Comparing the Effects of Korean and Brazilian Propolis on Anti-Atopic Dermatitis and the Related Mechanisms Through In Silico and In Vitro Analyses

Atopic dermatitis (AD) is a chronic inflammatory skin disorder requiring continuous care and treatment. Therefore, exploring the therapeutic potential of natural ingredients for AD is essential. This study conducted a network analysis to investigate the anti-AD effects of propolis and its underlying mechanism, with a focus on the compositional differences between Korean and Brazilian propolis. To identify the bioactive components and related mechanisms, differentially expressed genes (DEGs) in AD-induced HaCaT cells with and without propolis treatment were identified. NCBI, SwissTargetPrediction, STITCH, and the Comparative Toxicogenomics Database (CTD) were used to identify target genes of the propolis compounds, and these genes were compared with the DEGs to identify the shared target genes. Notably, CXCL10 and CCL2 were highly associated with target genes shared between Korean and Brazilian propolis, with Korean propolis affecting TLR4, RIPK2, and PYCARD and Brazilian propolis influencing CEBPB, PTGS2, and DAB2IP. Korean propolis was found to predominantly impact the regulation of mast cell activation and the cytosolic DNA-sensing pathway, whereas Brazilian propolis primarily affects Type I interferon–mediated regulation and the TNF signaling pathway. Additionally, both the TNF and IL-17 signaling pathways were implicated in the mechanisms of both Brazilian propolis and Korean propolis. Furthermore, our study validated the therapeutic potential of propolis in AD treatment, as evidenced by significant reductions in TNF-α, IFN-γ, IL-4, IL-13, CXCL10, CCL2, and histamine release in an AD-induced model. This study confirms the efficacy of Korean and Brazilian propolis in treating AD and reveals molecular mechanism differences due to variations in major components and target genes.