Oral treatment with Rosa multiflora fructus extract attenuated the inflammatory effects of mast cells in ovalbumin-induced atopic dermatitis

Ha-young Shin ^1,2 Sang Hun Shin ³ Hee Soon Shin ^4,5 Hyun-Jin Tae ² Hyun-Jin Kim ^6,7 Jeong Ho Hwang ^1,3*

• ¹ Center for Large Animals Convergence Research, Korea Institute of Toxicology, Jeongeup, North Jeolla, Republic of Korea
• ² Department of Veterinary Medicine, College of Veterinary Medicine and Institute of Animal Transplantation, Jeonbuk National University, Iksan, Republic of Korea
• ³ Center for Companion Animal New Drug Development, Korea Institute of Toxicology, Jeongeup, North Jeolla, Republic of Korea
• ⁴ Research Division of Food Functionality, Korea Food Research Institute, Wanju, Republic of Korea
• ⁵ Department of Food Biotechnology, University of Science and Technology, Daejeon, Republic of Korea
• ⁶ Department of Food Science and Technology, Jinju, Republic of Korea
• ⁷ EZmass. Co. Ltd, Jinju, Republic of Korea

Introduction: Canine atopic dermatitis is a hereditary, typically pruritic and predominantly T-cell driven inflammatory skin disease involving interplay between skin barrier abnormalities, allergen sensitization. However, progress in developing therapeutics for companion animals remains slow, and few companion animal drugs have undergone Phase II clinical trials to investigate the underlying mechanisms in target animals. While Rosa multiflora fruit extract (RMFE) has been strongly implicated in the improvement of various inflammatory diseases, its effects on cAD and the putative underlying mechanisms remain unclear. In this study, we aimed to evaluate the efficacy of RMFE in the treatment of cAD and explore its underlying mechanisms. Methods: In this study, we administered RMFE orally repeatedly for 2 weeks to ovalbumin-induced atopic dermatitis-induced beagles. The effects of RMFE on cAD were assessed through clinical symptom observation and scoring (canine atopic dermatitis extent and severity index), histopathological analysis (hematoxylin and eosin, Masson's trichrome, and toluidine blue) and cluster of differentiation 4-positive immunostaining, and cytokine level and messenger ribonucleic acid level analyses of T-helper 2 (Th2) immune and inflammatory response markers in modeled skin. Results: RMFE improved clinical manifestations of cAD, induced histopathological modulation of inflammation and immune cells, and altered Th2 effector cytokine levels. RMFE also reduced allergic responses in AD model dogs by reducing mast cell numbers, inhibiting their activation to release inflammatory mediators, and reducing immunoglobulin E production. Discussion: Our results suggest that RMFE can modulate mast cell activation and Th2-dominant immune responses in cAD, helping to reduce ADinduced inflammatory responses.