DIA-based quantitative proteomics reveal the protective effects of quercetin against atopic dermatitis via attenuating inflammation and modulating immune response

Abstract Atopic dermatitis is a common inflammatory skin disorder characterised by recurrent eczematous lesions and intense itch. Quercetin is a naturally occurring flavonoid, exhibits antioxidant and anti-inflammatory properties. Previous studies have indicated its beneficial role in managing atopic dermatitis (AD); however, the precise underlying mechanism remains unclear. This study aimed to investigate the protective effects of quercetin against AD and to elucidate its potential mechanisms. We demonstrated that quercetin effectively suppressed the overexpression of pro-inflammatory effector factors—including interleukin (IL)-1β, thymic stromal lymphopoietin (TSLP) and chemokine (C-X-C motif) ligand 1/10/11 (CXCL1/10/11)—in immortalized human keratinocytes (HaCaT) stimulated by TNF-α/IFN-γ. Proteomic analysis revealed 88 differentially expressed proteins, suggesting that quercetin’s therapeutic action involves multiple pathways. Notably, the NOD-like receptor signaling pathway was identified as a key factor. The key proteins related to this pathway including inhibitor of nuclear factor kappa B kinase epsilon (IKBKE), indoleamine 2,3-dioxygenase 1 (IDO1) and chemokine (C-X-C motif) ligand 9 (CXCL9) showed a significant decrease in expression levels after quercetin treatment. Collectively, these results demonstrate that quercetin alleviates AD symptoms by attenuating inflammatory responses, likely through inhibition of the NOD-like receptor signaling pathway.