title: Grape seed proanthocyanidin extract inhibits glutamate-induced cell death through inhibition of calcium signals and nitric oxide formation in cultured rat hippocampal neurons.
abstract: BACKGROUND
  Proanthocyanidin is a polyphenolic bioflavonoid with known antioxidant activity. Some flavonoids have a modulatory effect on [Ca²⁺]i. Although proanthocyanidin extract from blueberries reportedly affects Ca²⁺ buffering capacity, there are no reports on the effects of proanthocyanidin on glutamate-induced [Ca²⁺]i or cell death. In the present study, the effects of grape seed proanthocyanidin extract (GSPE) on glutamate-induced excitotoxicity was investigated through calcium signals and nitric oxide (NO) in cultured rat hippocampal neurons.
  
  
  RESULTS
  Pretreatment with GSPE (0.3-10 μg/ml) for 5 min inhibited the [Ca²⁺]i increase normally induced by treatment with glutamate (100 μM) for 1 min, in a concentration-dependent manner. Pretreatment with GSPE (6 μg/ml) for 5 min significantly decreased the [Ca²⁺]i increase normally induced by two ionotropic glutamate receptor agonists, N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). GSPE further decreased AMPA-induced response in the presence of 1 μM nimodipine. However, GSPE did not affect the 50 mM K+-induced increase in [Ca²⁺]i. GSPE significantly decreased the metabotropic glutamate receptor agonist (RS)-3,5-Dihydroxyphenylglycine-induced increase in [Ca²⁺]i, but it did not affect caffeine-induced response. GSPE (0.3-6 μg/ml) significantly inhibited synaptically induced [Ca²⁺]i spikes by 0.1 mM [Mg²⁺]o. In addition, pretreatment with GSPE (6 μg/ml) for 5 min inhibited 0.1 mM [Mg²⁺]o- and glutamate-induced formation of NO. Treatment with GSPE (6 μg/ml) significantly inhibited 0.1 mM [Mg²⁺]o- and oxygen glucose deprivation-induced neuronal cell death.
  
  
  CONCLUSIONS
  All these data suggest that GSPE inhibits 0.1 mM [Mg²⁺]o- and oxygen glucose deprivation-induced neurotoxicity through inhibition of calcium signals and NO formation in cultured rat hippocampal neurons.
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea.
authors.forename: Seo-Hee
authors.initials: SH
authors.lastname: Ahn
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Imju
authors.initials: I
authors.lastname: Jeong
authors.forename: Yi Jae
authors.initials: YJ
authors.lastname: Hong
authors.forename: Myung-Jun
authors.initials: MJ
authors.lastname: Kim
authors.forename: Duck-Joo
authors.initials: DJ
authors.lastname: Rhie
authors.forename: Yang-Hyeok
authors.initials: YH
authors.lastname: Jo
authors.forename: Sang June
authors.initials: SJ
authors.lastname: Hahn
authors.forename: Shin Hee
authors.initials: SH
authors.lastname: Yoon
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D020013:Calcium Signaling / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005971:Glutamates / Q000494:pharmacology*; D056604:Grape Seed Extract / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D044945:Proanthocyanidins / Q000627:therapeutic use*; D051381:Rats
chemical_list: D000975:Antioxidants; D005971:Glutamates; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins; D009569:Nitric Oxide