Broad spectrum effects of natural phytochemicals on disease prevention and wellbeing

Phytochemicals trigger cellular pathways leading to the prevention of pathological conditions associated with cancers, cardiovascular and neurodegenerative diseases. Although this positive association evidenced by interventional and observational studies is debated and subjected to criticism, biochemical and genetic studies on cellular and animal models on the mechanism(s) of action of phytochemicals provide a functional explanation of how and why a diet rich in fruits and vegetables can protect against degenerative diseases. The apparent contradiction existing between epidemiological observations and molecular studies on pre-clinical models generated, in our opinion, a shadow zone in the field cleverly exploited commercially by companies producing and distributing dietary supplements, nutraceuticals and functional foods. In fact, the market of food supplements is invaded by products enriched with bioactive compounds (largely polyphenols) claiming miraculous healthy effects against cancer and other degenerative diseases.
In the attempt to discriminate between facts and fancies regarding the capacity of phytochemicals to ameliorate pathological conditions, it is necessary to critically consider some key issues, such as low bioavailability and metabolism. As a consequence of these processes, circulating concentrations of phytochemicals and their metabolites are extremely low, suggesting that a regular diet, or a diet supplemented with phytochemical-enriched foods cannot provide adequate amounts (micromolar concentrations) of compounds compatible with any described chemopreventive effect. Therefore, when considering potential clinical applications of phytochemicals, it is important to differentiate between pharmacological (hundreds of milligrams in concentrated doses) and nutritional doses (a few milligrams diluted in the diet). In the latter case, low concentrations do not saturate metabolic pathways that rely on the supply of cofactors, such as UDP-glucuronic acid and circulating, and unconjugated molecules are not found in the blood. Only after the intake of large doses, which saturate conjugation enzymes, free aglycones can be detected in the plasma, usually for a short window of time. The drawback of the administration of pharmacological doses of phytochemical is, of course, the presence of cytotoxic effects.The experimental hypothesis on which we are intensively working regards the demonstration that the low bioavailability of phytochemicals favors (perhaps) the well-being, but represents an obstacle to their pharmacological application. In contrast, the pleiotropic functions of such compounds results in advantages when administered as drugs, since they can trigger multiple cellular targets.
This project will provide new career perspectives to the members of the research groupdeveloping expertise in managing independent research, gaining complementary skills (supervision, leadership, working in a team, exchange of knowledge) and therefore meet the requirements to qualify for academic position within CNR and Universities, or in the private sector. This innovative project meets the objectives of Horizon 2020 first societal challenge "Health, demographic change and wellbeing", aimed to amelioratetreatments of large-scale social diseases and improvehealthcare. Moreover, these activities respond to the increasing demands of industrial sector.
Finally, efforts will be made to propose measures for an adequate results dissemination to the large public (e.g., press release, web site, open-day to target teachers and high school students) and to the academic sector (e.g., seminars, peer-reviewed open access publications, conferences presentations).