Bruceine D ameliorates the balance of Th1/Th2 in a mouse model of ovalbumin-induced allergic asthma via inhibiting the NOTCH pathway.

Abstract

Allergic asthma is a heterogeneous inflammatory disorder triggered by inhaled allergens, leading to airflow obstruction, bronchial inflammation, and airway hyperresponsiveness (AHR). T helper (Th) 2 cell-mediated immune response and airway inflammation are the key features of allergic asthma. Bruceine D (BD) is a bioactive compound extracted from the seeds of Brucea javanica. The present study aimed to investigate the effects of increased doses of BD on AHR, secretion of Th1-/Th2-associated cytokines, and inflammatory cell infiltration in ovalbumin (OVA)-induced allergic asthma mice. The results showed that BD reduced OVA-induced inflammatory cell infiltration and bronchial hyperresponsiveness into the peribronchial tissues and perivascular areas. Mice treated with BD also showed significantly decreased expressions of Th2-associated cytokines (i.e., interleukin (IL)-4, IL-5, and IL-13) and elevated production of Th1-associated cytokines (i.e., interferon gamma and IL-2) following OVA stimulation. BD treatment dose-dependently inhibited OVA-induced accumulation of inflammatory cells in asthmatic mice. Further analysis revealed that OVA exposure upregulated pulmonary expressions of NOTCH signaling receptors, a group of transmembrane proteins that communicate signals upon binding to transmembrane ligands expressed on adjacent cells, while BD treatment significantly abolished OVA-induced activation of the NOTCH pathway. In conclusion, BD protected mice against OVA-induced allergic asthma by reducing AHR and restoring the Th1/Th2 balance through the NOTCH signaling pathway. Our findings highlighted the potential of BD as a therapeutic agent for allergic asthma.

• Authors: Ying Nie, Bangkun Yang, Junfeng Hu, Lingling Zhang, Zhimin Ma
• Journal: Allergologia et immunopathologia (Allergol Immunopathol (Madr)) Vol. 49 Issue 6 Pg. 73-79 ( 2021) ISSN: 1578-1267 [Electronic] Singapore
• PMID: 34761661 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Quassins
• Receptors, Notch
• bruceine D
• Ovalbumin

Topics

• Animals
• Asthma (chemically induced, drug therapy)
• Bronchoalveolar Lavage Fluid
• Brucea javanica
• Cytokines
• Disease Models, Animal
• Inflammation
• Lung
• Mice
• Mice, Inbred BALB C
• Ovalbumin
• Quassins (pharmacology)
• Receptors, Notch (metabolism)
• Th1-Th2 Balance (drug effects)