Review
Health effects of quercetin: From antioxidant to nutraceutical

https://doi.org/10.1016/j.ejphar.2008.03.008 Get rights and content

Abstract

Quercetin, a member of the flavonoids family, is one of the most prominent dietary antioxidants. It is ubiquitously present in foods including vegetables, fruit, tea and wine as well as countless food supplements and is claimed to exert beneficial health effects. This includes protection against various diseases such as osteoporosis, certain forms of cancer, pulmonary and cardiovascular diseases but also against aging. Especially the ability of quercetin to scavenge highly reactive species such as peroxynitrite and the hydroxyl radical is suggested to be involved in these possible beneficial health effects. Consequently, numerous studies have been performed to gather scientific evidence for these beneficial health claims as well as data regarding the exact mechanism of action and possible toxicological aspects of this flavonoid. The purpose of this review is to evaluate these studies in order to elucidate the possible health-beneficial effects of the antioxidant quercetin. Firstly, the definitions as well as the most important aspects regarding free radicals, antioxidants and oxidative stress will be discussed as background information. Subsequently, the mechanism by which quercetin may operate as an antioxidant (tested in vitro) as well as the potential use of this antioxidant as a nutraceutical (tested both ex vivo and in vivo) will be discussed.

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)

  • BootsA.W. et al.

    The quercetin paradox

    FEBS Lett.

    (2007)
  • BuckiR. et al.

    Flavonoid inhibition of platelet proagulant activity and phosphoinositide synthesis

    J. Thromb. Haemost.

    (2003)
  • BurkeV. et al.

    Clustering of health-related behaviors among 18-year-old Australians

    Prev. Med.

    (1997)
  • ChaudiereJ. et al.

    Intracellular antioxidants: from chemical to biochemical mechanisms

    Food Chem. Toxicol.

    (1999)
  • ConquerJ.A. et al.

    Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects

    J. Nutr.

    (1998)
  • CushnieT.P. et al.

    Antimicrobial activity of flavonoids

    Int. J. Antimicrob. Agents

    (2005)
  • DayA.J. et al.

    Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver beta-glucosidase activity

    FEBS Lett.

    (1998)
  • DayA.J. et al.

    Conjugation position of quercetin glucuronides and effect on biological activity

    Free Radic. Biol. Med.

    (2000)
  • DayA.J. et al.

    Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase

    FEBS Lett.

    (2000)
  • de BoerV.C. et al.

    Tissue distribution of quercetin in rats and pigs

    J. Nutr.

    (2005)
  • de WhalleyC.V. et al.

    Flavonoids inhibit the oxidative modification of low density lipoproteins by macrophages

    Biochem. Pharmacol.

    (1990)
  • EdwardsR. et al.

    Quercetin reduces blood pressure in hypertensive subjects

    J. Nutr.

    (2007)
  • FloheL. et al.

    Redox regulation of NF-kappa B activation

    Free Radic. Biol. Med.

    (1997)
  • GalatiG. et al.

    Peroxidative metabolism of apigenin and naringenin versus luteolin and quercetin: glutathione oxidation and conjugation

    Free Radic. Biol. Med.

    (2001)
  • GazianoJ.M. et al.

    Supplementation with beta-carotene in vivo and in vitro does not inhibit low density lipoprotein oxidation

    Atherosclerosis

    (1995)
  • GeeJ.M. et al.

    Quercetin glucosides interact with the intestinal glucose transport pathway

    Free Radic. Biol. Med.

    (1998)
  • GeeJ.M. et al.

    Intestinal transport of quercetin glycosides in rats involves both deglycosylation and interaction with the hexose transport pathway

    J. Nutr.

    (2000)
  • GeraetsL. et al.

    Dietary flavones and flavonoles are inhibitors of poly(ADP-ribose)polymerase-1 in pulmonary epithelial cells

    J. Nutr.

    (2007)
  • Ginn-PeaseM.E. et al.

    Redox signals and NF-kappaB activation in T cells

    Free Radic. Biol. Med.

    (1998)
  • HaenenG.R.M.M. et al.

    Nitric oxide radical scavenging of flavonoids

    Methods Enzymol.

    (1999)
  • HaenenG.R.M.M. et al.

    Peroxynitrite scavenging by flavonoids

    Biochem. Biophys. Res. Commun.

    (1997)
  • HaenenG.R. et al.

    4-Hydroxy-2,3-trans-nonenal stimulates microsomal lipid peroxidation by reducing the glutathione-dependent protection

    Arch. Biochem. Biophys.

    (1987)
  • HalliwellB.

    Free radicals, antioxidants, and human disease: curiosity, cause, or consequence?

    Lancet

    (1994)
  • HalliwellB.

    Antioxidant characterization. Methodology and mechanism

    Biochem. Pharmacol.

    (1995)
  • HalliwellB. et al.

    Lipid peroxidation: its mechanism, measurement and significance

    Am. J. Clin. Nutr.

    (1993)
  • HamptonM.B. et al.

    Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing

    Blood

    (1998)
  • HanasakiY. et al.

    The correlation between active oxygens scavenging and antioxidative effects of flavonoids

    Free Radic. Biol. Med.

    (1994)
  • HavsteenB.

    Flavonoids, a class of natural products of high pharmacological potency

    Biochem. Pharmacol.

    (1983)
  • HeijnenC.G. et al.

    Flavonoids as peroxynitrite scavengers: the role of the hydroxyl groups

    Toxicol. In Vitro

    (2001)
  • HertogM.G.L. et al.

    Antioxidant flavonols and coronary heart disease risk

    Lancet

    (1997)
  • HevelJ.M. et al.

    Purification of the inducible murine macrophage nitric oxide synthase. Identification as a flavoprotein

    J. Biol. Chem.

    (1991)
  • HollmanP.C. et al.

    Absorption, metabolism and health effects of dietary flavonoids in man

    Biomed. Pharmacother.

    (1997)
  • HollmanP.C. et al.

    Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers

    Am. J. Clin. Nutr.

    (1995)
  • HollmanP.C. et al.

    Absorption and disposition kinetics of the dietary antioxidant quercetin in man

    Free Radic. Biol. Med.

    (1996)
  • HollmanP.C. et al.

    Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man

    FEBS Lett.

    (1997)
  • ItoS. et al.

    Covalent binding of catechols to proteins through the sulphydryl group

    Biochem. Pharmacol.

    (1988)
  • F. Antonicelli et al.

    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.

    (2000)
  • W.P. Arnold et al.

    Nitric oxide activates guanylate cyclase and increases guanosine 3′:5′-cyclic monophosphate levels in various tissue preparations

    Proc. Natl. Acad. Sci. U. S. A.

    (1977)
  • I.C. Arts et al.

    Quercetin-3-glucoside is transported by the glucose carrier SGLT1 across the brush border membrane of rat small intestine

    J. Nutr.

    (2002)
  • M. Aslan et al.

    Oxidants in receptor tyrosine kinase signal transduction pathways

    Antioxid. Redox Signal.

    (2003)
  • Cited by (1567)

    View all citing articles on Scopus
    View full text