Cellular and Molecular Neurobiology

, Volume 29, Issue 8, pp 1121–1129 | Cite as

Grape Seed Extract Acting on Astrocytes Reveals Neuronal Protection Against Oxidative Stress via Interleukin-6-mediated Mechanisms

  • Kayoko Fujishita
  • Tetsuro Ozawa
  • Keisuke Shibata
  • Shihori Tanabe
  • Yoji Sato
  • Masashi Hisamoto
  • Tohru Okuda
  • Schuichi Koizumi
Original Paper


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 H2O2 caused neuronal cell death in a time- and concentration-dependent manner. Exogenously applied IL-6 protected against the H2O2-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.


Grape seed extract Astrocytes IL-6 Neuroprotection Oxidative stress 



We thank Dr. S. Maeda for critical reading and helpful support. This work was supported by a Univ. Yamanashi Grape polyphenols project from Ministry of Education, Culture, Sports, Science & Technology, a Grand-in-Aid for Scientific Research on Priority Area from Ministry of Education, Culture, Sports, Science & Technology, Japan (S.K. and K.F.), a Grand-in-Aid for Scientific Research (B) from JSPS (S.K. and K.F.), a Minamata disease project from Ministry of Environment of Japan (S.K.). S.K. was also supported by the Uragami Foundation and the Ono Foundation Japan.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Kayoko Fujishita
    • 1
  • Tetsuro Ozawa
    • 1
  • Keisuke Shibata
    • 1
  • Shihori Tanabe
    • 2
  • Yoji Sato
    • 2
  • Masashi Hisamoto
    • 3
  • Tohru Okuda
    • 3
  • Schuichi Koizumi
    • 1
  1. 1.Department of Pharmacology, Interdisciplinary Graduate School of Medicine and EngineeringUniversity of YamanashiYamanashiJapan
  2. 2.Division of Cellular and Gene Therapy ProductsNational Institute of Health SciencesTokyoJapan
  3. 3.The Institute of Enology and ViticultureUniversity of YamanashiYamanashiJapan

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