Acesulfame Potassium Alleviates Food Allergy via Mast Cell Stabilization and MAPK-Mediated Immune Regulation

Acesulfame potassium (AK), a widely used synthetic non-nutritive sweetener in low-calorie food and beverage products, has not been comprehensively investigated for its potential modulatory effects on food allergies. This study systematically investigated the therapeutic potential of AK using both an ovalbumin (OVA)-induced murine food allergy model and IgE/BSA-activated RBL-2H3 mast cells. <i>In vivo</i> experiments demonstrated that AK administration during OVA sensitization significantly alleviated allergic manifestations, showing a 78% reduction in diarrhea incidence and systemic anaphylactic scores compared with those of the OVA-sensitized controls. Serum biomarker analysis revealed that AK effectively suppressed the production of allergy-related mediators, including IgE, IgG1, histamine, and β-hexosaminidase. Histopathological examination indicated preserved duodenal architecture with increased villus height. Mechanistically, AK restored immune homeostasis by rebalancing Th1/Th2 and Th17/Treg responses while suppressing Th2- and Th17-associated cytokine production. <i>In vitro</i> experiments demonstrated that AK dose-dependently inhibited mast cell degranulation and suppressed the secretion of pro-inflammatory cytokines (IL-4, IL-6, and IL-13). Western blot analysis further revealed that AK significantly suppressed the MAPK signaling pathway in activated mast cells, with reductions of 60% in p-JNK, 57% in p-ERK, and 64% in p38 phosphorylation. These findings elucidate that AK exerts dual protective effects through both mast cell stabilization and systemic immunomodulation, proposing its potential incorporation into hypoallergenic diets. The study provides novel insights into food additives' capacity to regulate hypersensitivity reactions, with implications for developing functional foods targeting immune-mediated disorders.