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

Stephanie Rainey-Smith, Lars-Wilhelm Schroetke, Parmvir Bahia, Ahmed Fahmi, Rachel Skilton, Jeremy P E Spencer, Catherine Rice-Evans, Marcus Rattray, Robert J Williams

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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.
Original languageEnglish
Pages (from-to)29-33
Number of pages5
JournalNeuroscience Letters
Issue number1
Publication statusPublished - 13 Jun 2008


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