the limitations of synthetic therapies, developing of natural product-originated agents with fewer side effects and high therapeutic efficacy is of serious concern. Therefore, this work aimed to evaluate the potential effect of enzymatically-modified isoquercitrin (EMIQ, 50 and 100 mg/kg body weight "b.wt", administered orally for 8 days), in comparison with methotrexate (MTX, a synthetic drug), against imiquimod (IMQ)-induced psoriatic lesions in female BALB/c mice. Furthermore, the protective effect of EMIQ against the skin associated-vascular permeability response was investigated by using IMQ-induced Evans blue extravasation mouse model. The results showed that EMIQ (particularly at the higher dose) attenuated significantly (P < 0.05-0.001) all complications shown in psoriatic mice like MTX. These effects included reduction in the psoriasis area and severity index, prevention of b.wt loss, and alleviation of histopathological alterations and oxidative stress. Importantly, EMIQ reduced the elevated expression of interleukin (IL)-23 and IL-17A (the key cytokines involved in psoriasis pathogenesis), inhibited phosphorylation of nuclear factor-κBp65, and down-regulated tumor necrosis factor-α, IL-1β, and cyclooxygenase-2 levels in mice skin tissues. Moreover, oral administration of EMIQ prevented significantly (P < 0.001) the vascular permeability associated with augmented Evans blue leakage and dermal accumulation of degranulated mast cells, suggesting a reduction in inflammation and edema. Taken together, our study demonstrated that EMIQ can alleviate psoriasis and may be considered as a promising strategy for psoriasis treatment via targeting IL-23/IL-17A axis and mast cell degranulation.