Tectorigenin inhibits oxidative stress by activating the Keap1/Nrf2/HO-1 signaling pathway in Th2-mediated allergic asthmatic mice

Free Radic Biol Med. 2024 Feb 20:212:207-219. doi: 10.1016/j.freeradbiomed.2023.12.031. Epub 2023 Dec 24.

Abstract

Asthma is a chronic obstructive airway condition and one of the most common non-communicable illnesses worldwide. Tectorigenin (Tec) is an isoflavonoid found in plants that possesses significant antioxidative and anti-inflammatory abilities. Nevertheless, the antioxidative properties of Tec have not yet been documented in allergic asthma. In this study, we created an asthmatic BALB/c mouse model induced by ovalbumin (OVA) and used it to assess the efficacy of Tec as a possible therapy agent. Tec decreased the serum OVA-specific immunoglobulin (Ig) E and IgG1 secretion levels. The total number of cells and the distribution of inflammatory cells decreased significantly in bronchoalveolar lavage fluid (BALF), with weakened inflammatory reaction in pulmonary tissues. Additionally, Tec regulated the T helper 1(Th1)/Th2 balance by increasing the expression of Th1- related factors (interleukin (IL)-12 and T-bet) and decreasing the expression of Th2-related factors (IL-4, IL-5, IL-13, and GATA binding protein 3. In addition, the pro-inflammatory cytokines such as IL-6, tumor necrosis factor-alpha, and IL-1β were also inhibited by Tec. Tec also dramatically increased antioxidant (catalase and superoxide dismutase) concentrations while lowering the intensity of the indicators of oxidative stress such as reactive oxygen species and malondialdehyde in BALF. Finally, Tec effectively activated the Keap1/Nrf2/HO-1 signaling pathway and prevented the epithelial-mesenchymal transition. The results of the current study show that Tec may be useful in relieving the inflammatory and oxidative stress responses associated with asthma.

Keywords: Asthma; Keap1/Nrf2/HO-1 pathway; Oxidative stress; Tectorigenin; Th2 response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma* / drug therapy
  • Asthma* / metabolism
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cytokines / metabolism
  • Disease Models, Animal
  • Immunoglobulin E
  • Isoflavones*
  • Kelch-Like ECH-Associated Protein 1 / genetics
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Lung / metabolism
  • Mice
  • Mice, Inbred BALB C
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • Ovalbumin
  • Oxidative Stress
  • Signal Transduction

Substances

  • tectorigenin
  • NF-E2-Related Factor 2
  • Kelch-Like ECH-Associated Protein 1
  • Immunoglobulin E
  • Cytokines
  • Ovalbumin
  • Keap1 protein, mouse
  • Isoflavones