Identification of potential targets and mechanisms of Mahuang in treating allergic rhinitis via network pharmacology and bioinformatics

Allergic rhinitis (AR) is an inflammatory condition caused by nasal mucosal injury. Mahuang, a traditional Chinese medicine used for colds and asthma, also shows promise in AR treatment, but its mechanism is unclear. Potential targets of Mahuang and AR were retrieved from the traditional chinese medicine systems pharmacology database (TCMSP), GeneCards, the therapeutic target database (TTD), and online mendelian inheritance in man (OMIM). Cytoscape was used for network visualization and analysis. Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analyses and visualizations were performed using SangerBox. Molecular docking was carried out with AutoDock Vina (v 1.2.7), and molecular interactions were visualized with PyMOL (v 3.0) and Discovery Studio 4.5 Client, respectively. Cell viability was assessed by cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) levels and intracellular Cu 2 + content were assessed using commercial kits, and protein expression was analyzed by Western blot. After screening, a total of 22 active compounds of Mahuang are obtained, including quercetin (Que), luteolin, and naringenin. A total of 227 Mahuang-related genes and 2693 AR-related genes are identified, among which 122 overlapping targets are found. These genes are enriched in the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) signaling pathway and pathways related to cell proliferation. Although the role of cuproptosis in AR remains unclear, analyzing cuproptosis-related genes helps identify potential therapeutic targets. We further analyze 50 known cuproptosis-related genes and find that cyclin-dependent kinase inhibitor 2 A (CDKN2A) and serpin family E member 1 (SERPINE1) overlap with the 122 overlapping targets, suggesting that they may play a role in the pathological process of AR. Que is identified as a key active compound that may act on CDKN2A and SERPINE1. In vitro experiments show that Que increases the viability of Particulate Matter 2.5 (PM2.5)-induced human nasal mucosal epithelial cells (HN-MECs), reduces LDH levels, decreased the protein expression of CDKN2A and SERPINE1, and lowered the intracellular Cu 2+ content. These results suggest Mahuang may alleviate AR by modulating cuproptosis-related genes CDKN2A and SERPINE1, with Que as a key active component. • Network pharmacology and bioinformatics identify key targets of Mahuang related to allergic rhinitis. • Cuproptosis-related genes CDKN2A and SERPINE1 are potential targets of Mahuang. • Quercetin is the main active compound of Mahuang. • Experimental validation shows quercetin regulates PM2.5-induced human nasal mucosal epithelial cell injury. • Quercetin regulates cuproptosis gene expression, revealing therapeutic mechanisms.