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Neuroprotective effects of hesperetin in mouse primary neurones are independent of CREB activation

Rainey-Smith, S., Schroetke, L.W., Bahia, P., Fahmi, A., Skilton, R., Spencer, J.P.E. ORCID:, Rice-Evans, C., Rattray, M. and Williams, R.J. (2008) Neuroprotective effects of hesperetin in mouse primary neurones are independent of CREB activation. Neuroscience Letters, 438 (1). pp. 29-33. ISSN 0304-3940

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To link to this item DOI: 10.1016/j.neulet.2008.04.056


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 (100-300 nM, 15 min) caused significant increases in the level of ERK1/2 phosphorylation, but did not increase CREB phosphorylation. Administration of hesperetin for 18 h did not alter gene expression driven by the cyclic AMP response element (CRE), assessed using a luciferase reporter system, but 300 nM 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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Item Type:Article
Divisions:Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Human Nutrition Research Group
Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
ID Code:13652
Uncontrolled Keywords:flavonoid, neurodegeneration, MAP kinase, luciferase reporter, GREEN TEA CATECHINS, CORTICAL-NEURONS, AGLYCONE HESPERETIN, C-JUN, FLAVONOIDS, QUERCETIN, KINASE, MEMORY, METABOLITES, NARINGENIN Animals Antioxidants/pharmacology/therapeutic use Brain/*drug effects/metabolism Cell Death/drug effects/physiology Cells, Cultured Cyclic AMP Response Element-Binding Protein/*drug effects/genetics/metabolism Dose-Response Relationship, Drug Enzyme Activation/drug effects/physiology Enzyme Inhibitors/pharmacology Extracellular Signal-Regulated MAP Kinases/drug effects/metabolism Flavonoids/pharmacology/therapeutic use Gene Expression Regulation/drug effects/genetics Hesperidin/*pharmacology/therapeutic use Humans Mice Neurodegenerative Diseases/*drug therapy/metabolism/physiopathology Neurons/*drug effects/metabolism Neuroprotective Agents/*pharmacology/therapeutic use Oxidative Stress/drug effects/physiology Phosphorylation/drug effects Transcriptional Activation/drug effects/genetics Tumor Cells, Cultured

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