Polyphenol-based nutraceuticals for the control of angiogenesis: Analysis of the critical issues for human use.

Angiogenesis, the formation of new blood-vessel, is crucial in the pathogenesis of several diseases, and thus represents a druggable target for the prevention and treatment of different disorders. It is nowadays well kwon how diet can control cancer development and progression, and how the use of certain diet components can prevent cancer development. Several studies, also from our lab, now indicate that natural plant products including nutraceuticals modulate tumor angiogenesis. In this review, it is reported how phytochemicals, comprising hydroxytyrosol, resveratrol, genistein, curcumin, and the green tea component epigallocatechin-3-gallate among the others, negatively regulate angiogenesis. A single plant-derived compound may affect both endothelial and tumor cells, with the common denominator of anti-inflammatory and radical scavenger activities. Beside these positive features, documented in cellular and animal models, a series of critical issues should be considered from a pharmacological point of view as: what is the best source of bioactive compounds: food and beverages, extracted phytocomplexes, isolated nutraceuticals or synthetic analogues? How is the bioavailability of the compounds of interest in relation to the above source? Is there any biological activity by circulating metabolic derivatives? What is the best formulation, administration route and posology? How safe are in humans? How strong and reliable are the clinical trials designed for their use alone or in combination with conventional chemotherapy? After a dissertation of these critical points, the conclusion can be drawn that novel and effective strategies should be optimized to improve their bioavailability and efficacy, considering their exploitation as chemopreventive and/or curative approaches.