Identification of the biochemical mechanisms involved in the health benefits of plant (poly)phenols

C. G. FRAGA

Kobe

Congreso; 9th International Conference on Polyphenols and Health; 2019

ICPH

It is increasingly accepted that in mammals, the bioactivities of (poly)phenols (as parent compounds or as metabolites) can be mostly ascribed to their chemical and physical interactions with proteins and lipids. This understanding is physiologically relevant at the amounts of (poly)phenols and/or their metabolites present in mammalian organs and tissues, and contrast with unspecific chemical reactions by (poly)phenols, e.g. free radical scavenging and metal chelation, that barely can occur at a significant extent in vivo. As a paradigm of (poly)phenols, we have extensively characterized EC and EC-related compounds (ECrc = derivatives and metabolites) by their capacity to modulate cell redox signaling through extra- and intracellular actions, and by redox and non-redox mechanisms. Therefore, interacting from the outer layer of cell membranes, ECm can alter lipid rafts domains?, receptors (TLR-4), and functional proteins/enzymes (NADPH-oxidases). These interactions would be relevant for cells present in certain tissues that are exposed to ECrc, for example, the intestine and the vascular system. Once incorporated into the cells, ECrc can interact with: i) proteins and enzymes that define oxidant levels, e.g. enzymes that generate and/or metabolize superoxide, hydrogen peroxide and nitric oxide; ii) transcription factors especially those redox sensitive; and iii) oxidant species. Meanwhile, i) and ii) can be relevant in any tissue exposed to ECrc, the scavenging of oxidants will be relevant only in the upper digestive tract, in which the concentration of ECrc is high especially after the consumption of a EC-rich food. Accepting the ability of EC to regulate redox signaling as a relevant mechanism explaining its bioactivity, still remain open many question, e.g.: i) all the plant (poly)phenols can exert similar and/or equivalent changes; ii) if not, which other (poly)phenols can have similar actions in vivo; iii) which other mechanisms can be modified by EC and/or other compounds that can impact health; and iv) how the amount ingested can be optimized to reach the benefits. It can be concluded, that only understanding of the molecular mechanisms involved in biological actions of (poly)phenols we will be able to define recommendations in terms of which plants can better promote health, and/or the amounts necessary to provide health effects.Support: UBACyT 20020160100132BA (CGF), and PIP-CONICET 11220170100585CO.Keywords: flavonoids-superoxide-nitric oxide-transcription factors