Oxymatrine ameliorates <i>Malassezia</i> overgrowth-induced psoriasis <i>in vivo</i> and <i>in vitro</i> by inhibiting the biofilm formation and inflammation

The basidiomycetous yeast genus Malassezia is involved in the exacerbation of psoriatic lesions. Oxymatrine (OMT), a quinoline alkaloid derived from Sophora flavescens, exhibits diverse pharmacological properties, including anti-inflammatory, anticancer, and antiviral effects. However, whether OMT exerts therapeutic effects against Malassezia-associated psoriasis remains unclear. This work aimed to study the antifungal and antibiofilm effect of OMT on several Malassezia species and the therapeutic benefits of OMT on Malassezia-associated psoriasis in vivo and in vitro. Treatment with 0.64 mg/mL OMT showed decreasing levels of biofilm formation of Malassezia species. Histomorphology and functional analyses demonstrated that OMT treatment effectively alleviated Malassezia-induced psoriatic lesions and repaired skin barrier integrity. Furthermore, the results demonstrate that OMT significantly reduced the levels of malonaldehyde, interleukin (IL)-6, IL-17, IL-23, and tumour necrosis factor (TNF)-α while promoting the activation of superoxide dismutase, catalase, and glutathione. OMT also reversed Malassezia-associated apoptosis and decreased the expression of the STAT3/Nf-κB/p-Nf-κB signalling pathway. Additionally, OMT reduces the nuclear expression of AhR/Nrf2 in Malassezia-stimulated HaCaT cells. In summary, this study demonstrated that OMT inhibits Malassezia biofilm formation and ameliorates Malassezia-associated psoriasis by modulating oxidative stress, inflammation, and apoptosis via STAT3/Nf-κB and AhR/Nrf2 pathways.