Anhydroicaritin-loaded mesenchymal stem cell exosomes ameliorate psoriasis via ACSL4-mediated ferroptosis in mice

Psoriasis is a chronic inflammatory skin condition that is associated with endocrine imbalances and immune system dysregulation. Anhydroicaritin (ANH), derived from Bushen Huayu Decoction, possesses a variety of bioactivities. However, the therapeutic potential of ANH and the underlying molecular mechanisms in psoriasis remain poorly understood. In this study, we evaluate the efficacy of ANH in an imiquimod (IMQ)-induced psoriasis female mouse model and investigated its effects on human keratinocytes along with the mechanistic pathways involved. Our data show that ANH spray significantly improves skin lesions by reducing abnormal proliferation, cytokine release, and infiltration of Th1/Th17 cells in both lipopolysaccharide (LPS)-stimulated HaCaT cells and IMQ-induced lesional model mice. Moreover, extracellular vesicle (EV)-ANH demonstrates enhanced therapeutic effects. Furthermore, RNA-seq indicates that the therapeutic effect of ANH is achieved through the inhibition of acyl-CoA ligase family member 4 (ACSL4)-dependent ferroptosis. These results suggest that ANH holds promise as a therapeutic agent for psoriasis treatment.