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NutrInsight • Do we need dietary polyphenols for health?
3.1 Antioxidant activities of polyphenols
Direct antioxidant activities?
The antioxidant hypothesis is the term used to describe the oxidative damage to important molecules such as proteins, lipids, and DNA which accumulates with ageing. This can lead to the pathogenesis of many age-related diseases such as CVD [Hollman et al., 2011]. The moieties producing the damage range from the highly reactive hydroxyl radical (OH) with a short half-life to the less reactive oxygen and nitrogen species with longer half-lives which are able to diffuse from their initial site of origin. These oxidants are counterbalanced by a range of antioxidant systems, mainly consisting of enzymes but with some low molecular weight antioxidants. Some enzymes interact directly with oxidants such as catalase, glutathione peroxidase/reductase, and superoxide dismutase and some contribute indirectly to counteract oxidation at target sites e.g. quinone reductases. There is also a support system of ancillary antioxidant enzymes such as transport systems, metabolizing and conjugating enzymes (Phase I and Phase II).
A direct antioxidant effect for polyphenols in vivo is now thought to be unlikely. Why?
- As discussed in Chapter 1, polyphenols have a limited bioavailability and only very low concentrations (nM) are present in the blood stream and tissues after ingestion of polyphenols compared with other endogenous and exogenous antioxidants. In contrast, most of the in vitro studies have used polyphenols at non physiological doses ( μmol/L to mmol/L),
- Further, the extensive metabolism of polyphenols during absorption and distribution in the body modifies the structure of the polyphenols which highly impact their bioavailability and their biological activity [Visioli et al., 2011].
Now considering the present evidence on physiological effects of polyphenols, it appears that a direct effect of polyphenols is questionable due to the very low concentrations in plasma. However, presently, no evidence allow to attribute the beneficial physiological effects to a direct antioxidant effects rather than other mechanisms of action [Visioli et al., 2011; Hollman et al., 2011].
Indirect antioxidant activities of polyphenols
Some phytochemicals, including polyphenols, are processed by the body as xenobiotics. They stimulate stress-related cell signalling pathways that result in increased expression of genes encoding cytoprotective genes. One example of a transcription factor is Nrf2 (nuclear factor erythroid-2-related factor). It binds to the Antioxidant Response Element (ARE) in cells and thus regulates enzymes involved in antioxidant functions or detoxification (e.g. thioredoxin reductase-1 and glutathione peroxidases).
Polyphenols might increase gene transcription of Nrf2 mediated by such response elements [Yang et al, 2011; Scapagnini et al, 2011] (Figure 10). This provides grounds for the theory of hormesis, i.e. when mild stress triggers defence mechanisms. In the case of polyphenols it indicates how they could have an indirect antioxidant action [Visioli et al., 2011].
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