P2 Receptors as Therapeutic Targets in Allergic Rhinitis: Insights From the Use of Natural Products and Preclinical...

Allergic rhinitis (AR) is a chronic inflammatory disorder of the upper airways that is mediated by immunoglobulin E (IgE) and triggered by environmental allergens. Current pharmacological therapies, including antihistamines, corticosteroids, and immunotherapy, offer symptomatic relief but are limited by their incomplete disease-modulating effects and potential adverse side effects. Purinergic P2 receptors (P2Rs; P2X and P2Y subtypes) have emerged as key modulators of allergic inflammation and regulate mast cell degranulation, T helper 2 (Th2) cytokine release, eosinophil recruitment, and NLRP3 inflammasome activation. Natural products, including polyphenols, flavonoids, terpenoids, and alkaloids, demonstrate multitarget anti-inflammatory effects and have the potential to modulate P2R signaling. However, direct evidence of their activity on P2Rs in AR remains limited. This review critically summarizes the immunopathology of AR, highlights the functional relevance of P2Rs, and discusses emerging natural product-based strategies, emphasizing mechanistic insights and translational potential for the development of novel therapeutics.