title: Grape seed extract acting on astrocytes reveals neuronal protection against oxidative stress via interleukin-6-mediated mechanisms.
abstract: 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.
authors.affiliation: Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, 409-3898, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Fujishita
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ozawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shibata
authors.forename: Shihori
authors.initials: S
authors.lastname: Tanabe
authors.forename: Yoji
authors.initials: Y
authors.lastname: Sato
authors.forename: Masashi
authors.initials: M
authors.lastname: Hisamoto
authors.forename: Tohru
authors.initials: T
authors.lastname: Okuda
authors.forename: Schuichi
authors.initials: S
authors.lastname: Koizumi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D020869:Gene Expression Profiling; D056604:Grape Seed Extract / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D056604:Grape Seed Extract; D015850:Interleukin-6; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D006861:Hydrogen Peroxide