Tectorigenin inhibits inflammation and pulmonary fibrosis in allergic asthma model of ovalbumin-sensitized guinea pigs

J Pharm Pharmacol. 2020 Jul;72(7):956-968. doi: 10.1111/jphp.13271. Epub 2020 Apr 20.

Abstract

Objectives: The aim of this study was to evaluate the effect of tectorigenin on treating allergic asthma model of guinea pigs and investigate the underlying mechanisms.

Methods: Allergic asthma model of guinea pigs was established by sensitizing with ovalbumin (OVA). Then OVA-sensitized guinea pigs were injected with 10 mg/kg tectorigenin, 25 mg/kg tectorigenin or dexamethasone to investigate the effect of tectorigenin.

Key findings: High dose of tectorigenin effectively decreased the number of coughs, the number of inflammatory cells and the levels of pro-inflammatory factors. Moreover, tectorigenin could inhibit pulmonary fibrosis in guinea pigs sensitized with OVA. In addition, the functions of tectorigenin were realized through downregulating profibrotic factors of transforming growth factor (TGF)-β1, phosphorylated (p)-Smad2/3 and Smad4, upregulating fibrosis-inhibitor of Smad7 and decreasing pro-inflammatory factors of vascular endothelial growth factor A (VEGFA), tumour necrosis factor-α (TNF-α), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), p-inhibitor of nuclear factor-kappa B (NF-κB) kinase β (p-IKKβ) and NF-κB.

Conclusions: Tectorigenin could inhibit pulmonary fibrosis and airway inflammation through TGF-β1/Smad signalling pathway and TLR4/NF-κB signalling pathway. Therefore, tectorigenin might be a promising medicine to treat allergic asthma.

Keywords: allergic asthma; anti-inflammation; antifibrosis; tectorigenin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Asthma* / drug therapy
  • Asthma* / immunology
  • Disease Models, Animal
  • Drug Discovery
  • Guinea Pigs
  • Isoflavones / pharmacology*
  • NF-kappa B / immunology*
  • Pulmonary Fibrosis / drug therapy*
  • Signal Transduction / drug effects*
  • Smad Proteins
  • Toll-Like Receptor 4 / immunology*
  • Transforming Growth Factor beta1 / immunology*
  • Up-Regulation / drug effects
  • Up-Regulation / immunology

Substances

  • Anti-Inflammatory Agents
  • Isoflavones
  • NF-kappa B
  • Smad Proteins
  • Toll-Like Receptor 4
  • Transforming Growth Factor beta1
  • tectorigenin