Polyphenols and Cannabidiol Modulate Transcriptional Regulation of Th1/Th2 Inflammatory Genes Related to Canine Atopic Dermatitis

Canine atopic dermatitis (AD) is a multifactorial allergic disease associated with immune and abnormal skin barrier dysfunction and it is one of the primary causes of pruritus. Using a novel in vitro model of AD, here we tried to revert the alteration of transcriptional regulation of AD canine key genes testing a nutraceutical mixture containing flavonoids, stilbene, and cannabinoids, which are already well-known for their applications within dermatology diseases. The nutraceutical mixture induced in inflamed cells a significant downregulation (p < 0.05) of the gene expression of ccl2, ccl17, and tslp in keratinocytes and of ccl2, ccl17, and il31ra in monocytes. Consistent with the observed alterations of tslp, ccl2, ccl17, and il31ra messenger RNA (mRNA) levels, a significant increase (p < 0.05) of DNA methylation at specific CpG sites on the gene regulatory regions was found. These results lay the foundation for the use of these natural bioactives in veterinary medicine and provide a model for deeper understanding of their mechanisms of action, with potential translation to human research.