Polyphenols, food and pharma. Current knowledge and directions for future research.

Polyphenols are a large family of phytochemicals with great chemical diversity, known to be bioactive compounds of foods, species, medicinal plants and nutraceuticals. These compounds are ingested through the diet in significant amounts, around 1 g per day, an amount that be may be increased through supplements. The in vitro action of many representative polyphenols has been reported. However, their beneficial effects and their role in modulating the risk of high-prevalence diseases are difficult to demonstrate due to the wide variability of polyphenol structures and bioactive actions; the complexity of estimating the polyphenol content of food as a result of their variability in foods and cooked dishes; the potential modulation of the effects of polyphenols by food matrices; the addition of polyphenols and their synergistic interactions with each other and with other dietary bioactive components; the modulation of polyphenol bioavailability as a consequence of food composition and culinary techniques; their metabolism by the human body and the polyphenol gut microbiota metabolism in each metabotypes. Computational strategies, including virtual screening, shape-similarity-screening and molecular docking, were recently used to identify potential targets of polyphenols and thus gain a better understanding of the therapeutic effects exerted of polyphenols and modify natural polyphenol structures to potentiate specific activities. Here, we present the most relevant current knowledge and propose directions for future research in these fields, from the culinary world to the clinical setting. We hope this commentary will prompt scientists and clinicians to consider the therapeutic value of bioactive polyphenols and help shed some light on how much scientific truth lies in Hippocrates' famous quote: "Let your food be your medicine".