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

• Published in: Cellular and molecular neurobiology 2009-12, Vol.29 (8), p.1121-1129
• Main Authors: Fujishita, Kayoko, Ozawa, Tetsuro, Shibata, Keisuke, Tanabe, Shihori, Sato, Yoji, Hisamoto, Masashi, Okuda, Tohru, Koizumi, Schuichi
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes - cytology; Astrocytes - drug effects; Astrocytes - metabolism; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Death - drug effects; Cytoprotection - drug effects; Gene Expression Profiling; Grape Seed Extract - pharmacology; Hydrogen Peroxide - pharmacology; Interleukin-6 - genetics; Interleukin-6 - metabolism; Neurobiology; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Neuroprotective Agents - pharmacology; Neurosciences; Original Paper; Oxidative Stress - drug effects; Rats; Rats, Wistar; RNA, Messenger - genetics; RNA, Messenger - metabolism; Subcellular Fractions - drug effects; Subcellular Fractions - metabolism; Time Factors; Up-Regulation - drug effects; Up-Regulation - genetics; Vitaceae; Vitis vinifera
• ISSN: 0272-4340; 1573-6830; 1573-6830
• 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 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.