Neuroprotective effects of hesperetin in mouse primary neurones are independent of CREB activation
- 作者：Stephanie Rainey-Smith ; Lars-Wilhelm Schroetke ; Parmvir Bahia ; Ahmed Fahmi ; Rachel Skilton ; Jeremy P.E. Spencer ; Catherine Rice-Evans ; Marcus Rattray ; Robert J. Williams
- 关键词：Flavonoid ; Neurodegeneration ; MAP kinase ; Luciferase reporter
- 刊名：Neuroscience Letters
- 出版年：2008
- 期刊代码：52_03043940
- 类别：neu
- 出版时间：13 June 2008
- 卷：438
- 期：1
- 页码：29-33
- 文件大小：369 K
摘要
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.