Artemisinin analogues are effective in the treatment of psoriasis by targeting RORγt

Abstract

Psoriasis is a chronic inflammatory skin autoimmune disease. Th17 cells, when pathologically activated, significantly contribute to the progression of psoriasis. The symptoms of this skin condition could be notably alleviated by targeting and suppressing the activity of these cells. Retinoic acid receptor-associated orphan nuclear hormone receptor γ-t (RORγt), a critical transcription factor in Th17 cells, emerges as a promising therapeutic target for autoimmune conditions which are mediated by the dysregulation of these cells. In this study, we designed and synthesised a series of artemisinin analogues based on the chemical structure of artemisinin, and screened 3 compounds, QHS-1, QHS-2, and QHS-3, with better inhibition efficiency of RORγt activity. We found that each of the three artemisinin analogues were demonstrated efficacy in curbing IMQ-induced skin inflammation and the abnormal proliferation of keratinocytes within the BALB/c mouse model of psoriasis. Our findings indicate that the three artemisinin analogues not only effectively mitigated skin inflammation and the abnormal proliferation of keratinocytes in the IMQ-induced psoriasis model of BALB/c mice but also curtailed the infiltration of immune cells and the production of pro-inflammatory cytokines in the dermis. Furthermore, these compounds modulated the cytokine expression profiles within Th17 cells. They exerted a suppressive effect on the activity of Th17 cells by targeting RORγt, thereby dampening the inflammatory response in the dorsal skin of the mice. This inhibition led to a reduction in the pathological proliferation of keratinocytes. In conclusion, our research underscores the promising therapeutic potential of artemisinin analogues in the treatment of psoriasis, offering a slate of candidate compounds which could pave the way for novel drug development in this field.