The attenuating effects of 1,2,3,4,6 penta-O-galloyl-β-d-glucose on inflammatory cytokines release from activated BV-2 microglial cells

J Neuroimmunol. 2017 Apr 15:305:9-15. doi: 10.1016/j.jneuroim.2017.01.011. Epub 2017 Jan 18.

Abstract

Alzheimer's disease (AD) is the most common cause of neurodegeneration and dementia in the elderly. Dysregulated, chronic activation of microglia, the brain's resident macrophages, induces the release of excessive amounts of pro-inflammatory cytokines which has been implicated in the early stages of AD pathology. Therefore, suppressing the expression of these inflammatory mediators may decrease or delay the progression of AD. Many natural compounds derived from plants have shown anti-inflammatory activity. The naturally occurring 1,2,3,4,6 Penta-O-Galloyl-β-d-Glucose (PGG), is a polyphenolic compound highly enriched in Rhus chinensis Millplant. It is a potent anti-inflammatory agent that act through the inhibition of many cytokines in different experimental models. In the present study, we investigated the role of PGG as an anti-inflammatory agent in LPS/IFNγ activated BV-2 microglia cells. Mouse cytokine antibody arrays were used to assess the effect of PGG on the release of pro-inflammatory cytokines, and ELISA experiments were performed to validate the results from the arrays. The results obtained from the cytokine arrays, and ELISA assays showed that PGG decreased the expression of monocyte chemotactic protein-5 (MCP-5) 8-fold, and pro-matrix metalloproteinase 9 (Pro MMP-9) 10-fold. Both of these cytokines are upregulated during the inflammatory process and have been shown to be involved in brain injury, inflammation, and neurodegeneration. Therefore, these findings suggest that the anti-inflammatory effect of PGG on activated microglia involving the attenuation of MCP-5 and Pro MMP-9 cytokines.

Keywords: Alzheimer's disease; Matrix metalloproteinase-9; Monocyte chemotactic protein-5.

MeSH terms

  • Analysis of Variance
  • Animals
  • Cell Line, Transformed
  • Cell Survival / drug effects
  • Cytokines / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Hydrolyzable Tannins / pharmacology*
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / pharmacology
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Microglia / drug effects*
  • Microglia / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Protein Array Analysis

Substances

  • Cytokines
  • Hydrolyzable Tannins
  • Lipopolysaccharides
  • Nitric Oxide
  • pentagalloylglucose
  • Interferon-gamma
  • Nitric Oxide Synthase Type II
  • Matrix Metalloproteinase 9