Angelica dahurica Exosome-like Nanovesicles Delivered by Ultrasonic Nebulization Alleviate Allergic Rhinitis and Modulate NF-κB Signaling

Background: Current treatments for allergic rhinitis (AR) are associated with side effects and do not provide a definitive cure. Angelica dahurica has recognized anti-inflammatory activity; however, the therapeutic potential of Angelica dahurica-derived exosome-like nanovesicles (ADELNs) in AR remains insufficiently explored. In addition, although ultrasonic nebulization is widely used for airway inflammatory diseases, including pulmonary disorders and asthma, its application in AR has received limited attention. Methods: ADELNs were isolated by differential centrifugation and ultracentrifugation and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), thin-layer chromatography (TLC), SDS-PAGE, and agarose gel electrophoresis. To evaluate the effects of ultrasonic nebulized ADELNs on AR, we designed and validated a mouse nasal nebulization device. Cellular inflammation and OVA-induced AR mouse models were then established, and inflammatory and pathological indicators were assessed using ELISA, RT-qPCR, histological staining, and related assays. Western blotting was used to investigate the involvement of the NF-κB signaling pathway. Result: ADELNs were successfully isolated and exhibited typical exosome-like characteristics. The ultrasonic nebulization device showed good stability. Nebulized ADELNs alleviated AR symptoms in mice in a concentration-dependent manner, reduced inflammatory cytokines, serum histamine, and OVA-specific IgE, downregulated inflammatory cytokine mRNA expression in the nasal mucosa, improved nasal mucosal thickness, and decreased mast cell infiltration. To explore the potential mechanism, ADELN treatment was associated with reduced IκB and p65 phosphorylation and decreased NF-κB nuclear translocation, suggesting that modulation of NF-κB signaling may contribute to the anti-inflammatory effects of ADELNs. Conclusions: This study successfully isolated and characterized ADELNs. Using a self-designed ultrasonic nebulization device for mouse nasal delivery, we showed that ADELNs inhibited cellular inflammation in vitro, alleviated symptoms and pathological injury in AR mice, and may exert anti-AR effects by suppressing the NF-κB signaling pathway. These findings provide a new strategy for AR treatment.