ReviewHealth effects of quercetin: From antioxidant to nutraceutical
Section snippets
Origin and terminology
Free radicals are reactive molecules due to the presence of one or more unpaired electron(s). They are formed in the human body either as an essential mediator in vital processes including neurotransmission and inflammatory reactions, or as a byproduct that does not have a role in the actual process. In aerobic life forms, the reduction of oxygen is of special interest. This reduction comprises binding of most of the oxygen to hydrogen to give water, a process involved in the oxidative
Antioxidants
Fortunately, the human body comprises an elaborate antioxidant defense system to protect cellular compounds from damage induced by free radicals, ROS and other reactive species. An antioxidant has been defined as “any substance that, when present in low concentrations compared to that of an oxidizable substrate, significantly delays or inhibits the oxidation of that substrate” (Sies, 1993, Halliwell, 1995). The antioxidants that react directly with radicals or other reactive species to prevent
Oxidative stress
In normal situations, the endogenous antioxidant network as described earlier provides sufficient protection against reactive species such as ROS and RNS (Bast et al., 1991). However, when an imbalance between the production of and the protection against reactive species occurs in favor of the production, a situation called oxidative stress arises (Fig. 4). Oxidative stress may result in increased oxidative damage and can be caused either by an overproduction of free radicals and ROS or by an
Antioxidant therapy
Due to their ability to scavenge free radicals and reactive species, thereby reducing oxidative stress and associated damage, various health claims have been made regarding the use of exogenous, dietary antioxidants (Halliwell, 1996b, Diplock et al., 1998). As a result, numerous studies have been performed to examine the possible beneficial health effects of antioxidant supplementation. However, most of these studies have been conducted with healthy volunteers, i.e. people with a sufficient
Possible candidates for antioxidant therapy: flavonoids
A group of antioxidants that is often suggested to be good candidates for antioxidant therapy due to their potential role in supporting health are the flavonoids. Flavonoids are a class of naturally occurring polyphenolic compounds, ubiquitously present in photosynthesising cells (Saito, 1974, Salunkhe et al., 1982). Over 5000 different naturally occurring flavonoids have already been identified and the list is still growing (Middleton and Kandaswami, 1993, Shahidi and M., 1995). Flavonoids are
Absorption, metabolism and bio-availability
Because of the hydrophilic character of its glycosides, only quercetin without a sugar group, i.e. the aglycon, was initially suggested to be taken up in the gastro-intestinal tract by passive diffusion (Kuhnau, 1976, Griffiths, 1982). However, a study with human ileostomy volunteers showed not only that quercetin glycosides can indeed be absorbed in the small intestine, but also that this absorption surpasses that of the aglycon by far, i.e. 52% of the glycosides was absorbed versus 24% of the
Conclusions
The flavonoid quercetin has been proven to be an excellent antioxidant that also possesses anti-inflammatory, anti-proliferative and gene expression changing capacities in vitro (Fig. 9). Until now, only its antioxidative and anti-inflammatory effects have been shown in vivo as well. Interestingly, these two effects of quercetin appear to be more pronounced when the basal levels of respectively the occurring oxidative stress and inflammation are high. This indicates that the use of quercetin
Implications
As stated above, the dose-dependent safety of the (long term) use of quercetin in vivo should be examined in more detail before any recommendation regarding the use of this flavonoid as a nutraceutical can be made. Since it can be expected that antioxidant therapy will be mainly applied in patients suffering from chronic diseases that are associated with ongoing damage, chronic use of such supplementation will most likely be required. Up to date, there are no data available regarding the safety
References (195)
- et al.
Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the alpha-tocopherol beta-carotene cancer prevention study
Am. J. Clin. Nutr.
(1995) - et al.
Polyphenols and disease risk in epidemiologic studies
Am. J. Clin. Nutr.
(2005) - et al.
A new approach to assess the total antioxidant capacity using the TEAC assay
Food Chem.
(2004) Phagocytes and oxidative stress
Am. J. Med.
(2000)- et al.
Interleukin-8, a chemotactic and inflammatory cytokine
FEBS Lett.
(1992) Is formation of reactive oxygen by cytochrome P450 perilous and predictable?
Trends Pharmacol. Sci.
(1986)- et al.
The toxicity of antioxidants and their metabolites
Environ. Toxicol. Pharmacol.
(2002) - et al.
Oxidative damage shifts from lipid peroxidation to thiol arylation by catechol-containing antioxidants
Biochim. Biophys. Acta.
(2002) - et al.
Oxidized quercetin reacts with thiols rather than with ascorbate: implication for quercetin supplementation
Biochem. Biophys. Res. Commun.
(2003) - et al.
The reversibility of the glutathionyl-quercetin adduct spreads oxidized quercetin-induced toxicity
Biochem. Biophys. Res. Commun.
(2005)
The quercetin paradox
FEBS Lett.
Flavonoid inhibition of platelet proagulant activity and phosphoinositide synthesis
J. Thromb. Haemost.
Clustering of health-related behaviors among 18-year-old Australians
Prev. Med.
Intracellular antioxidants: from chemical to biochemical mechanisms
Food Chem. Toxicol.
Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects
J. Nutr.
Antimicrobial activity of flavonoids
Int. J. Antimicrob. Agents
Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver beta-glucosidase activity
FEBS Lett.
Conjugation position of quercetin glucuronides and effect on biological activity
Free Radic. Biol. Med.
Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase
FEBS Lett.
Tissue distribution of quercetin in rats and pigs
J. Nutr.
Flavonoids inhibit the oxidative modification of low density lipoproteins by macrophages
Biochem. Pharmacol.
Quercetin reduces blood pressure in hypertensive subjects
J. Nutr.
Redox regulation of NF-kappa B activation
Free Radic. Biol. Med.
Peroxidative metabolism of apigenin and naringenin versus luteolin and quercetin: glutathione oxidation and conjugation
Free Radic. Biol. Med.
Supplementation with beta-carotene in vivo and in vitro does not inhibit low density lipoprotein oxidation
Atherosclerosis
Quercetin glucosides interact with the intestinal glucose transport pathway
Free Radic. Biol. Med.
Intestinal transport of quercetin glycosides in rats involves both deglycosylation and interaction with the hexose transport pathway
J. Nutr.
Dietary flavones and flavonoles are inhibitors of poly(ADP-ribose)polymerase-1 in pulmonary epithelial cells
J. Nutr.
Redox signals and NF-kappaB activation in T cells
Free Radic. Biol. Med.
Nitric oxide radical scavenging of flavonoids
Methods Enzymol.
Peroxynitrite scavenging by flavonoids
Biochem. Biophys. Res. Commun.
4-Hydroxy-2,3-trans-nonenal stimulates microsomal lipid peroxidation by reducing the glutathione-dependent protection
Arch. Biochem. Biophys.
Free radicals, antioxidants, and human disease: curiosity, cause, or consequence?
Lancet
Antioxidant characterization. Methodology and mechanism
Biochem. Pharmacol.
Lipid peroxidation: its mechanism, measurement and significance
Am. J. Clin. Nutr.
Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing
Blood
The correlation between active oxygens scavenging and antioxidative effects of flavonoids
Free Radic. Biol. Med.
Flavonoids, a class of natural products of high pharmacological potency
Biochem. Pharmacol.
Flavonoids as peroxynitrite scavengers: the role of the hydroxyl groups
Toxicol. In Vitro
Antioxidant flavonols and coronary heart disease risk
Lancet
Purification of the inducible murine macrophage nitric oxide synthase. Identification as a flavoprotein
J. Biol. Chem.
Absorption, metabolism and health effects of dietary flavonoids in man
Biomed. Pharmacother.
Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers
Am. J. Clin. Nutr.
Absorption and disposition kinetics of the dietary antioxidant quercetin in man
Free Radic. Biol. Med.
Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man
FEBS Lett.
Covalent binding of catechols to proteins through the sulphydryl group
Biochem. Pharmacol.
LPS stimulation of IL-8 release is inhibited by thiol antioxidant at the transcriptional level in THP-1 macrophage cells
Am. J. Respir. Crit. Care Med.
Nitric oxide activates guanylate cyclase and increases guanosine 3′:5′-cyclic monophosphate levels in various tissue preparations
Proc. Natl. Acad. Sci. U. S. A.
Quercetin-3-glucoside is transported by the glucose carrier SGLT1 across the brush border membrane of rat small intestine
J. Nutr.
Oxidants in receptor tyrosine kinase signal transduction pathways
Antioxid. Redox Signal.
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