Pomegranate inhibits neuroinflammation and amyloidogenesis in IL-1β-stimulated SK-N-SH cells

Eur J Nutr. 2016 Jun;55(4):1653-60. doi: 10.1007/s00394-015-0984-0. Epub 2015 Jul 10.

Abstract

Purpose: Pomegranate fruit, Punica granatum L. (Punicaceae), and its constituents have been shown to inhibit inflammation. In this study, we aimed to assess the effects of freeze-dried pomegranate (PWE) on PGE2 production in IL-1β-stimulated SK-N-SH cells.

Methods: An enzyme immunoassay (EIA) was used to measure prostaglandin E2 (PGE2) production from supernatants of IL-1β-stimulated SK-N-SH cells. Expression of COX-2, phospho-IκB, and phospho-IKK proteins was evaluated, while NF-κB reporter gene assay was carried out in TNFα-stimulated HEK293 cells to determine the effect of PWE on NF-κB transactivation. Levels of BACE-1 and Aβ in SK-N-SH cells stimulated with IL-1β were measured with an in cell ELISA.

Results: PWE (25-200 μg/ml) dose dependently reduced COX-2-dependent PGE2 production in SK-N-SH cells stimulated with IL-1β. Phosphorylation of IκB and IKK was significantly (p < 0.001) inhibited by PWE (50-200 μg/ml). Our studies also show that PWE (50-200 μg/ml) significantly (p < 0.01) inhibited NF-κB transactivation in TNFα-stimulated HEK293 cells. Furthermore, PWE inhibited BACE-1 and Aβ expression in SK-N-SH cells treated with IL-1β.

Conclusions: Taken together, our study demonstrates that pomegranate inhibits inflammation, as well as amyloidogenesis in IL-1β-stimulated SK-N-SH cells. We propose that pomegranate is a potential nutritional strategy in slowing the progression of neurodegenerative disorders such as Alzheimer's disease.

Keywords: Amyloidogenesis; Interleukin-1β; Neuroinflammation; Neurons; Pomegranate.

MeSH terms

  • Amyloid / metabolism*
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors
  • Amyloid Precursor Protein Secretases / metabolism
  • Aspartic Acid Endopeptidases / antagonists & inhibitors
  • Aspartic Acid Endopeptidases / metabolism
  • Cell Line, Tumor
  • Cell Survival / physiology
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / metabolism
  • Freeze Drying
  • Fruit / chemistry
  • Gene Expression
  • Genes, Reporter
  • HEK293 Cells
  • Humans
  • I-kappa B Proteins / genetics
  • I-kappa B Proteins / metabolism
  • Inflammation / metabolism*
  • Interleukin-1beta / pharmacology
  • Lythraceae / chemistry*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neurons / cytology
  • Neurons / drug effects*
  • Phosphorylation
  • Plant Preparations / pharmacology*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Amyloid
  • I-kappa B Proteins
  • Interleukin-1beta
  • NF-kappa B
  • Plant Preparations
  • Tumor Necrosis Factor-alpha
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human
  • Dinoprostone