Apigenin attenuates inflammatory response in allergic rhinitis mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway

Environ Toxicol. 2023 Feb;38(2):253-265. doi: 10.1002/tox.23699. Epub 2022 Nov 9.

Abstract

Background: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated immune inflammatory response that mainly affects the nasal mucosa. Currently, there is evidence that apigenin, as a flavonoid, has anti-allergic potential.

Material/methods: In vitro, compound 48/80 and lipopolysaccharide (LPS) were used to induce mast cell activation and inflammation in HMC-1 cells. In vivo, ovalbumin (OVA) induced and stimulated AR in BALB/c mice. ELISA was used to detect the contents of β-hexosaminidase, histamine, eosinophil cationic protein (ECP), OVA-specific IgE, IgG1, and IgG2a, inflammatory factors in cells and mouse serum. Cell viability and apoptosis were measured with MTT and flow cytometry. Toll like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/Nuclear transcription factor-κB (NF-κB) pathway-related proteins in cells and mouse nasal mucosa tissues were analyzed with Western blotting. The levels of Th1 (IFN-γ) and Th2 (IL-4, IL-5, and IL-13) cytokines and Th1 (T-bet) and Th2 (GATA-3) specific transcription factors were also assessed. The ratio of Th1 (CD4+ IFN-γ+ ) / Th2 (CD4+ IL-4+ ) cells in mouse peripheral blood mononuclear cells was evaluated by flow cytometry.

Results: Apigenin significantly inhibited compound 48/80-induced secretion of β-hexosaminidase and histamine. Apigenin blocked LPS-induced decrease in cell viability and increase in cell apoptosis and inflammatory cytokine secretion by suppressing the activity of the TLR4/MyD88/NF-κB pathway. Apigenin treatment reduced the levels of OVA-specific IgE, IgG1 and IgG2a as well as β-hexosaminidase, histamine and ECP levels in mouse serum. Moreover, administration with apigenin decreased Th2 cytokine and transcription factor levels and increased Th1 cytokine and transcription factor levels, and promoted the ratio of Th1/Th2 cells in AR mice. Additionally, apigenin significantly alleviated nasal symptoms and nasal eosinophil infiltration in AR mice.

Conclusions: Apigenin alleviates the inflammatory response of allergic rhinitis by inhibiting the activity of the TLR4/MyD88/NF-κB signaling pathway.

Keywords: HMC-1 mast cells; TLR4/MyD88/NF-κB pathway; allergic rhinitis; apigenin; inflammatory response.

MeSH terms

  • Animals
  • Apigenin* / pharmacology
  • Apigenin* / therapeutic use
  • Cytokines / metabolism
  • Disease Models, Animal
  • Histamine / toxicity
  • Immunoglobulin E
  • Immunoglobulin G / metabolism
  • Immunoglobulin G / toxicity
  • Interleukin-4
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Myeloid Differentiation Factor 88* / metabolism
  • NF-kappa B* / metabolism
  • Ovalbumin / pharmacology
  • Rhinitis, Allergic* / chemically induced
  • Rhinitis, Allergic* / drug therapy
  • Signal Transduction
  • Th2 Cells
  • Toll-Like Receptor 4* / metabolism
  • beta-N-Acetylhexosaminidases / metabolism

Substances

  • Apigenin
  • beta-N-Acetylhexosaminidases
  • Cytokines
  • Histamine
  • Immunoglobulin E
  • Immunoglobulin G
  • Interleukin-4
  • Lipopolysaccharides
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Ovalbumin
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4