Objective  To systematically explore the underlying mechanisms of Runzao Zhiyang capsule against atopic dermatitis (AD) using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), network pharmacology and molecular docking, and provide a scientific basis for its clinical use.

Methods  The chemical constituents in Runzao Zhuyao capsule were identified by UPLC-MS/MS. The SwissTargetPrediction platform was used to predict the component targets. The disease-related targets of AD were sourced from GeneCards, DisGeNET, and OMIM. The Venny 2.1.0 online tool was employed to obtain the intersection targets of drugs and diseases, and the “drug-component-disease-target” network diagram was further constructed with Cytoscape 3.9.0 software to identify the core active components. STRING database and Cytoscape 3.9.0 software were employed to build a protein-protein interaction (PPI) network and to screened out the core targets. DAVID was used for GO annotation and KEGG pathway enrichment analysis. Molecular docking further verified the binding activity between core components and targets.

Results  A total of 202 chemical components had been identified, with flavonoids, alkaloids, and phenolic acids accounting for over 50%. 370 intersecting targets between Runzao Zhiyang capsule and AD were obtained, and 10 key components including naringenin, isoquercetin, and quercetin were screened out. Twenty core targets such as TNF, AKT1, IL1B, and EGFR were screened out through the topological analysis of the PPI network. The KEGG pathway enrichment analysis showed that Runzao Zhiyang capsule mainly act on signaling pathways such as the AGE-RAGE signaling pathway, HIF-1 signaling pathway, and Th17 cell differentiation pathway, thus improving AD. Molecular docking simulation confirmed that the active components have good binding affinity with the core targets.

Conclusion  The identified key components in Runzao-Zhiyang capsules, such as genkwanin, isosinensetin, and morin, might improve AD by modulating core targets including TNF and AKT1 in the AGE-RAGE signaling pathway, thus providing directions and theoretical basis for the in-depth investigation of its underlying mechanisms.

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