The regulatory effect of flavonoids extracted from Abutilon theophrasti leaves on gene expression in LPS-induced ALI mice via the NF-κB and MAPK signaling pathways

Pharm Biol. 2019 Dec;57(1):514-518. doi: 10.1080/13880209.2019.1648523.

Abstract

Context: ALI is a common disease characterized by acute pulmonary inflammatory disorder. Abutilon theophrasti Medik. (Malvaceae), as a Chinese traditional medicine, is used for the treatment of inflammation. Its main constituents are flavonoid compounds. Objective: This study investigates the regulatory effect of a TFE from Abutilon theophrasti leaves on gene expression in LPS-induced ALI mice via the NF-κB and MAPK signaling pathways. Materials and methods: Kunming mice were intragastrically administered TFE (0.25, 0.5, 1.0 g/kg) for 5 days, and then ALI was induced via intranasal administration 40 μg of LPS in 10 μL PBS after intragastric administration on the 5th day, and PBS and DEX (2 mg/kg) were negative and positive control groups, respectively. Results: The relative expression of iNOS gene was 0.707, 0.507 and 0.483 for 0.25, 0.5 and 1.0 g/kg TFE, and COX-2 gene expression was also reduced after treatment by three concentrations of TFE with 0.768, 0.545, and 0.478. The mRNA expression levels of p65 were 0.61, 0.43 and 0.27 for 0.25, 0.5 and 1.0 g/kg TFE and IκB levels were increased in a dose-dependent manner with 3.99, 13.69 and 34.36. 0.5 and 1.0 g/kg TFE inhibited the expression of ERK1/2 with 0.59 and 0.38, p38MAPK with 0.62 and 0.54, and JNK with 0.37 and 0.29, and JNK mRNA expression was 0.60 for 0.25 g/kg TFE. Discussion and conclusion: These results indicate that the regulatory mechanisms of TFE on gene expression in LPS-induced ALI mice include inhibition of the NF-κB and MAPK signaling pathways.

Keywords: Anti-inflammatory effect; quantitative real-time PCR; regulatory mechanism; total flavonoid extract.

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Animals
  • Cyclooxygenase 2 / metabolism
  • Drugs, Chinese Herbal / pharmacology
  • Flavonoids / pharmacology*
  • Gene Expression / drug effects
  • I-kappa B Kinase / metabolism
  • Inflammation / drug therapy
  • Lipopolysaccharides
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Malvaceae
  • Mice
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase / drug effects
  • Nitric Oxide Synthase / metabolism
  • Plant Leaves
  • Transcription Factor RelA / metabolism

Substances

  • Drugs, Chinese Herbal
  • Flavonoids
  • Lipopolysaccharides
  • NF-kappa B
  • Rela protein, mouse
  • Transcription Factor RelA
  • Nitric Oxide Synthase
  • Cyclooxygenase 2
  • I-kappa B Kinase

Grants and funding

The authors are grateful for the financial support from the Natural Science Foundation of Liaoning Province of China [Grant No.20180550647] and Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education.