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 γt.

Abstract

3-O-β-D-xylopyranosyl-6-O-β-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)γt 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, RORγt, 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.

• Authors: Keqiong Li, Yi Chen, Rong Jiang, Dilong Chen, Hong Wang, Wei Xiong, Danyang Li, Zehong Liu, Xiaopeng Li, Jing Li, Ke Yuan
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 16 Issue 2 Pg. 1207-1215 (Aug 2017) ISSN: 1791-3004 [Electronic] Greece
• PMID: 28586019 (Publication Type: Journal Article)

Chemical References

• Allergens
• Biomarkers
• DNA-Binding Proteins
• GATA3 Transcription Factor
• Nerve Tissue Proteins
• NeuN protein, mouse
• Nuclear Proteins
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Protective Agents
• RNA, Messenger
• Saponins
• T-Box Domain Proteins
• Triterpenes
• Immunoglobulin E
• astragaloside A
• Dexamethasone
• Ovalbumin

Topics

• Allergens (immunology)
• Animals
• Biomarkers
• DNA-Binding Proteins
• Dexamethasone (pharmacology)
• Disease Models, Animal
• Female
• GATA3 Transcription Factor (metabolism)
• Gene Expression Regulation (drug effects)
• Immunoglobulin E (blood, immunology)
• Male
• Mice
• Nasal Mucosa (immunology, metabolism)
• Nerve Tissue Proteins (metabolism)
• Nuclear Proteins (metabolism)
• Nuclear Receptor Subfamily 1, Group F, Member 3 (metabolism)
• Ovalbumin (adverse effects)
• Protective Agents (pharmacology)
• RNA, Messenger (genetics, metabolism)
• Rhinitis, Allergic (diagnosis, drug therapy, etiology, metabolism)
• Saponins (pharmacology)
• Spleen (immunology, metabolism)
• T-Box Domain Proteins (genetics)
• T-Lymphocyte Subsets (immunology, metabolism)
• Triterpenes (pharmacology)