Licochalcone D Alleviates Psoriasiform Skin Inflammation by Inhibiting Kv1.3 Channels

<i>Objective: </i>To investigate the blocking effect of licochalcone D on the voltage-gated potassium channel Kv1.3 and its potential therapeutic efficacy in psoriasiform skin inflammation, thereby providing experimental evidence for its use as an immunomodulatory candidate drug. <i>Methods:</i> The inhibitory effects of licochalcone D on exogenous and endogenous Kv1.3 currents were recorded by whole-cell patch-clamp. Ca<sup>2+</sup> influx in Jurkat T cells was monitored with Fura-2 AM imaging. A ConA-induced T-cell activation model was established to quantify IL-2 secretion. An imiquimod-induced psoriasis-like mouse model was then established for in-vivo pharmacodynamic evaluation of licochalcone D. <i>Results:</i> Licochalcone D concentration-dependently inhibited Kv1.3 currents, with IC<sub>50</sub> values of 28.77 ± 3.40 nM in HEK293T cells and 497.72 ± 87.30 nM in Jurkat T cells. Ca<sup>2+</sup> imaging revealed that it suppressed Ca<sup>2+</sup> influx in T cells. Animal studies demonstrated that licochalcone D markedly improved psoriasiform lesions (erythema, scaling, thickening), reduced PASI scores and itching, alleviated epidermal hyperplasia and inflammatory infiltration, and down-regulated IL-6, IL-17, and IL-23 expression. <i>Conclusion: </i>Licochalcone D exerts immunomodulatory effects by blocking Kv1.3 channels, thereby alleviating psoriasiform skin inflammatory responses. This provides an experimental foundation and theoretical support for its potential as a targeted immunotherapy drug.