Protective effects of astragaloside IV against ovalbumin-induced allergic rhinitis are mediated by T-box protein expressed in T cells/GATA-3 and forkhead box protein 3/retinoic acid-related orphan nuclear receptor gamma t

摘要

3O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosyl-cycloastragenol, or Astragaloside IV (AST), is one of the major active ingredients isolated from Astragalus membranaceous with distinct pharmacological effects, and possesses anti-inflammatory, immunoregulatory and antifibrotic properties. However, the effects of AST on allergic rhinitis remain to be elucidated. The present study aimed to examine the effects of AST on immunoglobulin (Ig) E-mediated allergic reactions in vivo, by using a mouse model of allergic rhinitis established via repetitive sensitization and intranasal challenge with ovalbumin (OVA). Intragastric administration of AST (25 mg/kg or 50 mg/kg) or dexamethasone (DEX; 3 mg/kg) significantly alleviated the inflammatory response, nasal symptoms and mucosa remodeling, and decreased the serum levels of OVA-specific IgE in allergic mice. Furthermore, treatment with AST or DEX significantly suppressed the mRNA and protein expression levels of the transcription factor GATA-3 and retinoic acid receptor-related orphan nuclear receptor (ROR)gamma t in tissue samples isolated from the spleen and nasal mucosa of mice with allergic rhinitis. Conversely, mRNA and protein expression levels of T-box protein expressed in T cells (T-bet) and forkhead box protein 3 (Foxp3) were upregulated in the spleen and nasal mucosa of mice with allergic rhinitis following treatment with AST or DEX, and spleen protein levels of signal transducer and activator of transcription 3 followed a similar trend. In addition, treatment with AST was associated with fewer adverse events compared with treatment with DEX. The present results suggested that treatment with AST may attenuate OVA-induced allergic rhinitis via regulating the expression of the transcription factors GATA-3, ROR gamma t, T-bet and Foxp3, which commit T helper cells to the Th1 phenotype. Therefore, AST may represent an alternative therapeutic approach for the treatment of patients with allergic rhinitis.