Eupatilin Suppresses OVA-Induced Asthma by Inhibiting NF-κB and MAPK and Activating Nrf2 Signaling Pathways in Mice

Int J Mol Sci. 2022 Jan 29;23(3):1582. doi: 10.3390/ijms23031582.

Abstract

To investigate the effect of eupatilin in asthma treatment, we evaluated its therapeutic effect and related signal transduction in OVA-induced asthmatic mice and LPS-stimulated RAW264.7 cells. The BALF was tested for changes in lung inflammatory cells. Th2 cytokines in the BALF and OVA-IgE in the serum were measured by ELISA. H&E and PAS staining were used to evaluate histopathological changes in mouse lungs. The key proteins NF-κB, MAPK, and Nrf2 in lung tissues were quantitatively analyzed by Western blotting. Finally, we evaluated the effect of eupatilin on cytokines and related protein expression in LPS-stimulated RAW 264.7 cells in vitro. In OVA-induced asthmatic mice, eupatilin reduced the numbers of inflammatory cells, especially neutrophils and eosinophils. Eupatilin also decreased the levels of IL-5, IL-13 in the BALF and OVA-IgE in the serum. Furthermore, eupatilin inhibited the activation of NF-κB and MAPK pathways and increased the expression of Nrf2 in OVA-induced asthmatic mice. In vitro, eupatilin significantly reduced LPS-stimulated NO, IL-6, and ROS production. Additionally, the NF-κB, MAPK, and Nrf2 protein expression in LPS-stimulated RAW264.7 cells was consistent with that in OVA-induced asthmatic lung tissues. In summary, eupatilin attenuated OVA-induced asthma by regulating NF-κB, MAPK, and Nrf2 signaling pathways. These results suggest the utility of eupatilin as an anti-inflammatory drug for asthma treatment.

Keywords: MAPK; NF-κB; Nrf2; asthma; eupatilin.

MeSH terms

  • Animals
  • Asthma / chemically induced
  • Asthma / drug therapy*
  • Asthma / immunology
  • Bronchoalveolar Lavage Fluid / immunology
  • Disease Models, Animal
  • Eosinophils / drug effects
  • Eosinophils / metabolism
  • Female
  • Flavonoids / administration & dosage*
  • Flavonoids / chemistry
  • Flavonoids / pharmacology
  • Gene Expression Regulation / drug effects
  • Lipopolysaccharides / adverse effects*
  • Lipopolysaccharides / immunology
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Molecular Structure
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism*
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Ovalbumin / adverse effects*
  • Ovalbumin / immunology
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism

Substances

  • Flavonoids
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, mouse
  • Reactive Oxygen Species
  • eupatilin
  • Ovalbumin