Inhibitory Effect of Chebulic Acid on Alveolar Epithelial to Mesenchymal Transition in Response to Urban Particulate Matter Using Co-treatment and Post-treatment Exposure

Biol Pharm Bull. 2019;42(8):1322-1331. doi: 10.1248/bpb.b19-00061.

Abstract

Urban particulate matter (UPM) is atmospheric particulate samples obtained from industrialized urban areas. It is known that pulmonary fibrosis can result directly or indirectly from particulate matter. In this study, the protective effect of chebulic acid (CA) against UPM-induced epithelial-mesenchymal transition (EMT) in the pulmonary alveolar epithelial (PAE) cells were investigated. Our findings revealed that PAE cells were changed from the epithelial phenotype to mesenchymal one after exposure to UPM. Furthermore, co-treatment and post-treatment of CA inhibited EMT progression. Especially the key epithelial marker, E-cadherin, was down-regulated by UPM and recovered by CA. Also, gelatin zymogram showed that the activity of matrix metalloproteinase (MMP)-2 and MMP-9 was decreased by co-treatment and post-treatment of CA. Further investigation revealed that CA attenuated UPM-stimulated PAE cells invasion ability. These data showed that UPM promoted PAE cells invasion, reactive oxygen species-mediated extracellular matrix degradation and CA reduced the potential health risks associated with UPM.

Keywords: chebulic acid; epithelial–mesenchymal transition; lung fibrosis; urban particulate matter.

MeSH terms

  • Air Pollutants / toxicity*
  • Benzopyrans / pharmacology*
  • Cell Line
  • Cell Movement / drug effects
  • Epithelial Cells / drug effects*
  • Epithelial Cells / physiology
  • Epithelial-Mesenchymal Transition / drug effects*
  • Humans
  • Particulate Matter / toxicity*
  • Protective Agents / pharmacology*
  • Pulmonary Alveoli
  • Reactive Oxygen Species / metabolism

Substances

  • Air Pollutants
  • Benzopyrans
  • Particulate Matter
  • Protective Agents
  • Reactive Oxygen Species
  • chebulic acid