P70 | Trichosanthin Targets WNT/Nf-Kb Pathways to Attenuate Psoriatic Inflammation and Keratinocyte Hyperproliferation

Psoriasis is a chronic immune-mediated inflammatory disorder characterized by accelerated keratinocyte proliferation and immune dysfunction1. Trichosanthin (TCS) demonstrates potent induction of apoptosis and regulates T-cell activities2. This was the first study to investigate the therapeutic effects of TCS topical application in the treatment of psoriasis. After a series of in vitro and in vivo experiments, we found that TCS significantly alleviated psoriatic lesions in mice, reducing PASI scores comparable to those achieved with tacrolimus. TCS also decreased the protein expression levels of Ki-67, KRT14, and IL-17, as well as reduced T cell infiltration in psoriatic skin tissue, and inhibited the expression of Ki-67, β-catenin, Wnt5a, STAT3, KRT14, and KRT17 in HaCat cells. Furthermore, TCS suppressed the protein levels of TRAF6, IKKα/β, and NF-κB, along with its phosphorylated form, and downregulated the mRNA expression of inflammatory cytokines including IL-17, IL-12, TNF-α, and IFN-γ. In summary, TCS effectively suppresses epithelial hyperproliferation, keratinization, and skin inflammation by modulating Wnt and NF- κB signaling pathways, underscoring its potential as a novel therapeutic agent for psoriasis.