a1 Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG2 6AP, UK
Emerging evidence suggests that dietary phytochemicals, in particular flavonoids, may exert beneficial effects on the central nervous system by protecting neurons against stress-induced injury, by suppressing neuroinflammation and by improving cognitive function. It is likely that flavonoids exert such effects, through selective actions on different components of a number of protein kinase and lipid kinase signalling cascades, such as the phosphatidylinositol-3 kinase (PI3K)/Akt, protein kinase C and mitogen-activated protein kinase (MAPK) pathways. This review explores the potential inhibitory or stimulatory actions of flavonoids within these pathways, and describes how such interactions are likely to underlie neurological effects through their ability to affect the activation state of target molecules and/or by modulating gene expression. Future research directions are outlined in relation to the precise site(s) of action of flavonoids within signalling pathways and the sequence of events that allow them to regulate neuronal function.
Abbreviations: MAPK, mitogen-activated protein kinase; ERK, extracellular signal-regulated protein kinase; JNK, c-Jun N-terminal kinase; PI3K, phosphatidylinositol-3 kinase; PKB, protein kinase B; PKC, protein kinase C; ASK1, apoptosis signal-regulating kinase 1; STAT-1, signal transducer and activator of transcription-1; AP-1, activated protein-1; CREB, cAMP response element-binding protein; ATF-1/2, activating transcription factor 1/2; MSK1, mitogen- and stress-activated protein kinase 1; mTOR, mammalian target of rapamycin; p47phox, NADPH oxidase (p47 cytoplasmic element; p90RSK (RSK), 90 kDa ribosomal S6 kinase; MEF-2, myocyte enhancer factor 2; DSP, dual specificity phosphatase; PTEN, phosphatase and tensin homologue deleted on chromosome ten; LPS, lipopolysacharide; IL-1β, interleukin-1β; iNOS, inducible nitric oxide synthase; eNOS, endothelial nitric oxide synthase; IFN-γ, interferon gamma; LDL, low-density lipoprotein; NO∙, nitric oxide; TNF-α, tumour necrosis factor-alpha; BBB, blood–brain barrier; CNS, central nervous system