Protocatechuic acid supplement alleviates allergic airway inflammation by inhibiting the IL-4Rα-STAT6 and Jagged 1/Jagged2-Notch1/Notch2 pathways in allergic asthmatic mice

Inflamm Res. 2020 Oct;69(10):1027-1037. doi: 10.1007/s00011-020-01379-1. Epub 2020 Jul 15.

Abstract

Objective and design: To clarify the effects of dietary supplementation of protocatechuic acid (PCA) and in-depth mechanisms on allergic asthma in ovalbumin (OVA)-induced mice.

Materials: Female BALB/c mice were randomly divided into three groups (n = 10 in each group): control group, OVA-induced allergic asthma group, and OVA plus PCA group.

Treatment: Dietary supplementation of PCA was achieved by adding 50 mg/kg PCA to AIN 93G diet for 25 days.

Methods: Peripheral blood cells, pulmonary inflammatory cell infiltration, the levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), the mRNA levels of Th2-related genes in the lungs, and the protein expressions of the IL-4Rα-STAT6 and the Jagged1/Jagged2-Notch1/Notch2 signaling pathways were measured.

Results: Significantly reduced inflammatory cells infiltration and mucosal hypersecretion in the lung tissues, repaired levels of interleukin IL-4, IL-5, and IL-13 in the BALF, and decreased mRNA expression of IL-4, IL-5, and GATA3 were observed in OVA plus PCA group. Moreover, PCA treatment down-regulated the protein levels of IL-4Rα-STAT6 and Jagged1/Jagged2-Notch1/Notch2 signaling pathways.

Conclusions: Dietary supplement of PCA alleviated allergic asthma partly through suppressing the IL-4Rα-STAT6 and Jagged1/Jagged2-Notch1/Notch2 signaling pathways in mice. Our study provided the theoretic basis of PCA used as functional food in preventing allergic asthma.

Keywords: Airway inflammation; Allergic asthma; Notch; Protocatechuic acid; STAT6; Th2 response.

MeSH terms

  • Allergens
  • Animals
  • Asthma / diet therapy*
  • Asthma / genetics
  • Asthma / immunology
  • Asthma / pathology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / genetics
  • Cytokines / immunology
  • Dietary Supplements*
  • Female
  • Functional Food
  • Hydroxybenzoates / therapeutic use*
  • Jagged-1 Protein / immunology
  • Jagged-2 Protein / immunology
  • Leukocyte Count
  • Lung / immunology
  • Lung / pathology
  • Mice, Inbred BALB C
  • Ovalbumin
  • Receptor, Notch1 / immunology
  • Receptor, Notch2 / immunology
  • Receptors, Cell Surface / immunology
  • STAT6 Transcription Factor / immunology
  • Signal Transduction

Substances

  • Allergens
  • Cytokines
  • Hydroxybenzoates
  • Il4ra protein, mouse
  • Jagged-1 Protein
  • Jagged-2 Protein
  • Notch1 protein, mouse
  • Notch2 protein, mouse
  • Receptor, Notch1
  • Receptor, Notch2
  • Receptors, Cell Surface
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • protocatechuic acid
  • Ovalbumin