Danesi, F.; Kroon, P.A.; Saha, S.; de Biase, D.; D'Antuono, L.F.; Bordoni, A. Mixed Pro- and Anti-Oxidative Effects of Pomegranate Polyphenols in Cultured Cells. Int. J. Mol. Sci. 2014, 15, 19458-19471.
Abstract
In recent years, the number of scientific papers concerning pomegranate (Punica granatum L.) and its health properties has increased greatly, and there is great potential for the use of bioactive-rich pomegranate extracts as ingredients in functional foods and nutraceuticals. To translate this potential into effective strategies it is essential to further elucidate the mechanisms of the reported bioactivity. In this study HepG2 cells were supplemented with a pomegranate fruit extract or with the corresponding amount of pure punicalagin, and then subjected to an exogenous oxidative stress. Overall, upon the oxidative stress the gene expression and activity of the main antioxidant enzymes appeared reduced in supplemented cells, which were more prone to the detrimental effects than unsupplemented ones. No differences were detected between cells supplemented with the pomegranate juice or the pure punicalagin. Although further studies are needed due to the gaps existing between in vitro andin vivo studies, our results suggest caution in the administration of high concentrations of nutraceutical molecules, particularly when they are administered in concentrated form.
Conclusions
Polyphenols are supposed to have preventive effects for a variety of chronic pathological conditions, and they are often considered safer and more easily integrated into lifestyle changes than conventional pharmaceutical drugs. However, many studies often report biological effects of food polyphenols without elucidating the underlying molecular, cellular, and physiological mechanisms.
Oxidant properties of polyphenols may be both anti-oxidant and/or pro-oxidant based upon the structure of the particular polyphenols, their concentration, and the cellular redox context [33,34]. With moderate and low polyphenol concentrations, low level oxidative stress may be a beneficial cue to initiate induction of protective anti-oxidant systems and boost immune responses; with higher concentration, or in conditions with increased oxidative stress, polyphenol supplementation may exacerbate the detrimental effect of the stress itself. The biological effects of POM extract and PUN observed in this study could represent evidence that high-dose polyphenols can potentially cause adverse effects through pro-oxidative effects, PUN being the most critical pomegranate component.
Although results obtained in vitro cannot be uncritically extrapolated to the in vivo situation, this work suggests caution in the use of very high concentrations of nutraceutical molecules, particularly when administered in concentrated form like in fortified, enhanced, or purified foods and/or dietary supplements food.
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