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: https://orcid.org/0000-0003-2931-7274, 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 doi: 10.1016/j.neulet.2008.04.056

Abstract/Summary

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.