Grape seed extract acting on astrocytes reveals neuronal protection against oxidative stress via interleukin-6-mediated mechanisms

Cell Mol Neurobiol. 2009 Dec;29(8):1121-9. doi: 10.1007/s10571-009-9403-5.


Grape polyphenols are known to protect neurons against oxidative stress. We used grape seed extract (GSE) from "Koshu" grapes (Vitis vinifera) containing a variety of polyphenols, and performed transcriptome analysis to determine the effects of GSE on primary cultures of astrocytes in the hippocampus. GSE upregulated various mRNAs for cytokines, among which interleukin-6 (IL-6) showed the biggest increase after treatment with GSE. The GSE-evoked increase in IL-6 mRNAs was confirmed by quantitative RT-PCR. We also detected IL-6 proteins by ELISA in the supernatant of GSE-treated astrocytes. We made an oxidative stress-induced neuronal cell death model in vitro using a neuron rich culture of the hippocampus. Treatment of the neurons with H(2)O(2) caused neuronal cell death in a time- and concentration-dependent manner. Exogenously applied IL-6 protected against the H(2)O(2)-induced neuronal cell death, which was mimicked by endogenous IL-6 produced by GSE-treated astrocytes. Taken together, GSE acting on astrocytes increased IL-6 production, which functions as a neuroprotective paracrine, could protect neuronal cells from death by oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology*
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Cell Death / drug effects
  • Cytoprotection / drug effects*
  • Gene Expression Profiling
  • Grape Seed Extract / pharmacology*
  • Hydrogen Peroxide / pharmacology
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism
  • Neurons / cytology*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Subcellular Fractions / drug effects
  • Subcellular Fractions / metabolism
  • Time Factors
  • Up-Regulation / drug effects
  • Up-Regulation / genetics


  • Grape Seed Extract
  • Interleukin-6
  • Neuroprotective Agents
  • RNA, Messenger
  • Hydrogen Peroxide