Tangeretin alleviates psoriasis through inhibition of the IL-23/IL-23R signaling pathway

Psoriasis is a chronic immune-mediated skin disease characterized by strong genetic susceptibility and autoimmune components. Identifying lead compounds from natural products for psoriasis has been proposed as a promising therapeutic strategy. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese medicine material rich in polymethoxy flavonoids with anti-inflammatory, antioxidant, and immunomodulatory activities. Whereas, the bioactive constituents of CRP responsible for anti-psoriatic effects and its underlying mechanism have yet to be elucidated. In this study, we employed network pharmacology analysis to pinpoint tangeretin (Tan) as the major anti-psoriatic component of CRP, and further systematically evaluated its anti-psoriatic effects and investigated its underlying mechanisms. Tan significantly attenuated IMQ-induced psoriasiform skin lesions in mice, as evidenced by the remarkably decrease in erythema, scaling, skin thickness, inflammatory cell infiltration, and several inflammatory factors. Further mechanism revealed that Tan inhibited the binding of IL-23 to the IL-23 receptor, and suppressed downstream JAK2/STAT3 and MAPK activation, thereby reducing inflammation and attenuating psoriasis progression. Overall, these findings provide strong evidence for Tan represents to be developed into a therapeutic candidate for psoriasis management. Our study also provides a scientific rationale for the therapeutic application of CRP against psoriasis.