Oral treatment with

Introduction: Canine atopic dermatitis is a hereditary, often pruritic, and predominantly T-cell-driven inflammatory skin disease involving an interplay between skin barrier abnormalities and allergen sensitization. However, progress in developing therapeutics for companion animals remains slow, with few drugs advancing to Phase II clinical trials to investigate the underlying mechanisms in target animals. While Methods: In this study, RMFE was administered orally (repeatedly for 2 weeks) to ovalbumin (OVA)-induced atopic dermatitis-induced beagles. The effects of RMFE on cAD were assessed through clinical symptom observation and scoring using the canine atopic dermatitis extent and severity index. Additionally, histopathological analysis was performed (hematoxylin and eosin, Masson's trichrome, and toluidine blue). Cluster of differentiation 4-positive immunostaining was also performed, along with cytokine level and messenger ribonucleic acid level analyses of T-helper 2 (Th2) immune and inflammatory response markers in the modeled skin. Results: RMFE improved the clinical manifestations of cAD, leading to histopathological modulation of inflammation and immune cells. It also altered Th2 effector cytokine levels. Furthermore, RMFE reduced allergic responses in the AD model dogs by reducing mast cell numbers, inhibiting their activation to release inflammatory mediators, and reducing immunoglobulin E (IgE) production. Discussion: Our results suggest that RMFE can modulate mast cell activation and Th2-dominant immune responses in cAD, helping to reduce AD-induced inflammatory responses.