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

• Published in: Neuroscience letters 2008-06, Vol.438 (1), p.29-33
• Main Authors: Rainey-Smith, Stephanie, Schroetke, Lars-Wilhelm, Bahia, Parmvir, Fahmi, Ahmed, Skilton, Rachel, Spencer, Jeremy P.E., Rice-Evans, Catherine, Rattray, Marcus, Williams, Robert J.
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Cell Death - drug effects; Cell Death - physiology; Cells, Cultured; Citrus; Cyclic AMP Response Element-Binding Protein - drug effects; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Enzyme Activation - physiology; Enzyme Inhibitors - pharmacology; Extracellular Signal-Regulated MAP Kinases - drug effects; Extracellular Signal-Regulated MAP Kinases - metabolism; Flavonoid; Flavonoids - pharmacology; Flavonoids - therapeutic use; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Hesperidin - pharmacology; Hesperidin - therapeutic use; Humans; Luciferase reporter; MAP kinase; Mice; Neurodegeneration; Neurodegenerative Diseases - drug therapy; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - physiopathology; Neurons - drug effects; Neurons - metabolism; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Oxidative Stress - drug effects; Oxidative Stress - physiology; Phosphorylation - drug effects; Transcriptional Activation - drug effects; Transcriptional Activation - genetics; Tumor Cells, Cultured; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• 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 (100–300nM, 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.