Quercetin

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Quercetin
Quercetin
Identifiers
CAS number 117-39-5 YesY, 6151-25-3 (Quercetin dihydrate)[1]
PubChem 5280343
ChemSpider 4444051 YesY
UNII 9IKM0I5T1E YesY
DrugBank DB04216
KEGG C00389 YesY
ChEBI CHEBI:16243 N
ChEMBL CHEMBL50 YesY
Jmol-3D images Image 1
Properties
Molecular formula C15H10O7
Molar mass 302.236 g/mol
Appearance yellow crystalline powder[1]
Density 1.799 g/cm3
Melting point 316 °C
Solubility in water Practically insoluble in water; soluble in aqueous alkaline solutions[1]
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox references
UV visible spectrum of quercetin, with lambda max at 369 nm.

Quercetin /ˈkwɜrsɨtɨn/, a flavonol, is a flavonoid, in other words, a plant pigment with a molecular structure like or derived from flavone.[2] It is found in fruits, vegetables, leaves and grains. It can be used as an ingredient in supplements, beverages, or foods.

Occurrence[edit]

Quercetin is a flavonoid widely distributed in nature. The name has been used since 1857, and is derived from quercetum (oak forest), after Quercus.[3][4] It is a naturally occurring polar auxin transport inhibitor.[5]

Foods containing quercetin Quercetin (mg/100g of edible portion)
capers, raw 234[6]
capers, canned 173[6]
lovage 170[6]
dock like sorrel 86[6]
radish leaves 70[6]
carob fiber 58[6]
dill 55[7] (48-110)[8]
cilantro 53[6]
Hungarian wax pepper 51[6]
fennel leaves 48.8[6]
onion, red 32[9]
radicchio 31.5[6]
watercress 30[9]
buckwheat 23[10]
kale 23[9]
chokeberry 19[9]
cranberry 15[9]
lingonberry 13[9]
plums, black 12[9]
cow peas 11[9]
sweet potato 10[9]
blueberry, cultivated 8[9]
sea buckthorn berry 8[9]
rowanberry 7[9]
crowberry 5[9]
prickly pear cactus fruits 5[9]
apples, Red Delicious 4[9]
broccoli 3[9]
bilberry 3[9]
tea, black or green Camellia sinensis 2[9]

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.[11] One study found that organically grown tomatoes had 79% more quercetin than chemically grown fruit.[12] Quercetin is present in various kinds of honey from different plant sources.[13]

Metabolism[edit]

Biosynthesis[edit]

Phenylalanine is converted to 4-coumaroyl-CoA in a series of steps known as the general phenylpropanoid pathway using phenylalanine ammonia-lyase, cinnamate-4-hydroxylase, and 4-coumaroyl-CoA-ligase. 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 using chalcone isomerase. Naringenin is then converted into eriodictyol using flavanoid 3’-hydroxylase. Eriodictyol is then converted into dihydroquercetin with flavanone 3-hydroxylase, which is then converted into quercetin using flavonol synthase.[14]

Quercetin release in the rutin degradation pathway[edit]

The enzyme quercitrinase can be found in Aspergillus flavus.[15] Its substrates are quercitrin and H2O and releases quercetin and L-rhamnose. It is an enzyme in the rutin catabolic pathway[16]

Conjugates[edit]

Quercetin 3-O-sulfate is a human plasma quercetin metabolite.

Glycosides[edit]

Quercetin is the aglycone form of a number of other flavonoid glycosides, such as rutin and quercitrin, found in citrus fruit, buckwheat and onions. Quercetin forms the glycosides quercitrin and rutin together with rhamnose and rutinose, respectively. Likewise guaijaverin is the 3-O-arabinoside, hyperoside is the 3-O-galactoside, isoquercitin is the 3-O-glucoside and spiraeoside is the 4'-O-glucoside. CTN-986 is a quercetin derivative found in cottonseeds and cottonseed oil. Miquelianin is the quercetin 3-o-β-d-glucuronopyranoside.[17]

Study of metabolism using Cunninghamella elegans[edit]

Cunninghamella elegans is a fungal model of mammalian drug metabolism. It can be used to study the quercetin biodegradation.[18]

Effects of consumption by humans and other animals[edit]

Quercetin itself (aglycone quercetin), as opposed to quercetin glycosides, is not a normal dietary component. In a bioavailability study in rats, radiolabelled quercetin-4'-glucoside was converted to phenolic acids as it passed through the gastrointestinal tract, producing compounds not monitored in previous animal studies of aglycone quercetin.[19] All but 4% was recovered within 72 hours (69% in urine), indicating low retention and high excretion, a characteristic of ingested polyphenols. Quercetin may also induce insulin secretion by activation of L-type calcium channels in the pancreatic β-cells.[20] Quercetin has not been confirmed scientifically as a specific therapeutic for any condition nor approved by any regulatory agency. The U.S. Food and Drug Administration has not approved any health claims for quercetin.[21]

Preliminary research[edit]

Antiviral[edit]

Hyperoside (which is the 3-O-galactoside of quercetin) is a strong inhibitor of HBsAg and HBeAg secretion in 2.2.15 cells.[22]

Quercitrin and myricetin 3-O-beta-D-galactopyranoside inhibit HIV-1 reverse transcriptase, all with IC50 values of 60 μM.[23]

Quercetin can also inhibit reverse transcriptase, part of the replication process of retroviruses.[24] The therapeutic relevance of this inhibition has not been established.

Asthma[edit]

Quercetin is an effective bronchodilator and helps reduce the release of histamine and other allergic or inflammatory chemicals in the body.[25]

Quercetin has demonstrated significant anti-inflammatory activity because of direct inhibition of several initial processes of inflammation.[26]

Cancer[edit]

Laboratory studies have investigated Quercetin's potential for use in anti-cancer applications.[27] The American Cancer Society says while quercetin "has been promoted as being effective against a wide variety of diseases, including cancer," and "some early lab results appear promising, as of yet there is no reliable clinical evidence that quercetin can prevent or treat cancer in humans." In the amounts consumed in a healthy diet, quercetin "is unlikely to cause any major problems or benefits."[28]

Eczema[edit]

Serum IgE levels are highly elevated in eczema patients, and virtually all eczema patients are positive for allergy testing. Excessive histamine release can be minimized by the use of antioxidants. Quercetin has been shown to be effective in reducing IgE levels in rodent models.[29]

Inflammation[edit]

Several laboratory studies show quercetin may have anti-inflammatory properties,[30][31] and it is being investigated for a wide range of potential health benefits.[31][32]

Quercetin has been reported to be of use in alleviating symptoms of pollinosis.[33] An enzymatically modified derivative was found to alleviate ocular but not nasal symptoms of pollinosis.[34][35][36]

Studies done in test tubes have shown quercetin may prevent immune cells from releasing histamines which might influence symptoms of allergies.[37][38]

A study with rats showed that quercetin effectively reduced immediate-release niacin (vitamin B3) flush, in part by means of reducing prostaglandin D2 production.[39] A pilot clinical study of four humans gave preliminary data supporting this.[40]

Quercetin may have properties of a calcineurin inhibitor, similar to cyclosporin A and tacrolimus, according to one laboratory study.[41]

Fibromyalgia[edit]

Quercetin may be effective in the treatment of fibromyalgia because of its potential anti-inflammatory or mast cell inhibitory properties shown in laboratory studies.[42]

Metabolic syndrome[edit]

Quercetin has been shown to increase energy expenditure in rats, but only for short periods (fewer than 8 weeks).[30] Effects of quercetin on exercise tolerance in mice have been associated with increased mitochondrial biogenesis.[31] In mice, an oral quercetin dose of 12.5 to 25 mg/kg increased gene expression of mitochondrial biomarkers and improved exercise endurance.[31]

It has also been claimed that quercetin reduces blood pressure in hypertensive[43] and obese subjects in whom LDL cholesterol levels were also reduced.[44]

In vitro studies showed quercetin and resveratrol combined inhibited production of fat cells[45] and vascular smooth muscle cell proliferation.[46]

Supplements of quercetin with vitamin C and niacin does not cause any significant difference in body mass or composition[47] and has no significant effect on inflammatory markers, diagnostic blood chemistries, blood pressure, and blood lipid profiles.[48]

Monoamine-oxidase inhibitor[edit]

Possibly an active component of heather (Calluna vulgaris), quercetin was suspected from a bioassay test on crude extracts to selectively inhibit monoamine oxidase, possibly indicating pharmacological properties.[49]

Prostatitis[edit]

Quercetin has been found to provides significant symptomatic improvement in most men with chronic prostatitis, a condition also known as male chronic pelvic pain syndrome.[50]

Drug interactions[edit]

Quercetin is contraindicated with some antibiotics; it may interact with fluoroquinolones (an antibiotic), as quercetin competitively binds to bacterial DNA gyrase. Whether this inhibits or enhances the effect of fluoroquinolones is not certain.[51]

AHFS Drug Information (2010)[52] identifies quercetin as an inhibitor of CYP2C8, and specifically names it as a drug with potential to have harmful interactions with taxol/paclitaxel. As paclitaxel is metabolized primarily by CYP2C8, its bioavailability may be increased unpredictably, potentially leading to harmful side-effects.[53][54]

Quercetin is described as an inhibitor of CYP2C9.[55] Quercetin is an inhibitor[56] and inducer[57] of CYP3A4 (in other words, it reduces the enzyme's activity in the short term, but the body responds by producing more of it). CYP2C9 and CYP3A4 are members of the cytochrome P450 mixed-function oxidase system, and as such are enzymes involved in the metabolism of xenobiotics in the body. In either case, quercetin may alter serum levels and, therefore, effects of drugs metabolized by these enzymes.

See also[edit]

References[edit]

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External links[edit]