Background\r\nProanthocyanidin 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.\r\nResults\r\nPretreatment 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.\r\nConclusions\r\nAll 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.
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