Mechanistic Evaluation of EGCG against Atopic Dermatitis: An <i>in Vivo</i> and <i>in Silico</i> Study

Background: Atopic dermatitis, often referred to as AD, is a common chronic and relapsing skin disease with few treatment options. Epigallocatechin 3-gallate (EGCG), the most abundant catechin derived from green tea, has gained widespread attention due to its excellent anti-inflammatory and anti-oxidative properties. This research aims to investigate the effect and mechanism of EGCG in alleviating AD by integrative approach of an in vivo AD mouse model, network pharmacology and molecular docking. Materials and Methods: EGCG was administered by intragastric administration at the dose of 100 mg/kg, once daily for 14 consecutive days to AD mice, a model established by repeated application of 2, 4-dinitrofluorobenzene (DNFB) to the mouse dorsal skin. Results: Macroscopical and histopathological examination showed that oral administration with EGCG could markedly relieve AD-like skin phenotypes, as evidenced by a substantial reduction in severity score, serum immunoglobulin E (IgE) level, epidermal thickness, and the infiltration of inflammatory cells and mast cells into the dermal layers. Mechanistically, the network pharmacology analysis indicated that the protective effects of EGCG against AD were mainly related to the regulation of AGE-RAGE signaling pathway in diabetic complications, Th17 cell differentiation, IL-17 signaling pathway, NF-κB signaling pathway, Toll-like receptor signaling pathway, TNF signaling pathway, etc. In silico molecular docking demonstrated the high binding affinity of EGCG to the core targets such as ABCB1, MMP2, MMP9, MAPK14 and STAT1. Furthermore, western blotting (WB) results showed that EGCG obviously downregulated the expression of RAGE and STAT1, thereby regulating the AGE-RAGE signaling pathway to improve AD. Conclusions: These findings indicated that EGCG can be a promising therapeutic candidate for AD.