Mechanism of Rosmarinic Acid in Alleviating Food Allergy Based on Network Pharmacology and Lipidomics

To investigate the mechanism of rosmarinic acid in alleviating food allergy, an integrated approach, involving network pharmacology, molecular docking and lipid-omics were employed to investigate the potential mechanism of rosmarinic acid (RA) in alleviating food allergy. To obtain potential therapeutic targets for RA, database analysis platform such as database and analysis platform (TCMSP), Swiss Target Prediction, Pharm Mapper, Super Pred and Gene Cards were employed. The ''active ingredient-target'' protein-protein (PPI) network was constructed using Cytoscape software and the String database. The validation of molecular docking was performed using AutoDockTools software. Furthermore, a food allergy mouse model using ovalbumin (OVA) and lipid metabolism studies on mouse serum based on high-resolution mass spectrometry were applied to investigate the antiallergic effect of RA and the underling mechanism. Results showed that, through the network pharmacology analysis, a total of 46 associated target proteins were identified. The geno ontology (GO) enrichment analysis of the target proteins indicated that RA primarily exerted its effects through modulation of protein phosphorylation and the binding between glycosphingolipids, phospholipids and steroids. The kyoto encyclopedia of genes and genomes (KEGG) analysis indicated that the associated targets were mainly enriched in the Th1/Th2 cell differentiation pathways, lipid metabolism and inflammatory bowel disease pathways. The results indicated that RA intervention could significantly suppress the elevation of allergic mediators in the serum of mice sensitizes with OVA. In addition, the RA intervention group showed a decrease in the levels of total cholesterol and triglycerides in the mouse serum. In lipidomics analysis, 25 and 36 differentially expressed lipid metabolites were screened in positive and negative ion modes, respectively. Enrichment analysis of the differentially expressed lipid metabolites indicated that the serum lipid metabolism in mice affected glycerophospholipid metabolism and sphingolipid metabolic pathways. Therefore, this study demonstrated that RA primarily exerted its alleviating effect on food allergies by regulating lipid metabolism and the body's inflammatory response.