Mechanisms Underlying Ellagic Acid’s Effects on Improving Allergic Rhinitis based on Serum Untargeted Metabolomics Analysis

Abstract:

To investigate the therapeutic effects of ellagic acid (EA) on allergic rhinitis (AR) and its potential mechanisms of metabolic regulation, different doses of EA (4, 8, and 16 mg.kg-1) were administered to ovalbumen-induced AR rats. Pathological changes in nasal mucosa and lung tissue were observed, levels of IgE, histamine, IL-4, and IL-6 in serum were measured, and metabolite changes along with their correlations with allergic inflammation markers were analyzed using untargeted metabolomics. The results showed that EA interventions reduced the number of mast cells in the nasal mucosa and lung tissue and decreased the levels of IgE, histamine, IL-4, and IL-6 in the serum, with the high-dose group showing the most significant improvements (reductions of 26.40%, 23.79%, 21.65%, and 35.00% in the abovementioned indicators, respectively). Untargeted metabolomics identified 43 differential metabolites, among which 22 were significantly restored after intervention (P<0.05), including 19 metabolites positively correlated and 3 negatively correlated with allergic inflammation markers. Enrichment analysis revealed that the restored metabolites were significantly enriched in three pathways: arachidonic acid metabolism, primary bile acid biosynthesis, and porphyrin metabolism. In conclusion, EA alleviates AR by improving pathological tissue conditions, reducing allergic inflammation markers, and regulating key metabolic pathways. These findings provide new insights into the application of EA and related polyphenols in the development of anti-allergic functional foods.