Suppressive Effects of Rosmarinic Acid Rich Fraction from Perilla on Oxidative Stress, Inflammation and Metastasis Ability in A549 Cells Exposed to PM via C-Jun, P-65-Nf-Κb and Akt Signaling Pathways

Biomolecules. 2021 Jul 23;11(8):1090. doi: 10.3390/biom11081090.

Abstract

Particulate matter from forest fires (PMFF) is an environmental pollutant causing oxidative stress, inflammation, and cancer cell metastasis due to the presence of polycyclic aromatic hydrocarbons (PAHs). Perilla seed meal contains high levels of polyphenols, including rosmarinic acid (RA). The aim of this study is to determine the anti-oxidative stress, anti-inflammation, and anti-metastasis actions of rosmarinic acid rich fraction (RA-RF) from perilla seed meal and its underlying molecular mechanisms in A549 cells exposed to PMFF. PMFF samples were collected via the air sampler at the University of Phayao, Thailand, and their PAH content were analyzed using GC-MS. Fifteen PAH compounds were detected in PMFF. The PMFF significantly induced intracellular reactive oxygen species (ROS) production, the mRNA expression of pro-inflammatory cytokines, MMP-9 activity, invasion, migration, the overexpression of c-Jun and p-65-NF-κB, and Akt phosphorylation. Additionally, the RA-RF significantly reduced ROS production, IL-6, IL-8, TNF-α, and COX-2. RA-RF could also suppress MMP-9 activity, migration, invasion, and the phosphorylation activity of c-Jun, p-65-NF-κB, and Akt. Our findings revealed that RA-RF has antioxidant, anti-inflammatory, and anti-metastasis properties via c-Jun, p-65-NF-κB, and Akt signaling pathways. RA-RF may be further developed as an inhalation agent for the prevention of lung inflammation and cancer metastasis induced by PM exposure.

Keywords: inflammation; metastasis; particulate matter; perilla; reactive oxygen species; rosmarinic acid rich fraction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants
  • Apoptosis
  • Cell Movement
  • Cell Survival
  • Cinnamates / pharmacology*
  • Cytokines / metabolism
  • Depsides / pharmacology*
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Inflammation*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis*
  • Oxidative Stress*
  • Particulate Matter
  • Perilla / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • Reactive Oxygen Species
  • Rosmarinic Acid
  • Transcription Factor RelA / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cinnamates
  • Cytokines
  • Depsides
  • Particulate Matter
  • Proto-Oncogene Proteins c-jun
  • Reactive Oxygen Species
  • Transcription Factor RelA
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt