Objective  To elucidate the molecular mechanisms of Xianju Xiaozhen decoction (XXD) on atopic dermatitis (AD) using a systematic pharmacology approach.

Methods  The bioactive components and potential targets of XXD were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). AD-related target genes were obtained from the GeneCards database. Venn analysis was performed to identify the overlapping targets between XXD and AD. A protein-protein interaction network was constructed using data from the STRING database and Cytoscape 3.9.1, and key regulatory targets were identified through topological analysis. Gene function and pathway enrichment analyses were conducted. Furthermore, molecular docking was used to evaluate the binding affinity between the active components and core targets, validating their interactions from the three-dimensional structural level.

Results  A total of 35 active components and 695 corresponding targets of XXD were identified. Among these, the four most prominent compounds based on degree centrality were quercetin, luteolin, kaempferol, and arachidonic acid. Additionally, 4,682 AD-related targets were identified, with 177 overlapping targets between XXD and AD. Core targets included PTGS2, PTGS1, HSP90AA1, and DPP4. Functional enrichment analysis indicated that these targets were primarily involved in biological processes such as responses to xenobiotic stimuli, nuclear receptor activity, transcription factor regulation, and vesicle lumen processes. The associated signaling pathways were mainly the TNF signaling pathway, PI3K-Akt signaling pathway, and IL-17 immune signaling pathway. Molecular docking results demonstrated that the binding energies of the core targets with the four major active components were all lower than -5 kcal/mol, with luteolin exhibiting the strongest binding affinity to PTGS2 and HSP90AA1.

Conclusion  The active components of XXD may exert therapeutic effects on AD through a multi-target, multi-pathway synergistic mechanism. This study provides a theoretical basis for further experimental investigations and clinical applications of XXD in AD treatment.

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