9E Health-Promoting Effects of Wine Phenolics 573
transporters such as SGLT-1 and then hydrolyzed by CBG, releasing the aglycone
(Ader et al. 2001; Henry-Vitrac et al. 2006; Nemeth et al. 2003; Shimizu et al. 2000).
Then, the aglycone can be further metabolized into conjugates, diffuse passively to
the circulation, or be excreted from the enterocyte back to the lumen through ATP-
binding cassette (ABC) transporters (Nemeth et al. 2003; Henry-Vitrac et al. 2006).
Very little is known about the absorption and metabolism of hydroxycinnamic and
hydroxybenzoic acids. Bioavailability studies from different sources suggest that
chlorogenic acid may be absorbed mainlyin the colon but also in the stomach after
hydrolysis by microbial esterases (Lafay et al. 2006; Nardini et al. 2002; Olthof
et al. 2003), while ferulic acid may be absorbed in the small intestine (Bourne
et al. 2000; Manach et al. 2005; Silberberg et al. 2006). Anthocyanins are reported to
be absorbed and eliminated very rapidly, and their bioavailability is very low (Frank
T et al. 2003; Bitsch et al. 2004; Manach etal. 2005). The stabilityof anthocyanins
in the gastrointestinal tract is variable and identification of their different metabo-
lites should be considered in order to evaluate the true degree of bioavailability
(Borges et al. 2007; Manach et al. 2005; McDougall et al. 2005). Most polyphenols
are excreted in urine and their metabolites exhibit different half-lives. Although the
human tissue distribution has recently been described (Henning et al. 2006), tissue
accumulation has not been yet demonstrated. However, plasma accumulation with
repeated ingestion is expected at least with metabolites exhibiting longer half-lives
(Manach et al. 2005).
9E.2 Antioxidant Properties and Vascular Effects
Reactive oxygen species (ROS) have been reported to act via different molecu-
lar pathways to play important roles in diverse pathological processes associated
with aging, including cardiovascular diseases, certain types of cancer, hypertension,
inflammation, neurological disorders, diabetes, and chronic kidney disease (Valko
et al. 2007). They are generated as a result of normal cell metabolism. However, dif-
ferent external agents (cytokines, toxins, drugs, radiation, etc.) can also trigger ROS
production. This can be largely counteracted by antioxidant defense systems, which
can be enzymatic (superoxide dismutase, catalase, glutathione peroxidase), non-
enzymatic (glutathione, paraoxonase), or dietary (antioxidant vitamins A, C, and
E, and polyphenols). Increased ROS levels may damage lipids, proteins, and DNA,
and can also trigger a stress signal that activates different redox-sensitive signaling
pathways that can have either damaging or potentially protective effects (Finkel
and Holbrook 2000). In general, it has been described that phenolic compounds are
secondary antioxidants included in the category of free radical terminators. Phenolic
antioxidants are excellent hydrogen or electron donors and their phenoxy radical
intermediates are relatively stable due to resonance delocalization of unpaired elec-
trons around the aromatic ring and lack of suitable sites for attack by molecular
oxygen (Shahidi et al. 1992). Consumption of red wine (Maxwell et al. 1994; Ser-
afini et al. 1998; Whitehead et al. 1995) and red grape juice (Castilla et al. 2006)