Preventive effect of ursolic acid derivative on particulate matter 2.5-induced chronic obstructive pulmonary disease involves suppression of lung inflammation

IUBMB Life. 2020 Apr;72(4):632-640. doi: 10.1002/iub.2201. Epub 2019 Dec 16.

Abstract

Respiratory diseases like chronic obstructive pulmonary disease (COPD) are associated with the presence of particulate matter 2.5 (PM2.5) in the air. In the present study, the effect of synthesized ursolic acid derivatives on mice model of PM2.5-induced COPD was investigated in vivo. The mice model of COPD was established by the administration of 25 μL of PM2.5 suspension through intranasal route daily for 1 week. The levels of oxidative stress markers and inflammatory cytokines like tumor necrosis factors-α and interleukin-6 in the mice bronchoalveolar fluids increased markedly on administration with PM2.5. However, treatment with ursolic acid derivative caused a significant suppression in PM2.5-induced increase in oxidative stress markers and inflammatory cytokines in dose-dependent manner. Hematoxylin and eosin staining showed excessive inflammatory cell infiltration in pulmonary tissues in mice with COPD. The inflammatory cell infiltration was inhibited on treatment of the mice with ursolic acid derivative. The ursolic acid derivative treatment increased level of superoxide dismutase in mice with COPD. The lung injury induced by PM2.5 in mice was also prevented on treatment with ursolic acid derivative. Thus, ursolic acid derivative inhibits pulmonary tissues damage in mice through suppression of inflammatory cytokine and oxidative enzymes. Therefore, ursolic acid derivative can be of therapeutic importance for treatment of PM2.5-induced COPD.

Keywords: anti-inflammatory; bronchitis; cell infiltration; chronic obstructive pulmonary disease; particulate matter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid
  • Cytokines / metabolism
  • Disease Models, Animal
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Particulate Matter / toxicity*
  • Pneumonia / chemically induced
  • Pneumonia / drug therapy
  • Pneumonia / pathology
  • Protective Agents / chemical synthesis
  • Protective Agents / chemistry
  • Protective Agents / pharmacology*
  • Pulmonary Disease, Chronic Obstructive / chemically induced*
  • Pulmonary Disease, Chronic Obstructive / prevention & control*
  • Triterpenes / chemistry*
  • Triterpenes / pharmacology
  • Ursolic Acid

Substances

  • Cytokines
  • Particulate Matter
  • Protective Agents
  • Triterpenes