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An evaluation of the molecular mode of action of trans-resveratrol in the Porphyromonas gingivalis lipopolysaccharide challenged neuronal cell model.

Authors
  • Bahar, Bojlul1
  • Singhrao, Sim K2
  • 1 International Institute of Nutritional Sciences and Food Safety Studies, School of Sport and Health Sciences, University of Central Lancashire, Preston, PR1 2HE, Lancashire, UK. [email protected]
  • 2 Brain and Behavior Centre, Faculty of Clinical and Biomedical Sciences, School of Dentistry, University of Central Lancashire, Preston, UK.
Type
Published Article
Journal
Molecular Biology Reports
Publisher
Springer-Verlag
Publication Date
Dec 08, 2020
Identifiers
DOI: 10.1007/s11033-020-06024-y
PMID: 33289908
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Porphyromonas gingivalis triggers a range of innate immune responses in the host that may contribute to the development of periodontitis and dementing diseases including Alzheimer's disease (AD). This study aimed to assess the mode of action of trans-resveratrol in modulating the P. gingivalis lipopolysaccharide (PgLPS) induced metabolic inflammation in a neuronal cell model. Confluent IMR-32 neuroblastoma cells were treated with trans-resveratrol from Polygonum cuspidatum in the presence or absence of PgLPS. The abundance of messenger ribo-nucleic acid (mRNA) transcripts of a panel of 92 genes was quantitatively assessed through targeted transcriptome profiling technique and the biochemical pathways affected were identified through Ingenuity Pathway Analysis. Gene expression analysis revealed that trans-resveratrol down-regulated the mRNA of multiple gene markers including growth factors, transcription factors, kinases, trans-membrane receptors, cytokines and enzymes that were otherwise activated by PgLPS treatment of IMR-32 neuroblastoma cells. Pathway analysis demonstrated that the cellular oxidative stress caused by the activation of phosphoinositide-3-kinase/Akt1 (PI3K/Akt1) pathway that leads to the production of reactive oxygen species (ROS), chronic inflammatory response induced by the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway and nutrient utilization pathways were favourably modulated by trans-resveratrol in the PgLPS challenged IMR-32 cells. This study demonstrates the potential of trans-resveratrol as a bioactive compound with multiple modes of intracellular action further supporting its therapeutic application in neuroinflammatory diseases.

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