Atopic dermatitis (AD) is a chronic inflammatory skin condition with increasing prevalence. While various treatments exist, the need for novel and effective therapeutic strategies remains crucial. Coumarin derivatives, which are plant secondary metabolites, are known for their anti-inflammatory properties. However, their specific role and efficacy in treating AD have not been fully elucidated, prompting the investigation into the therapeutic potential of specific coumarin derivatives. This study specifically explores the potential of 7-geranyloxycoumarin (C#6) in alleviating AD-like symptoms by examining its multifaceted mechanisms of action.
Methods
This study utilized both in vitro and in vivo models to assess the efficacy of C#6. The in vitro experiments involved stimulated HaCaT cells, while the in vivo model employed MC903-induced AD in mice. Topical administration of C#6 was performed on the mice for a period of 10 days. The study further employed flow cytometry to analyze immune cell populations, 16S rRNA sequencing to assess changes in the skin microbiome, molecular docking studies to investigate interactions with inflammatory regulators, and co-culture experiments to understand immune-epidermal crosstalk.
Key Findings
•C#6 demonstrated remarkable efficacy in both in vitro and in vivo models of AD.
•Topical administration of C#6 significantly reduced ear and epidermal thickness in mice with AD-like symptoms.
•C#6 treatment led to a significant decrease in CD45+ leukocytes, eosinophils, and Th2 cells in the skin of AD mice.
•C#6 significantly suppressed the production of interleukin-8 (IL-8) and thymic stromal lymphopoietin (TSLP) in stimulated HaCaT cells.
•16S rRNA sequencing revealed that C#6 restored the disrupted skin microbiome by increasing the abundance of beneficial Lactobacillus and reducing pathogenic bacteria such as Enterobacteriaceae, Corynebacteriaceae, and Corynebacterium.
•Molecular docking studies indicated high binding affinities of C#6 to key inflammatory regulators, including NOD1, TLR2, PAR2, and TLR3, suggesting a role in modulating critical inflammatory pathways.
•Co-culture experiments showed that C#6 treatment suppressed the expression of inflammatory cytokines by THP-1 cells when co-cultured with TNF-α and IFN-γ-stimulated HaCaT cells.
This research provides compelling evidence for the therapeutic potential of 7-geranyloxycoumarin (C#6) in the management of atopic dermatitis. The novelty of this study lies in its demonstration of the multifaceted mechanisms by which C#6 alleviates AD-like symptoms, including the suppression of Th2-driven inflammation, reduction of eosinophilic infiltration, modulation of immune-epidermal crosstalk, and restoration of skin microbiome homeostasis. The findings highlight C#6 as a promising therapeutic agent for AD. Future implications of this research include further preclinical and clinical investigations to validate the safety and efficacy of topical C#6 for AD treatment in humans.
Link to the study: https://www.sciencedirect.com/science/article/pii/S0753332225001982
