CONICET | Buscador de Institutos y Recursos Humanos

In mammals, the bioactivities of flavonoids (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 flavonoids and of their metabolites bioavailable in most organs and tissues, and contrast with unspecific chemical reactions, e.g. free radical scavenging and metal chelation that barely can occur at a significant extent in vivo. We have extensively characterized (-)-epicatechin (EC) and EC-related compounds (ECrc) by their capacity to modulate cell redox signaling through extra- and intracellular actions, and by redox and non-redox reactions. Therefore, interacting from the outer layer of cell membranes, ECrc can alter lipid rafts, bind to receptors (TLR4) and functional enzymes (NADPH oxidases) all of which regulates oxidant production. These interactions would be relevant for cells present in certain tissues that are exposed to ECrc, e.g. intestine and vasculature. Once incorporated into cells, ECrc can interact with: i) proteins and enzymes that define oxidant levels, mainly NADPH oxidases and NO synthases but also SOD, glutathione peroxidase and catalase; ii) transcription factors, especially those redox sensitive, e.g. NF-kB, nrf-2, PTP1-B; and iii) oxidant species, which is relevant in the gastrointestinal tract, in which ECrc can reach high concentrations. The actions of EC are consistent with the ones from other flavonoids, e.g. anthocyanins, in terms of regulating redox-pathways altered in pathological conditions many associated to obesity, e.g. hypertension, diabetes, renal dysfunction, and intestinal inflammation. The widespread observations of the antioxidant activity of flavonoids occurring in vivo, can be explained by the changes that are triggered by these phytochemicals in terms of regulation of redox signaling and its consequences. Support: UBACyT 20020160100132BA (CGF), and PIP-CONICET 11220170100585CO.