ABSTRACT
Introduction 354
Potential Bioactive Forms of Flavonoids In Vivo 355
Metabolism in the GI Tract and Liver 356
Colonic Metabolism 356
Intracellular Metabolism 358
Modulation of Signaling Cascades by Flavonoids 359
MAP Kinase Signaling and Cell Function 360
Interactions of Flavonoids Within Signaling Pathways 361
Specific Actions of Flavanols 362
Specific Actions of Flavonols 365
Summary 367
References 367
Flavonoids have been proposed to act as beneficial agents in a multitude of
disease states, including cancer, cardiovascular disease, and neurodegenerative
disorders. The biological effect of these polyphenols will ultimately depend on
the cellular effects of their circulating metabolites, such as glucuronides and
O-methylated forms and on the extent to which they interact with and/or associate with cells, either by interactions at the membrane or their uptake into the
cytosol. Following uptake, flavonoids and their metabolites may affect cells in
a number of ways: (i) by regulating the intracellular redox status, (ii) by effecting
enzyme function, (iii) by interacting with mitochondria, and (iv) by specific inter-
actions within intracellular signaling cascades vital to cell function. This review
will summarize the current knowledge on the role of flavonoids as modulators of
cell signaling pathways, such as the MAP kinase pathway, which are vital in
determining neuronal survival, regeneration, development, and death.
