Inula japonica ameliorated the inflammation and oxidative stress in LPS-induced acute lung injury through the MAPK/NF-κB and Keap1/Nrf2 signalling pathways

J Pharm Pharmacol. 2023 Feb 8;75(2):287-299. doi: 10.1093/jpp/rgac084.

Abstract

Objectives: To investigate the protective effect and underlying mechanism of Inula japonica (TEIJ) in the treatment of acute lung injury (ALI).

Methods: Protective effects of TEIJ in the inflammation and oxidative stress were studied in lipopolysaccharide (LPS)-induced ALI mice. Meanwhile, Western blot and real-time qPCR were carried out to investigate the underlying mechanism of TEIJ for ALI as well as immunohistochemistry.

Key findings: TEIJ significantly alleviated the course of ALI via suppressing the interstitial infiltrated inflammatory cells, the increase of inflammatory factors and the decrease of anti-oxidative factors. TEIJ inactivated the MAPK/NF-κB signalling pathway to suppress the transcription of its downstream target genes, such as TNF-α, IL-6, etc. Meanwhile, TEIJ activated the Keap1/Nrf2 signalling pathway to regulate expression levels of Nrf2 and its target proteins. The results of LC-QTOF-MS/MS indicated potential active constituents of I. japonica, terpenoids and flavonoids. Additionally, terpenoids and flavonoids synergistically alleviated LPS-induced ALI depending on MAPK/NF-κB and Keap1/Nrf2 signalling pathways.

Conclusion: I. japonica could be considered a potential agent to treat ALI via regulating the MAPK/NF-κB and Keap1/Nrf2 signalling pathways.

Keywords: Inula japonica; ALI; NF-κB; Nrf2; synergistic effect.

MeSH terms

  • Acute Lung Injury* / metabolism
  • Animals
  • Flavonoids / pharmacology
  • Inflammation / metabolism
  • Inula* / metabolism
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Lipopolysaccharides / pharmacology
  • Lung
  • Mice
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Oxidative Stress
  • Tandem Mass Spectrometry
  • Terpenes / pharmacology

Substances

  • Flavonoids
  • Keap1 protein, mouse
  • Kelch-Like ECH-Associated Protein 1
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Terpenes
  • Nfe2l2 protein, mouse