Astaxanthin ameliorates allergic rhinitis via suppression of the HMGB1/TLR4 signaling pathway

Allergic rhinitis (AR) is a common inflammatory disease of the nasal mucosa mediated by immunoglobulin E (IgE). Astaxanthin (AST) has been demonstrated to attenuate airway inflammation in an asthmatic mouse model. Nonetheless, the precise effect of AST on AR symptoms and the associated mechanism remain unclear.

A mouse AR model was established by ovalbumin (OVA) sensitization and challenge, and AST was administered to AR mice. Human nasal epithelial cells (HNEpCs) were stimulated with recombinant human IL-13 to mimic the AR microenvironment in vitro. Hematoxylin-eosin staining was performed for mouse nasal mucosa histologic analysis. The CCK-8 assay was used to evaluate AST cytotoxicity to HNEpCs. ELISA was employed to determine levels of histamine, OVA-specific IgE, and inflammatory mediators. Oxidative stress-related markers were estimated using corresponding assay kits. Western blotting was implemented to estimate oxidative stress- and HMGB1/TLR4 signaling-related protein levels.

AST administration alleviated nasal symptoms, including sneezing and nasal rubbing, in OVA-triggered AR mice. AST mitigated nasal mucosa pathological damage, reduced histamine, OVA-specific IgE, and inflammatory mediators in the serum, and alleviated oxidative stress in the nasal mucosa of AR mice. AST blocked HMGB1/TLR4/NF-κB signaling transduction in both the nasal mucosa of AR mice and IL-13-treated HNEpCs. AST or TAK-242 (a TLR4 inhibitor) ameliorated inflammatory response and oxidative stress in IL-13-stimulated HNEpCs.

AST treatment ameliorates AR by reducing inflammation and oxidative stress via the HMGB1/TLR4/NF-κB pathway.