Resveratrol metabolic pathways

Figure 14.5 Intestinal resveratrol metabolic pathway proposed after oral administration using Caco-2 monolayers. SULT and UGT enzymes shown in bold represent the predominant contribution to sulfate and glucuronide formation.

Zra -resveratrol-4 -0-sulfate (S2), and traras-resveratrol-3-O-sulfate (S3), respectively. Incubation in the presence of human recombinant sulfotransferases (SULTs) demonstrated that SI is almost exclusively catalyzed by SULT1A1 and only to a minor extent by SULT 1A2, 1A3, and 1E1, whereas S2 is selectively formed by SULT1E1. S3 is catalyzed by SULT1A1, SULT1E1, SULT1A2, and 1A3 (depending on the resveratrol concentration) [Miksits et al., 2005]. The metabolic pathway of resveratrol in human liver cytosol in vitro is shown in Figure 14.4. 

Furthermore, the concept of imbalance between oxidants and antioxidants inherent to oxidative stress led to the implementation of antioxidant therapies and interventions to rebalance the disrupted equilibrium. However, the results of these studies are ambiguous and conflicting and, noteworthy, many molecules with strong antioxidant activity in vitro (such as resveratrol, among many others) revealed effects in vivo not related with antioxidant activity. For instance, resveratrol beyond direct antioxidant activities, and at very low concentrations likely found in vivo, modulates several metabolic pathways in a way that may have a positive impact on human health (Das Das, 2007), in particular the activation of NAD -dependent deacetylases sirtuins (e.g., SlRTl), thus preventing metabolic dysfunctioning (Milne et al, 2007 Elliott Jirousek, 2008). 

Figure 13.3 Pathways of resveratrol absorption, distribution, metabolism, and excretion.

The comparison of different resveratrol levels in LoxS and 35SS fruits allowed the authors to study the effect of the differential depletion of substrates and, in the meantime, to clarify the effect of a novel metabolite as resveratrol on related and unrelated pathways committed to secondary metabolism. 

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