Arenaria kansuensis attenuates pulmonary fibrosis in mice via the activation of Nrf2 pathway and the inhibition of NF-kB/TGF-beta1/Smad2/3 pathway

Phytother Res. 2021 Feb;35(2):974-986. doi: 10.1002/ptr.6857. Epub 2020 Sep 30.

Abstract

Pulmonary fibrosis is a key feature of COVID-19, Chinese herbal medicine Arenaria kansuensis has been used for curing pulmonary disease and antivirus for a long time and it has the potential against COVID-19. In this work, protective effect of A. kansuensis ethanol extract (AE) on pulmonary fibrosis was evaluated through paraquat (PQ)-induced pulmonary fibrosis animal model. Results showed that AE could significantly improve the survival rate, increase the body weight and reduce the lung index of mice at the raw drug doses of 700 and 350 mg/kg. Histopathological observation results showed that the destruction degree of lung tissue structure in mice was significantly improved with the increase of AE dosage. Collagen deposition in lung interstitium was significantly reduced. The marker protein alpha-SMA involved in PF were significantly inhibited through repressing TGF-beta1/Smads pathway. The degree of inflammatory infiltration was significantly reduced and inflammatory cytokines were significantly inhibited in mice through inhibiting the NF-kB-p65. Besides, oxidant stress level including upregulated ROS and down-regulated SOD and GSH was efficiently improved by AE through upregulation of Nrf2 and downregulation of NOX4. In summary, this study firstly showed that the protective effect of AE on pulmonary fibrosis was partly due to activation of Nrf2 pathway and the inhibition of NF-kB/TGF-beta1/Smad2/3 pathway.

Keywords: Arenaria kansuensis; COVID-19; inflammation; oxidative stress; pulmonary fibrosis.

MeSH terms

  • Acute Lung Injury
  • Animals
  • Arenaria Plant / chemistry*
  • Arenaria Plant / physiology
  • COVID-19 / complications
  • COVID-19 / pathology
  • COVID-19 Drug Treatment
  • Cytokines / metabolism
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Ethanol / chemistry
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Paraquat
  • Phytotherapy
  • Pulmonary Edema / drug therapy
  • Pulmonary Edema / pathology
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / metabolism*
  • Pulmonary Fibrosis / pathology
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / physiology
  • Signal Transduction / drug effects
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Survival Rate
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Cytokines
  • Drugs, Chinese Herbal
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Smad2 Protein
  • Smad2 protein, mouse
  • Smad3 Protein
  • Smad3 protein, mouse
  • Transforming Growth Factor beta1
  • Ethanol
  • Paraquat

Supplementary concepts

  • Paraquat lung