Exploring Target Genes Involved in the Effect of Quercetin on the Response to Oxidative Stress in Caenorhabditis elegans

Abstract

Quercetin is one the most abundant flavonoids in the human diet. Although it is well known that quercetin exhibits a range of biological activities, the mechanisms behind these activities remain unresolved. The aim of this work is to progress in the knowledge of the molecular mechanisms involved in the biological effects of quercetin using Caenorhabditis elegans as a model organism. With this aim, the nematode has been used to explore the ability of this flavonoid to modulate the insulin/insulin-like growth factor 1(IGF-1) signaling pathway (IIS) and the expression of some genes related to stress response. Different methodological approaches have been used, i.e., assays in knockout mutant worms, gene expression assessment by RT-qPCR, and C. elegans transgenic strains expressing green fluorescent protein (GFP) reporters. The results showed that the improvement of the oxidative stress resistance of C. elegans induced by quercetin could be explained, at least in part, by the modulation of the insulin signaling pathway, involving genes age-1, akt-1, akt-2, daf-18, sgk-1, daf-2, and skn-1. However, this effect could be independent of the transcription factors DAF-16 and HSF-1 that regulate this pathway. Moreover, quercetin was also able to increase expression of hsp-16.2 in aged worms. This observation could be of particular interest to explain the effects of enhanced lifespan and greater resistance to stress induced by quercetin in C. elegans, since the expression of many heat shock proteins diminishes in aging worms.

A Polyphenol-Rich Fraction from Eugenia uniflora Exhibits Antioxidant and Hepatoprotective Activities In Vivo

“…These activities are attributed to the presence of several polyphenols, among them quercetin and myricetin glucosides. Our results are in agreement with a study by Durán et al [25], where the authors reported that quercetin exhibits antioxidant activities in C. elegans that are DAF-16-independent. Additionally, another study by Büchter et al revealed that myricetin exhibits antioxidant activities through nuclear translocation of DAF-16 [26].…”

Mulberry Leaf Flavonoids Improve Milk Production, Antioxidant, and Metabolic Status of Water Buffaloes

“…Mulberry leaf flavonoids have shown to increase the nutrient digestibility, dietary metabolizable energy, and rumen fermentation in pre and post-weaning calves (70,90). The desirable effects of MLF on lactation performance observed in the present study may be attributed to the increased secretion of metabolic hormones and modulation of the insulin/IGF-1 signaling pathway (91).…”

Caenorhabditis elegans as a Model Organism to Evaluate the Antioxidant Effects of Phytochemicals

“…Oxidative stress can also be induced by submitting C. elegans to a temperature of 32–37 °C [ 57 ]. The application of a thermal stress has also been commonly used to assess the antioxidant potential of polyphenols in C. elegans [ 21 , 22 , 58 , 59 , 60 , 61 , 62 ].…”

“…The evolutionary conserved insulin/insulin like growth factor-1 (IGF-1) signaling pathway controls many important biological processes, such as ageing, metabolism or stress resistance throughout species [ 19 , 20 ]. This pathway has been repeatedly proposed as a key target in the biological effects of different polyphenols [ 21 , 22 , 23 , 24 , 25 ]. Also, the activation of mitogen-activated protein kinases (MAPK) and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway has been indicated as a mechanism by which polyphenols might influence energy homeostasis and inflammatory processes [ 13 ].…”