Abstract
The nematode Caenorhabditis elegans has been used to examine the influence of epicatechin (EC), an abundant flavonoid in the human diet, in some stress biomarkers (ROS production, lipid peroxidation and protein carbonylation). Furthermore, the ability of EC to modulate the expression of some key genes in the insulin/IGF-1 signaling pathway (IIS), involved in longevity and oxidative or heat shock stress response, has also been explored. The final aim was to contribute to the elucidation of the mechanisms involved in the biological effects of flavonoids. The results showed that EC-treated wild-type C. elegans exhibited increased survival and reduced oxidative damage of biomolecules when submitted to thermal stress. EC treatment led to a moderate elevation in ROS levels, which might activate endogenous mechanisms of defense protecting against oxidative insult. The enhanced stress resistance induced by EC was found to be mediated through the IIS pathway, since assays in daf-2, age-1, akt-1, akt-2, sgk-1, daf-16, skn-1 and hsf-1 loss of function mutant strains failed to show any heat-resistant phenotype against thermal stress when treated with EC. Consistently, EC treatment upregulated the expression of some stress resistance associated genes, such as gst-4, hsp-16.2 and hsp-70, which are downstream regulated by the IIS pathway.
Highlights
Flavan-3-ols, such as epicatechin (EC), catechin (C) and their oligomers, the procyanidins, represent a major class of secondary polyphenolic plant metabolites
The treatment of C. elegans with epicatechin leads to an increase in the survival of the nematode when subjected to thermal stress, as well as to a decrease in the levels of lipid peroxidation and carbonylated proteins
The influence of reactive oxygen species (ROS) levels on the survival of C. elegans is still under discussion, the results obtained in this study suggest that the moderate elevation in ROS levels produced by EC treatment does not seem to be correlated with detrimental effects
Summary
Flavan-3-ols, such as epicatechin (EC), catechin (C) and their oligomers, the procyanidins, represent a major class of secondary polyphenolic plant metabolites. Flavan-3-ols are among the most abundant flavonoids in the human diet and are mainly present in fruits, tea, cocoa and red wine. These compounds have been reported to exhibit a range of biochemical and pharmacological activities [1], their precise mechanisms of action have not been yet elucidated. It has been assumed that antioxidant and radical scavenging properties underlay their action mechanism, but currently it is not clear whether other pathways contribute to their overall effect and could be even more important than the radical scavenging properties [2].
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