d-Limonene inhibits cytokines and chemokines expression by regulating NF-kappaB and STAT in HaCat cells and DNCB-induced atopic dermatitis in BALB/c mice

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by itching and redness, affecting individuals of all ages and significantly impairing their quality of life. The prevalence of AD is rising, posing serious health concern. Relief of itching is a primary treatment objective; however, steroid treatments can lead to adverse effects, including skin barrier thinning. Therefore, there is a pressing need for safer therapeutic alternatives. Limonene, a naturally occurring monocyclic monoterpene found in citrus peel oil, is widely utilized in food, cosmetics, and pharmaceuticals. Research has identified various biological activities of limonene, including antioxidative, anti-inflammatory, immunomodulatory, and antifibrotic properties. This study aims to investigate the therapeutic effects of limonene on atopic dermatitis, focusing on its anti-inflammatory potential.

Methods: In this study, we investigated the expression levels of pro-inflammatory cytokines and chemokines, conducting histopathological analyses, and collecting physiological data from BALB/c mice with atopic-like dermatitis induced by 2,4-dinitrochlorobenzene (DNCB) and TNF-α/ IFN-γ-stimulated HaCaT cells.

Results: In vitro studies indicated that limonene inhibited cytokine and chemokine expression in human keratinocytes and reduced phosphorylation in the MAPK, NF-κB, and JAK/STAT signaling pathways. In vivo, limonene mitigated DNCB-induced skin barrier damage and itching, improving physiological parameters such as trans-epidermal water loss, erythema, and ear thickness. Furthermore, it decreased the mRNA expression of pro-inflammatory cytokines.

Conclusion: Limonene exhibits significant anti-inflammatory effects, highlighting its therapeutic potential for treating atopic dermatitis.