Quercetin is a plant
flavonol
Flavonols are a class of flavonoids that have the 3-hydroxyflavone backbone (IUPAC name : 3-hydroxy-2-phenylchromen-4-one). Their diversity stems from the different positions of the phenolic -OH groups. They are distinct from flavanols (with " ...
from the
flavonoid group of
polyphenol
Polyphenols () are a large family of naturally occurring organic compounds characterized by multiples of phenol units. They are abundant in plants and structurally diverse. Polyphenols include flavonoids, tannic acid, and ellagitannin, some o ...
s. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and
kale are common foods containing appreciable amounts of it.
[ It has a bitter flavor and is used as an ingredient in dietary supplements, beverages, and foods.
]
Occurrence
Quercetin is a flavonoid widely distributed in nature.[ The name has been used since 1857, and is derived from ''quercetum'' (oak forest), after the oak genus '']Quercus
An oak is a tree or shrub in the genus ''Quercus'' (; Latin "oak tree") of the beech family, Fagaceae. There are approximately 500 extant species of oaks. The common name "oak" also appears in the names of species in related genera, notably ...
''. It is a naturally occurring polar auxin transport
Polar auxin transport is the regulated transport of the plant hormone auxin in plants. It is an active process, the hormone is transported in cell-to-cell manner and one of the main features of the transport is its asymmetry and directionality ( p ...
inhibitor.
Quercetin is one of the most abundant dietary flavonoids, with an average daily consumption of 25–50 milligram
The kilogram (also kilogramme) is the unit of mass in the International System of Units (SI), having the unit symbol kg. It is a widely used measure in science, engineering and commerce worldwide, and is often simply called a kilo colloquially. ...
s.
In red onions, higher concentrations of quercetin occur in the outermost rings and in the part closest to the root, the latter being the part of the plant with the highest concentration. One study found that organically grown
Organic farming, also known as ecological farming or biological farming,Labelling, article 30 o''Regulation (EU) 2018/848 of the European Parliament and of the Council of 30 May 2018 on organic production and labelling of organic products and re ...
tomato
The tomato is the edible berry of the plant ''Solanum lycopersicum'', commonly known as the tomato plant. The species originated in western South America, Mexico, and Central America. The Mexican Nahuatl word gave rise to the Spanish word ...
es had 79% more quercetin than non-organically grown fruit. Quercetin is present in various kinds of honey
Honey is a sweet and viscous substance made by several bees, the best-known of which are honey bees. Honey is made and stored to nourish bee colonies. Bees produce honey by gathering and then refining the sugary secretions of plants (primar ...
from different plant sources.
Biosynthesis
In plants, phenylalanine is converted to 4-coumaroyl-CoA
Coumaroyl-coenzyme A is the thioester of coenzyme-A and coumaric acid. Coumaroyl-coenzyme A is a central intermediate in the biosynthesis of myriad natural products found in plants. These products include lignols (precursors to lignin and lign ...
in a series of steps known as the general phenylpropanoid pathway using phenylalanine ammonia-lyase
The enzyme phenylalanine ammonia lyase (EC 4.3.1.24) catalyzes the conversion of L-phenylalanine to ammonia and ''trans''-cinnamic acid.:
:L-phenylalanine = ''trans''-cinnamate + NH3
Phenylalanine ammonia lyase (PAL) is the first and committed ...
, cinnamate-4-hydroxylase, and 4-coumaroyl-CoA-ligase. One molecule of 4-coumaroyl-CoA is added to three molecules of malonyl-CoA to form tetrahydroxychalcone using 7,2′-dihydroxy-4′-methoxyisoflavanol synthase. Tetrahydroxychalcone is then converted into naringenin
Naringenin is a flavorless, colorless flavanone, a type of flavonoid. It is the predominant flavanone in grapefruit, and is found in a variety of fruits and herbs.
Structure
Naringenin has the skeleton structure of a flavanone with three hydro ...
using chalcone isomerase
In enzymology, a chalcone isomerase () is an enzyme that catalyzes the chemical reaction
:a chalcone \rightleftharpoons a flavanone
Hence, this enzyme has one substrate, a chalcone, and one product, a flavanone.
This enzyme belongs to the ...
.
Naringenin is converted into eriodictyol
Eriodictyol is a bitter-masking flavanone, a flavonoid extracted from yerba santa (''Eriodictyon californicum''), a plant native to North America. Eriodictyol is one of the four flavanones identified in this plant as having taste-modifying pro ...
using flavanoid 3′-hydroxylase. Eriodictyol is then converted into dihydroquercetin
Taxifolin (5,7,3',4'-flavan-on-ol), also known as dihydroquercetin, belongs to the subclass flavanonols in the flavonoids, which in turn is a class of polyphenols.
Stereocenters
Taxifolin has two stereocenters on the C-ring, as opposed to quer ...
with flavanone 3-hydroxylase, which is then converted into quercetin using flavonol synthase
In enzymology, a flavonol synthase () is an enzyme that catalyzes the following chemical reaction :
dihydroflavonol + 2-oxoglutarate + \rightleftharpoons a flavonol + succinate + C + H2O
The 3 substrates of this enzyme are dihydroflavonol, ...
.
Glycosides
Quercetin is the aglycone An aglycone (aglycon or genin) is the compound remaining after the glycosyl group on a glycoside is replaced by a hydrogen atom. For example, the aglycone of a cardiac glycoside would be a steroid molecule.
Detection
A way to identify aglycone ...
form of a number of other flavonoid glycoside
In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycoside ...
s, such as rutin
Rutin, also called rutoside, quercetin-3-O-rutinoside and sophorin, is the glycoside combining the flavonol quercetin and the disaccharide rutinose (α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranose). It is a flavonoid found in a wide variety of pl ...
(also known as quercetin-3-O-rutinoside) and quercitrin
Quercitrin is a glycoside formed from the flavonoid quercetin and the deoxy sugar rhamnose.
Austrian chemist Heinrich Hlasiwetz (1825-1875) is remembered for his chemical analysis of quercitrin.
Occurrence
Quercitrin is a constituent of the ...
, found in citrus
''Citrus'' is a genus of flowering trees and shrubs in the rue family, Rutaceae. Plants in the genus produce citrus fruits, including important crops such as oranges, lemons, grapefruits, pomelos, and limes. The genus ''Citrus'' is native to ...
fruit, buckwheat
Buckwheat (''Fagopyrum esculentum''), or common buckwheat, is a flowering plant in the knotweed family Polygonaceae cultivated for its grain-like seeds and as a cover crop. The name "buckwheat" is used for several other species, such as ''Fagopy ...
and onions.[ Quercetin forms the ]glycoside
In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycoside ...
s quercitrin
Quercitrin is a glycoside formed from the flavonoid quercetin and the deoxy sugar rhamnose.
Austrian chemist Heinrich Hlasiwetz (1825-1875) is remembered for his chemical analysis of quercitrin.
Occurrence
Quercitrin is a constituent of the ...
and rutin
Rutin, also called rutoside, quercetin-3-O-rutinoside and sophorin, is the glycoside combining the flavonol quercetin and the disaccharide rutinose (α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranose). It is a flavonoid found in a wide variety of pl ...
together with rhamnose and rutinose
Rutinose is the disaccharide also known as 6-''O''-α-L- rhamnosyl-D-glucose (C12H22O10) that is present in some flavonoid glycosides. It is prepared from rutin by hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of wat ...
, respectively. Likewise guaijaverin is the 3-''O''- arabinoside, hyperoside
Hyperoside is a chemical compound. It is the 3-''O''- galactoside of quercetin.
Natural occurrences
Hyperoside has been isolated from ''Drosera rotundifolia'', from the Lamiaceae ''Stachys sp.'' and ''Prunella vulgaris'', from ''Rumex acetosell ...
is the 3-''O''-galactoside
A galactoside is a glycoside containing galactose. The H of the OH group on carbon-1 of galactose is replaced by an organic moiety.
Depending on whether the glycosidic bond lies "above" or "below" the plane of the galactose molecule, galactosides ...
, isoquercitin
Isoquercetin, isoquercitrin or isotrifoliin is a flavonoid, a type of chemical compound. It is the 3-''O''-glucoside of quercetin. Isoquercitrin can be isolated from various plant species including ''Mangifera indica'' (mango) and ''Rheum nobile'' ...
is the 3-''O''- glucoside and spiraeoside
Spiraeoside is a chemical compound. It can be isolated from flowers of ''Filipendula ulmaria'' (L.) (a.k.a. ''Spiraea ulmaria'' or ''meadowsweet'') or from the garden onion (''Allium cepa'').
Spiraeoside is the 4'-O- glucoside of quercetin
Querc ...
is the 4′-''O''-glucoside. CTN-986 is a quercetin derivative found in cottonseeds and cottonseed oil. Miquelianin
Miquelianin (quercetin 3-''O''-glucuronide) is a flavonol glucuronide, a type of phenolic compound present in wine, in species of St John's wort, like ''Hypericum hirsutum'', in ''Nelumbo nucifera'' (Indian lotus) or in green beans.
It is also a ...
is the quercetin 3-''O''-β-D-glucuronopyranoside.
A number of taxifolin
Taxifolin (5,7,3',4'-flavan-on-ol), also known as dihydroquercetin, belongs to the subclass flavanonols in the flavonoids, which in turn is a class of polyphenols.
Stereocenters
Taxifolin has two stereocenters on the C-ring, as opposed to quer ...
(also known as dihydroquercetin) glycosides also exists.
Isoquercetin
Isoquercetin, isoquercitrin or isotrifoliin is a flavonoid, a type of chemical compound. It is the 3-''O''-glucoside of quercetin. Isoquercitrin can be isolated from various plant species including ''Mangifera indica'' (mango) and ''Rheum nobile'' ...
is the 3-''O''-glucoside of quercetin.
Rutin degradation pathway
The enzyme quercitrinase
In enzymology, a quercitrinase () is an enzyme that catalyzes the chemical reaction
:quercitrin + H2O \rightleftharpoons L-rhamnose + quercetin
Thus, the two substrates of this enzyme are quercitrin and H2O, whereas its two products are L- rh ...
can be found in ''Aspergillus flavus
''Aspergillus flavus'' is a saprotrophic and pathogenic fungus with a cosmopolitan distribution. It is best known for its colonization of cereal grains, legumes, and tree nuts. Postharvest rot typically develops during harvest, storage, and/or ...
''. This enzyme hydrolyzes
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysi ...
the glycoside quercitrin
Quercitrin is a glycoside formed from the flavonoid quercetin and the deoxy sugar rhamnose.
Austrian chemist Heinrich Hlasiwetz (1825-1875) is remembered for his chemical analysis of quercitrin.
Occurrence
Quercitrin is a constituent of the ...
to release quercetin and L- rhamnose. It is an enzyme in the rutin
Rutin, also called rutoside, quercetin-3-O-rutinoside and sophorin, is the glycoside combining the flavonol quercetin and the disaccharide rutinose (α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranose). It is a flavonoid found in a wide variety of pl ...
catabolic pathway.
Pharmacology
Pharmacokinetics
The bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...
of quercetin in humans after oral intake is very low, with one study concluding it must be less than 1%. Intravenous injection of quercetin shows a rapid decay in concentration described by a two-compartment model (initial half-life
Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...
of 8.8 minutes, terminal half-life of 2.4 hours). Because it undergoes rapid and extensive metabolism, the biological effects presumed from ''in vitro'' studies are unlikely to apply ''in vivo''. Quercetin supplements in the aglycone An aglycone (aglycon or genin) is the compound remaining after the glycosyl group on a glycoside is replaced by a hydrogen atom. For example, the aglycone of a cardiac glycoside would be a steroid molecule.
Detection
A way to identify aglycone ...
form are less bioavailable
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...
than the quercetin glycoside
In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycoside ...
often found in foods, especially red onions. Ingestion with high-fat foods may increase bioavailability compared to ingestion with low-fat foods, and carbohydrate-rich foods may increase absorption of quercetin by stimulating gastrointestinal motility Gastrointestinal physiology is the branch of human physiology that addresses the physical function of the gastrointestinal (GI) tract. The function of the GI tract is to process ingested food by mechanical and chemical means, extract nutrients and ...
and colonic fermentation.[
]
Metabolism
Quercetin is rapidly metabolized (via glucuronidation
Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gl ...
) after the ingestion of quercetin foods or supplements. Five metabolites (quercetin glucuronides) have been found in human plasma after quercetin ingestion. Taken together, the quercetin glucuronides have a half life around 11-12 hours.
In rats, quercetin did not undergo any significant phase I metabolism. In contrast, quercetin did undergo extensive phase II (conjugation) to produce metabolites that are more polar than the parent substance and hence are more rapidly excreted from the body. In vitro, the meta- hydroxyl group of catechol
Catechol ( or ), also known as pyrocatechol or 1,2-dihydroxybenzene, is a toxic organic compound with the molecular formula . It is the ''ortho'' isomer of the three isomeric benzenediols. This colorless compound occurs naturally in trace amoun ...
is methylated by catechol-O-methyltransferase
Catechol-''O''-methyltransferase (COMT; ) is one of several enzymes that degrade catecholamines (neurotransmitters such as dopamine, epinephrine, and norepinephrine), catecholestrogens, and various drugs and substances having a catechol struct ...
. Four of the five hydroxyl groups of quercetin are glucuronidated
Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosid ...
by UDP-glucuronosyltransferase
Uridine 5'-diphospho-glucuronosyltransferase ( UDP-glucuronosyltransferase, UGT) is a microsomal glycosyltransferase () that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecule. This is ...
. The exception is the 5-hydroxyl group of the flavonoid ring which generally does not undergo glucuronidation. The major metabolites of orally absorbed quercetin are quercetin-3-glucuronide, 3'-methylquercetin-3-glucuronide, and quercetin-3'-sulfate. A methyl metabolite of quercetin has been shown in vitro to be more effective than quercetin at inhibiting lipopolysaccharide
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer ...
-activated macrophages.
Compared to other flavonoids quercetin is one of the most effective inducers of the phase II detoxification enzymes.
In-vitro studies show that quercetin is a strong inhibitor of the cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
enzymes CYP3A4 and CYP2C19
Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some p ...
and a moderate inhibitor of CYP2D6
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.
CYP2D ...
. Drugs that are metabolized by these pathways may have increased effect. An in-vivo study found that quercetin supplementation slows the metabolism of caffeine
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine to ...
to a statistically significant extent in a particular genetic sub-population, but in absolute terms the effect was almost negligible.
Pharmacological research
Quercetin has been reported to inhibit the oxidation
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...
of other molecules and hence is classified as an antioxidant in vitro.[ It contains a ]polyphenol
Polyphenols () are a large family of naturally occurring organic compounds characterized by multiples of phenol units. They are abundant in plants and structurally diverse. Polyphenols include flavonoids, tannic acid, and ellagitannin, some o ...
ic chemical substructure that stops oxidation in vitro by acting as a scavenger of free radical
A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing.
Ageing
Ailments of unknown cause
Biogerontology
Biological processes
Causes of death
Cellular processes
Gerontology
Life extension
Metabo ...
s. Quercetin has been shown to inhibit the PI3K/AKT pathway leading to downregulation
In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary pr ...
of the anti-apoptotic
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes incl ...
protein Bcl-w
Bcl-2-like protein 2 is a 193-amino acid protein that in humans is encoded by the ''BCL2L2'' gene on chromosome 14 (band q11.2-q12). It was originally discovered by Leonie Gibson, Suzanne Cory and colleagues at the Walter and Eliza Hall Institut ...
. Quercetin activates or inhibits the activities of a number of proteins in vitro. For example, it is a nonspecific protein kinase
A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a fu ...
enzyme inhibitor.[
]
Food safety
In 2010, the FDA
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
acknowledged high-purity quercetin as GRAS for use as an ingredient in various specified food categories at levels up to 500 milligrams per serving.
Health claims
Quercetin has been studied in basic research
Basic research, also called pure research or fundamental research, is a type of scientific research with the aim of improving scientific theories for better understanding and prediction of natural or other phenomena. In contrast, applied rese ...
and small clinical trials. While supplements have been promoted for the treatment of cancer and various other diseases, there is no high-quality evidence that quercetin (via supplements or in food) is useful to treat cancer or any other disease.
The US Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
has issued warning letters to several manufacturers advertising on their product labels and websites that quercetin product(s) can be used to treat diseases. The FDA regards such quercetin advertising and products as unapproved – with unauthorized health claims concerning the anti-disease products – as defined by "sections 201(g)(1)(B) and/or 201 (g)(1)(C) of the Act 1 U.S.C. § 321(g)(1)(B) and/or 21 U.S.C. § 321(g)(1)(C)because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease",[ conditions not met by the manufacturers.
]
Safety
There has been little research into the safety of quercetin supplementation in humans, and the results are insufficient to give confidence that the practice is safe. In particular, there is a lack of safety information on the effect of quercetin supplementation for pregnant women, breastfeeding women, children, and adolescents. The hormonal effects of quercetin found in animal studies raise the suspicion of a parallel effect in humans, particularly in respect of estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...
-dependent tumors.[
Quercetin supplementation can interfere with the effects of medications. The precise nature of this interaction is known for some common medicines, but for many, it is not.]
See also
* List of ineffective cancer treatments
This is a non-exhaustive list of alternative treatments that have been promoted to treat or prevent cancer in humans but which lack scientific and medical evidence of effectiveness. In many cases, there is scientific evidence that the alleged tr ...
* Flavonol 3-sulfotransferase
* Phenolic compounds in wine
The phenolic content in wine refers to the phenolic compounds—natural phenol and polyphenols—in wine, which include a large group of several hundred chemical compounds that affect the taste, color and mouthfeel of wine. These compounds include ...
* Phytochemical
* Quercetin 2,3-dioxygenase
* Quercetin 3-O-methyltransferase
* Quercetin-3-sulfate 3'-sulfotransferase
* Quercetin-3-sulfate 4'-sulfotransferase
* Quercetin-3,3'-bissulfate 7-sulfotransferase
References
External links
*
{{Authority control
Aromatase inhibitors
CYP2C8 inhibitors
CYP3A4 inhibitors
Flavonoid antioxidants
GPER agonists
Xanthine oxidase inhibitors
Experimental medical treatments
Phytoestrogens
Selective ERβ agonists