Quercetin

Quercetin

Names
Pronunciation	/ˈkwɜːrsɪtɪn/
IUPAC name 3,3′,4′,5,7-Pentahydroxyflavone
Preferred IUPAC name 2-(3,4-Dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one
Other names 5,7,3′,4′-flavon-3-ol, Sophoretin, Meletin, Quercetine, Xanthaurine, Quercetol, Quercitin, Quertine, Flavin meletin
Identifiers
CAS Number	117-39-5 Y 6151-25-3 (dihydrate)[1] Y
3D model (JSmol)	Interactive image
Beilstein Reference	317313
ChEBI	CHEBI:16243 Y
ChEMBL	ChEMBL50 Y
ChemSpider	4444051 Y
DrugBank	DB04216 Y
ECHA InfoCard	100.003.807
EC Number	204-187-1
Gmelin Reference	579210
IUPHAR/BPS	5346
KEGG	C00389 Y
PubChem CID	5280343
UNII	9IKM0I5T1E Y 53B03V78A6 (dihydrate) Y
UN number	2811
CompTox Dashboard (EPA)	DTXSID4021218
show InChI InChI=1S/C15H10O7/c16-7-4-10(19)12-11(5-7)22-15(14(21)13(12)20)6-1-2-8(17)9(18)3-6/h1-5,16-19,21H Y Key: REFJWTPEDVJJIY-UHFFFAOYSA-N Y InChI=1/C15H10O7/c16-7-4-10(19)12-11(5-7)22-15(14(21)13(12)20)6-1-2-8(17)9(18)3-6/h1-5,16-19,21H Key: REFJWTPEDVJJIY-UHFFFAOYAW
show SMILES O=C1c3c(O/C(=C1/O)c2ccc(O)c(O)c2)cc(O)cc3O
Properties
Chemical formula	C15H10O7
Molar mass	302.236 g/mol
Appearance	yellow crystalline powder[1]
Density	1.799 g/cm3
Melting point	316 °C (601 °F; 589 K)
Solubility in water	Practically insoluble in water; soluble in aqueous alkaline solutions[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N  (what is YN ?)
Infobox references

UV visible spectrum of quercetin, with lambda max at 369 nm.

Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; red onions and kale are common foods containing appreciable amounts of quercetin.^[2] Quercetin 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.^[2] The name has been used since 1857, and is derived from quercetum (oak forest), after the oak genus Quercus.^[3][4] It is a naturally occurring polar auxin transport inhibitor.^[5]

Quercetin is one of the most abundant dietary flavonoids,^[2][6] with an average daily consumption of 25–50 milligrams.^[7]

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.^[9] One study found that organically grown tomatoes had 79% more quercetin than non-organically grown fruit.^[10] Quercetin is present in various kinds of honey from different plant sources.^[11]

Biosynthesis[]

In plants, 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.^[12] 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 using chalcone isomerase.

Naringenin is 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.^[12]

Glycosides[]

3-O-Glycosides of quercetin

Quercetin is the aglycone form of a number of other flavonoid glycosides, such as rutin and quercitrin, found in citrus fruit, buckwheat and onions.^[2] 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.^[13]

Rutin degradation pathway[]

The enzyme quercitrinase can be found in Aspergillus flavus.^[14] This enzyme hydrolyzes the glycoside quercitrin to release quercetin and L-rhamnose. It is an enzyme in the rutin catabolic pathway.^[15]

Pharmacology[]

Pharmacokinetics[]

The bioavailability of quercetin in humans is low and highly variable (0–50%), and it is rapidly cleared with an elimination half-life of 1–2 hours after ingesting quercetin foods or supplements.^[16] Following dietary ingestion, quercetin undergoes rapid and extensive metabolism that makes the biological effects presumed from in vitro studies unlikely to apply in vivo.^[17][18][19]

Quercetin supplements in the aglycone form are far less bioavailable than the quercetin glycoside often found in foods, especially red onions.^[2][20] Ingestion with high-fat foods may increase bioavailability compared to ingestion with low-fat foods,^[20] and carbohydrate-rich foods may increase absorption of quercetin by stimulating gastrointestinal motility and colonic fermentation.^[2]

Metabolism[]

In rats, quercetin did not undergo any significant phase I metabolism.^[21] 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 is methylated by catechol-O-methyltransferase. Four of the five hydroxyl groups of quercetin are glucuronidated by UDP-glucuronosyltransferase. 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, , and .^[21] A methyl metabolite of quercetin has been shown in vitro to be more effective than quercetin at inhibiting lipopolysaccharide-activated macrophages.^[19]

Compared to other flavonoids quercetin is one of the most effective inducers of the phase II detoxification enzymes.^[22]

Quercetin is a strong inhibitor of the cytochrome P450 enzymes CYP3A4 and CYP2D6.^[23] Drugs that are metabolized by these pathways may have increased effect.

In vitro pharmacology[]

Quercetin has been reported to inhibit the oxidation of other molecules and hence is classified as an antioxidant in vitro.^[17] It contains a polyphenolic chemical substructure that stops oxidation in vitro by acting as a scavenger of free radicals. Quercetin has been shown to inhibit the PI3K/AKT pathway leading to downregulation of the anti-apoptotic protein Bcl-w.^[24][25]

Quercetin also activates or inhibits the activities of a number of proteins in vitro. For example, quercetin is a non-specific protein kinase enzyme inhibitor.^[17] In human breast cancer cell lines, quercetin has also been found to act as an agonist of the G protein-coupled estrogen receptor (GPER).^[26]

Health claims[]

Quercetin has been studied in basic research and small clinical trials.^{[2][27][28][29]} While supplements have been promoted for the treatment of cancer and various other diseases,^[2][30] there is no high-quality evidence that quercetin (via supplements or in food) is useful to treat cancer^[31] or any other disease.^[2][32]

The US Food and Drug Administration has issued warning letters to several manufacturers advertising on their product labels and websites that quercetin product(s) can be used to treat diseases.^[33][34] 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 [21 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",^[33][34] conditions which were not met by the manufacturers.

Safety[]

In preliminary human studies, oral intake of quercetin in doses up to one gram per day over three months did not cause adverse effects.^[2] The safety of using quercetin in dietary supplements during pregnancy and lactation has not been established.^[2]

See also[]

References[]

External links[]

• Media related to Quercetin at Wikimedia Commons