Amygdalin Improves Allergic Asthma via the Thymic Stromal Lymphopoietin-dendritic Cell-OX40 Ligand Axis in a Mouse Model

Iran J Allergy Asthma Immunol. 2023 Oct 29;22(5):430-439. doi: 10.18502/ijaai.v22i5.13993.

Abstract

Asthma, characterized by persistent inflammation and increased sensitivity of the airway, is the most common chronic condition among children. Novel, safe, and reliable treatment strategies are the focus of current research on pediatric asthma. Amygdalin, mainly present in bitter almonds, has anti-inflammatory and immunoregulatory potential, but its effect on asthma remains uninvestigated. Here, the impact of amygdalin on the thymic stromal lymphopoietin (TSLP)-dendritic cell (DC)-OX40L axis was investigated. A BALB/c mouse model for allergic asthma was established using the ovalbumin-sensitization method. Amygdalin treatment was administered between days 21 and 27 of the protocol. Cell numbers and hematoxylin and eosin (H&E) staining in bronchoalveolar lavage fluid (BALF) were used to observe the impact of amygdalin on airway inflammation. TSLP, IL-4, IL-5, IL-13, and IFN-γ concentrations were determined via Enzyme-linked immunosorbent assay (ELISA). TSLP, GATA-3, and T-bet proteins were measured using western blotting. Cell-surface receptor expression on DCs (MHC II, CD80, and CD86) was assessed via flow cytometry. OX40L mRNA and protein levels were detected using western blotting and qRT-PCR, respectively. Amygdalin treatment attenuated airway inflammation decreased BALF TSLP levels, inhibited DC maturation, restrained TSLP-induced DC surface marker expression (MHCII, CD80, and CD86), and further decreased OX40L levels in activated DCs. This occurred together with decreased Th2 cytokine levels (IL-4, IL-5, and IL-13) and GATA3 expression, whereas Th1 cytokine (IFN-γ) levels and T-bet expression increased. Amygdalin thus regulates the Th1/Th2 balance through the TSLP-DC-OX40L axis to participate in inflammation development in the airways, providing a basis for potential allergic asthma treatments.

Keywords: Airway inflammation; Amygdalin; Asthma; Dendritic cells; OX40 ligand; Th1-Th2 balance; Thymic stromal lymphopoietin.

MeSH terms

  • Amygdalin* / metabolism
  • Amygdalin* / pharmacology
  • Amygdalin* / therapeutic use
  • Animals
  • Asthma* / metabolism
  • Child
  • Cytokines / metabolism
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Humans
  • Inflammation / metabolism
  • Interleukin-13 / metabolism
  • Interleukin-13 / pharmacology
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Interleukin-5 / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • OX40 Ligand / metabolism
  • OX40 Ligand / pharmacology
  • Th2 Cells / metabolism
  • Thymic Stromal Lymphopoietin

Substances

  • Thymic Stromal Lymphopoietin
  • Interleukin-13
  • Amygdalin
  • OX40 Ligand
  • Interleukin-4
  • Interleukin-5
  • Cytokines