Study of Artemisia ordosica Krasch. Against Allergic Rhinitis Based on the P815 Mast Cell Degranulation Model,...

Allergic rhinitis (AR) is one of the most prevalent allergic disorders worldwide. Current pharmacological treatments are often limited by suboptimal efficacy and notable adverse effects. Herbal medicines, with their multi-component and multi-target therapeutic characteristics, have attracted increasing attention. Artemisia ordosica Krasch. (AOK), a traditional Chinese/Mongolian medicine has demonstrated immunomodulatory, antioxidant, and anti-inflammatory activities. The anti-AR potential of AOK extract fractions was evaluated using in vitro mast cell degranulation inhibition assays, network pharmacology analysis, molecular docking, and molecular dynamics simulations to elucidate underlying pharmacological mechanisms. The P815 mast cell model induced by compound 48/80 was employed to assess the inhibitory activity and cytotoxicity of different extract fractions. Among the tested fractions, the ethyl acetate fraction exhibited the most potent inhibitory effect on mast cell degranulation without significant cytotoxicity. Network pharmacology analysis identified 254 potential AR-related targets of AOK, with Signal Transducer and Activator of Transcription 3(STAT3), Src protein(SRC), Tumor protein 53(TP53), AKT Serine/Threonine Kinase 1(AKT1), Heat Shock Protein 90 Alpha Family Class A Member 1(HSP90AA1), Estrogen Receptor 1(ESR1), and Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA) identified as key hub proteins. Gene Ontology and KEGG pathway enrichment analyses indicated that AOK primarily modulated inflammatory and oxidative stress-related processes through the lipid and atherosclerosis, hypoxia-inducible factor-1, and AGE-RAGE signaling pathways. Molecular docking and dynamics simulations demonstrated strong binding affinities and stable interactions between major active constituents, particularly hydroxygenkwanin, and key targets such as SRC. The ethyl acetate fraction of AOK extract exhibited significant mast cell degranulation inhibitory activity, likely mediated via a synergistic multi-component, multi-target mechanism involving regulation of inflammatory and immune-related signaling pathways. These findings provide a pharmacological basis for the potential application of AOK in AR treatment.