The neuroprotective potential of flavonoids: a multiplicity of effects

Abstract

Flavonoids exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. These effects appear to be underpinned by two common processes. Firstly, they interact with critical protein and lipid kinase signalling cascades in the brain leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and synaptic plasticity. Secondly, they induce beneficial effects on the vascular system leading to changes in cerebrovascular blood flow capable of causing angiogenesis, neurogenesis and changes in neuronal morphology. Through these mechanisms, the consumption of flavonoid-rich foods throughout life holds the potential to limit neurodegeneration and to prevent or reverse age-dependent loses in cognitive performance. The intense interest in the development of drugs capable of enhancing brain function means that flavonoids may represent important precursor molecules in the quest to develop of a new generation of brain enhancing drugs.

Fig. 1

The structures of the main classes of flavonoids. The major differences between the individual groups reside in the hydroxylation pattern of the ring-structure, the degree of saturation of the C-ring and the substitution of in the 3-position: a general structure of flavonoids, b structure of flavonols and flavones, c structure of flavanols, also referred as flavan-3-ols, d structure of anthocyanidins, e structure of flavanones and flavanonols and f structure of isoflavones

Fig. 2

Involvement of neuroinflammation, endogenous neurotoxins and oxidative stress in dopaminergic neurodegeneration. Structures of the 5-S-cysteinyl-dopamine (5-S-Cys-DA) and the dihydrobenzothiazine-1 (DHBT-1) are shown

Fig. 3

Signalling pathways underlying neuronal survival and cognitive performance. Flavonoids activate ERK-CREB pathway and the PI3 kinase-mTOR cascade leading to changes in synaptic plasticity. They are also capable of influencing neurogenesis through the activation of PI3 kinase-Akt-eNOS