Paeoniflorin alleviates urushiol-induced pruritus in mice by inhibiting Erk/CCL2 pathway

Paeoniflorin (PAE), a bioactive monoterpene glycoside derived from the roots of Paeonia lactiflora (P. lactiflora), has been traditionally used in East Asian medicine for its anti-inflammatory and immunomodulatory properties. However, its potential therapeutic effects on plant allergen-induced dermatitis, particularly poison ivy-related allergic contact dermatitis (ACD), remain unexplored. This study aimed to investigate the immune mechanisms underlying urushiol-induced ACD, a prevalent environmental allergy caused by poison ivy, and to evaluate the efficacy of PAE in alleviating inflammatory and pruritic responses. A murine ACD model was established using urushiol and compared with oxazolone-induced dermatitis. PAE was administered intraperitoneally for 7 days. Skin lesion severity, epidermal thickness, and inflammatory markers were assessed. Behavioral tests evaluated pruritus intensity. Urushiol-induced ACD exhibited more severe dermatitis than oxazolone, with pronounced epidermal hyperplasia, elevated CCL2 levels, and increased macrophage recruitment. PAE treatment significantly alleviated scratching behavior and reduced epidermal thickness. PAE also ameliorates urushiol-induced ACD by inhibiting Erk/CCL2-mediated macrophage recruitment and TSLP production, highlighting its potential as a natural therapeutic agent for plant allergen-driven dermatitis. Overall, this study bridges traditional use of P. lactiflora with modern mechanistic validation, supporting ethnopharmacological applications in immune-related skin disorders.