Abstract
Dietary flavonoids, including the citrus flavanone hesperetin, may have stimulatory effects on cytoprotective intracellular signalling pathways. In primary mouse cortical neurone cultures, but not SH-SY5Y human neuroblastoma cells or human primary dermal fibroblasts (Promocells), hesperetin (100-300nM, 15min) caused significant increases in the level of ERK1/2 phosphorylation, but did not increase CREB phosphorylation. Administration of hesperetin for 18h did not alter gene expression driven by the cyclic AMP response element (CRE), assessed using a luciferase reporter system, but 300nM hesperetin partially reversed staurosporine-induced cell death in primary neurones. Our data show that hesperetin is a neuroprotective compound at concentrations where antioxidant effects are unlikely to predominate. The effects of hesperetin are cell-type dependent and, unlike the flavanol (-)epicatechin, neuroprotection in vitro is not associated with enhanced CREB phosphorylation or CRE-mediated gene expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antioxidants / pharmacology
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Antioxidants / therapeutic use
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Brain / drug effects*
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Brain / metabolism
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Cell Death / drug effects
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Cell Death / physiology
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Cells, Cultured
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Cyclic AMP Response Element-Binding Protein / drug effects*
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Cyclic AMP Response Element-Binding Protein / genetics
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Cyclic AMP Response Element-Binding Protein / metabolism
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Dose-Response Relationship, Drug
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Enzyme Activation / drug effects
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Enzyme Activation / physiology
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Enzyme Inhibitors / pharmacology
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Extracellular Signal-Regulated MAP Kinases / drug effects
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Flavonoids / pharmacology
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Flavonoids / therapeutic use
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics
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Hesperidin / pharmacology*
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Hesperidin / therapeutic use
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Humans
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Mice
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Neurodegenerative Diseases / drug therapy*
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Neurodegenerative Diseases / metabolism
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Neurodegenerative Diseases / physiopathology
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Neurons / drug effects*
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Neurons / metabolism
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Neuroprotective Agents / pharmacology*
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Neuroprotective Agents / therapeutic use
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Oxidative Stress / drug effects
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Oxidative Stress / physiology
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Phosphorylation / drug effects
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Transcriptional Activation / drug effects
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Transcriptional Activation / genetics
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Tumor Cells, Cultured
Substances
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Antioxidants
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Creb1 protein, mouse
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Cyclic AMP Response Element-Binding Protein
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Enzyme Inhibitors
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Flavonoids
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Neuroprotective Agents
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Hesperidin
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Extracellular Signal-Regulated MAP Kinases
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hesperetin