Fig. (4).

Schematic representation of absorption, biotransformation and excretion of polyphenols in the human body. Along the digestive process, polyphenol-rich food suffers transformations, starting in the mouth, stomach and throughout the entire gastrointestinal tract. The gastrointestinal tract is covered by the mucosa, which functions as a physical barrier, determining bioavailability of xenobiotics like polyphenols. This function is mediated by physical walls, metabolism and passive (solid arrows)/active (dashed arrows) transport mechanisms. Absorption occurs mainly at the duodenum and the proximal half of jejunum, in enterocytes. Enterocytes apical cell membranes contain microvilli, which increase the surface area of absorption. Passive intestinal permeability occurs mainly for aglycones and simple phenolic acids. Absorption of glycosylated compounds is usually preceded by release of aglycone through hydrolysis by lactase phloridzin hydrolase (LPH). Free aglycone can then enter the epithelial cells by passive diffusion. Alternatively, glycosylated compounds enter epithelial cells by the active sodium-dependent glucose transporter SGLT1 and are hydrolyzed by the cytosolic β-glucosidase (CBG). Once inside enterocytes, polyphenols can be extruded into the lumen by efflux transporters (P-gp, MRPs, BCRP). Compounds not absorbed reach the colon where they can be extensively metabolized by microbiota. Several transformations in polyphenols structure can occur. Most of the colonic metabolites are excreted in feces, although absorption can still take place. Then, polyphenols can undergo phase I and phase II reactions. Phase I reactions include oxidative and reductive reactions. Glucuronidation, sulfation and methylation are the most frequent phase II reactions. The conjugates, being more water soluble, are rapidly excreted through bile or urine [84]. Metabolites can then be transported into the bile (enterohepatic recirculation) and secreted back to the duodenum. Degradation of metabolites in the intestine generates catabolites available for reabsorption.