Mechanism of Artemisia annua active component quercetin in treating psoriasis by regulating ferroptosis

This study aimed to investigate the mechanism by which active components of Artemisia annua modulate ferroptosis in the treatment of psoriasis vulgaris through an integrated approach combining network pharmacology, molecular docking, and in vivo validation. Therapeutic targets of Artemisia annua active components and psoriasis vulgaris-related genes were retrieved from the TCMSP and GeneCards databases, respectively. Common targets were identified using Venn analysis. Protein-protein interaction (PPI) networks were constructed using Cytoscape, with core targets extracted via the CytoHubba plugin. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Ferroptosis-related genes were acquired from the FerrDb database. Molecular docking assessed the binding affinity between key active components and critical targets. In vivo experiments using an imiquimod (IMQ)-induced psoriasis-like mouse model were conducted to validate the network pharmacology predictions. Network pharmacology identified 22 active components of Artemisia annua, 202 potential targets, and 1,312 psoriasis-related genes, yielding 96 common targets. Further analysis revealed 485 ferroptosis-related genes, with 26 overlapping targets associated with 17 active components. PPI network analysis indicated TP53(P53), IL6, and IL1B as core targets. Quercetin, kaempferol, and luteolin were identified as the primary active components. Molecular docking demonstrated strong binding affinity between quercetin and TP53(P53). In vivo experiments showed that quercetin significantly alleviated psoriatic-like skin lesions, increased epidermal glutathione (GSH) levels, reduced Fe²⁺ accumulation and reactive oxygen species (ROS) production, and improved mitochondrial morphology. Furthermore, quercetin downregulated the protein and mRNA expression of P53, SAT1, and ALOX15. This study demonstrates that quercetin is the major active component of Artemisia annua responsible for mediating epidermal ferroptosis in psoriasis treatment. Experimental results indicate that quercetin alleviates the inflammatory response in psoriasis by inhibiting epidermal ferroptosis, a process that may be associated with the regulation of the P53/SAT1/ALOX15 signaling pathway.