A Traditional Herbal Formula Attenuates Chronic Pruritus by Inhibiting IgE—FcεRI Signaling and Sensory Neuron Activation 2333596

Introduction Chronic pruritus is a debilitating symptom accompanying various inflammatory and dermatologic diseases, yet currently available antipruritic therapies show limited efficacy and frequent adverse effects. Growing interest has therefore focused on mechanism-based and safer alternatives, including traditional herbal medicines. Cheonwangbosim-dan (CWB), a classical Korean herbal formula, was identified as a potential antipruritic candidate, although its immunological and sensory neuronal mechanisms remain unclear. Methods We screened 26 traditional formulations using a biochip assay to evaluate inhibition of IgE—FcεRI binding. CWB’s effect on mast cell degranulation was measured via histamine release in MC/9 cells. In vivo efficacy was assessed using an imiquimod-induced zebrafish inflammation model (locomotor activity and qRT-PCR for il-1β, il-6, il-33, and trpa1) and a histamine-induced mouse scratching model. Furthermore, sensory neuronal activity was monitored via in vivo calcium imaging of dorsal root ganglion (DRG) neurons in GCaMP-transgenic mice following oral or topical CWB administration. Results CWB demonstrated the strongest inhibition of IgE—FcεRI binding among the screened candidates and significantly reduced mast cell histamine release. In zebrafish, CWB dose-dependently suppressed imiquimod-induced hyperlocomotion and downregulated key pro-inflammatory and pruritus-related genes. In murine models, both oral and topical CWB markedly attenuated histamine-induced scratching. Notably, in vivo imaging revealed that CWB significantly inhibited histamine-evoked DRG neuronal activation without inducing spontaneous activity. Conclusion CWB exhibits potent antipruritic activity through dual modulation of immune-mediated histamine signaling and sensory neuronal responsiveness. This combined mechanism distinguishes CWB from conventional antipruritic agents and supports its potential as a safe and effective complementary therapy for chronic pruritus. Funding Source Portions of this work was carried out within the Korea Institute of Oriental Medicine, (grant number KSN18384113).