Geraniol alleviates DNCB-induced atopic dermatitis in mice by downregulating IL-4/IL-13 and reducing inflammation

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by recurrent itching, predominantly affecting children but also impacting adults. Geraniol, a monoterpene alcohol found in various aromatic plant-based essential oils, possesses a pleasant rose-like scent. This study aimed to investigate the therapeutic potential of geraniol in a mouse model of atopic dermatitis by elucidating its anti-inflammatory and immunomodulatory properties. Mice were subjected to 2% 2,4-Dinitrochlorobenzene (DNCB) to induce AD, and treated with both oral and topical administrations of prednisolone and geraniol from day 7 to day 19. Macroscopic assessments of ear and dorsal skin, as well as ear thickness, were conducted on days 0, 7, and 19. Total leukocyte count (TLC) and differential leukocyte count (DLC) were measured in blood samples using an automatic hematology analyzer. Ear tissues were analyzed for mRNA expression levels of IL-4 and IL-13 via reverse transcription quantitative polymerase chain reaction (RT-qPCR), and molecular docking studies were performed to evaluate the binding affinity of geraniol to these cytokines. Histopathological examination using hematoxylin and eosin staining was conducted on ear and dorsal skin tissues to assess eosinophil and mast cell infiltration, as well as epidermal thickness. The results demonstrated that both oral and topical geraniol significantly alleviated AD-like symptoms. Geraniol treatment led to a reduction in DLC and TLC levels in the blood, as well as downregulation of IL-4 and IL-13 expression in ear tissue. In silico studies revealed that geraniol exhibited moderate binding affinities of -4.5 kcal/mol with IL-4 and -4.9 kcal/mol with IL-13. Histopathological analysis indicated a reduction in epidermal thickness and infiltration of mast cells and eosinophils in geraniol-treated mice. In conclusion, geraniol effectively alleviated atopic dermatitis in mice by reducing clinical scores, inflammatory cell infiltration, epidermal thickening, and regional downregulation of IL-4 and IL-13 mRNA expression. The in silico docking studies support the hypothesis of a potential Th2-modulatory effect of geraniol.