Neuroprotective effects of hesperetin in mouse primary neurones are independent of CREB activation.
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.
Rainey-Smith
Stephanie
S
King's College London, The Wolfson Centre for Age-Related Diseases, Guy's Hospital Campus, London SE1 1UL, UK.
Schroetke
Lars-Wilhelm
LW
Bahia
Parmvir
P
Fahmi
Ahmed
A
Skilton
Rachel
R
Spencer
Jeremy P E
JP
Rice-Evans
Catherine
C
Rattray
Marcus
M
Williams
Robert J
RJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006569:Hesperidin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured
D000975:Antioxidants; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D005419:Flavonoids; D018696:Neuroprotective Agents; D006569:Hesperidin; D048049:Extracellular Signal-Regulated MAP Kinases; C013015:hesperetin