Introduction Atopic eczema (AE) is a chronic inflammatory skin disease involving complex immune interactions. Paeoniflorin, a compound from traditional Chinese medicine, has anti‐inflammatory and immune‐regulating properties. This study explores how paeoniflorin affects AE, focusing on its regulation of the MYC protein, associated T cell pathways, and the epithelial immune response. Methods Potential targets of paeoniflorin were identified using multiple databases, followed by functional enrichment analysis. Gene expression data from GEO were analyzed to find differentially expressed genes (DEGs). Weighted gene coexpression network analysis (WGCNA) identified key AE‐related genes. A diagnostic model was built using Lasso regression and validated with internal and external datasets. Single‐cell RNA sequencing mapped key gene expression in cell subsets. Molecular docking and dynamics simulations evaluated the binding of paeoniflorin to target proteins. In vitro experiments confirmed the biological effects of paeoniflorin on protein expression and cell function. Results A total of 312 potential targets of paeoniflorin were found, mainly related to Wnt signaling and cell communication pathways. DEGs from the GSE6012 dataset included 614 upregulated and 684 downregulated genes. WGCNA identified 1443 hub genes, with five core genes (including MYC and TOP2A). The diagnostic model showed good predictive power, with AUC values over 0.80 for MYC and TOP2A. Single‐cell analysis revealed a distinct expansion of T cell populations characterized by low MYC expression in AE lesions, highlighting the complex immune landscape. In parallel, paeoniflorin showed stable binding to MYC and TOP2A. In vitro, paeoniflorin mitigated inflammation‐induced epithelial dysfunction by downregulating aberrant MYC overexpression and upregulating PPARγ in keratinocytes. Conclusion Paeoniflorin shows potential to alleviate AE‐associated epithelial dysfunction by modulating the MYC/PPARγ axis. These findings provide mechanistic insights supporting paeoniflorin as a promising candidate for AE therapy.
Zhang et al. (Thu,) studied this question.