Various epidemiological investigations, as well as dietary supplementation studies in humans and animals, have established a positive correlation between the intake of flavonoid-rich foods or beverages and the attenuation or delayed onset of cardiovascular disease, cancer and neurodegeneration. Flavonoids are founds ubiquitously in the human diet, although some foods and beverages, such as tea, wine, cocoa, berries and citrus fruits are particularly rich sources of these plant phytochemicals. They are extensively metabolised at various sites within the human body, most notably the small intestine, large intestine and liver, where they are converted into a variety of metabolic forms. Due to this metabolism and the low extent of their overall absorption, it is likely that their beneficial actions are mediated by their abilities to interact with both protein and lipid kinase signalling cascades, rather than via their potential to act as classical antioxidants. The concentrations of flavonoids encountered in vivo are sufficiently high to exert pharmacological activity at receptors, and on kinases and transcription factors. Presently the precise sites of action are unknown, although it is likely that their activity depends on their ability to: 1) bind to ATP sites on enzymes and receptors; 2) modulate the activity of kinases directly, i.e. MAPKKK, MAPKK or MAPK; 3) affect the function of important phosphatases, which act in opposition to kinases; 4) preserve Ca2+ homeostasis, thereby preventing Ca2+-dependent activation of kinases in neurons; and 5) modulate signalling cascades lying downstream of kinases, i.e. transcription factor activation and binding to promoter sequences. Such interactions will be discussed in relation to the precise site(s) of action of flavonoids within signalling pathways and the sequence of events that allow them to regulate cellular function at various sites within the body.
|Title of host publication||Health benefits of organic food: effects of the environment|
|Editors||Ian Givens, Samantha Baxter, Anne Marie Minihane, Elizabeth Shaw|
|Number of pages||33|
|Publication status||Published - 2008|