Abstract
Glutamate excitotoxicity is mediated by intracellular Ca(2+) overload, caspase-3 activation, and ROS generation. Here, we show that curcumin, tannic acid (TA) and (+)-catechin hydrate (CA) all inhibited glutamate-induced excitotoxicity. Curcumin inhibited PKC activity, and subsequent phosphorylation of NR1 of the NMDA receptor. As a result, glutamate-mediated Ca(2+) influx was reduced. TA attenuated glutamate-mediated Ca(2+) influx only when simultaneously administered, directly interfering with Ca(2+). Both curcumin and TA inhibited glutamate-induced caspase-3 activation. Although Ca(2+) influx was not attenuated by CA, caspase-3 was reduced by direct inhibition of the enzyme. All polyphenols reduced glutamate-induced generation of ROS.
MeSH terms
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Animals
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Caspase 3 / metabolism
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Catechin / chemistry
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Catechin / pharmacology
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Cell Death / drug effects
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Cells, Cultured
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Curcumin / chemistry
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Curcumin / pharmacology
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Enzyme Activation / drug effects
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Flavonoids / chemistry
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Flavonoids / pharmacology*
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Glutamic Acid / toxicity
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Neurons / cytology*
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Neurons / drug effects*
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Neuroprotective Agents / chemistry
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Neuroprotective Agents / pharmacology*
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Neurotoxins / toxicity
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Phenols / chemistry
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Phenols / pharmacology*
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Phosphorylation / drug effects
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Polyphenols
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Protein Kinase C / metabolism
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Rats
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Reactive Oxygen Species / metabolism
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Receptors, N-Methyl-D-Aspartate / metabolism
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Tannins / chemistry
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Tannins / pharmacology
Substances
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Flavonoids
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NR1 NMDA receptor
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Neuroprotective Agents
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Neurotoxins
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Phenols
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Polyphenols
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Reactive Oxygen Species
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Receptors, N-Methyl-D-Aspartate
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Tannins
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Glutamic Acid
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Catechin
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Protein Kinase C
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Caspase 3
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Curcumin