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
Exact mass 302.042653 u
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]
 N (verify) (what is: YesY/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Quercetin /ˈkwɜrsɨtɨn/, a flavonol, is a plant-derived flavonoid found in fruits, vegetables, leaves and grains. It also may be used as an ingredient in supplements, beverages or foods.

Contents

Occurrence

Quercetin is a flavonoid widely distributed in nature. The name has been used since 1857, and is derived from quercetum (oak forest), after Quercus.[2][3] It is a naturally-occurring polar auxin transport inhibitor.[4]

Foods rich in quercetin include black and green tea (Camellia sinensis; 2000–2500 mg/kg), capers (1800 mg/kg),[5] lovage (1700 mg/kg), apples (44 mg/kg), onion, especially red onion (191 mg/kg) (higher concentrations of quercetin occur in the outermost rings[6]), red grapes, citrus fruit, tomato, broccoli and other leafy green vegetables, and a number of berries, including raspberry, bog whortleberry (158 mg/kg, fresh weight), lingonberry (cultivated 74 mg/kg, wild 146 mg/kg), cranberry (cultivated 83 mg/kg, wild 121 mg/kg), chokeberry (89 mg/kg), sweet rowan (85 mg/kg), rowanberry (63 mg/kg), sea buckthorn berry (62 mg/kg), crowberry (cultivated 53 mg/kg, wild 56 mg/kg),[7] and the fruit of the prickly pear cactus. A recent study found that organically grown tomatoes had 79% more quercetin than "conventionally grown".[8]

A study[9] by the University of Queensland, Australia has also indicated the presence of quercetin in varieties of honey, including honey derived from eucalyptus and tea tree flowers.[10]

Biosynthesis

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.[11]

Glycosides

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.

Effects of consumption by humans and other animals

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 several previous animal studies of aglycone quercetin. All but 4% of the radiolabel was recovered within 72 hours, with 69% recovered in urine.[12]

Quercetin has neither been confirmed scientifically as a specific therapeutic for any condition nor been approved by any regulatory agency. The U.S. Food and Drug Administration has not approved any health claims for quercetin.[13]

Preliminary research

Antiviral

In a 2007 study that assessed the anti-Hepatitis B effects of Hyperoside, and that was published in the Acta Pharmacologica Sinica, it was shown that Hyperoside (which is the 3-O-galactoside of quercetin) is a strong inhibitor of HBsAg and HBeAg secretion in 2.2.15 cells. [14]

In another study also published in 2007 in the Archives of Pharmacal Research it was shown that quercetin, quercitrin and myricetin 3-O-beta-D-galactopyranoside displayed inhibition against HIV-1 reverse transcriptase, all with IC50 values of 60 microM. [15]

Cancer

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."[16]

In laboratory studies of cells in vitro, quercetin produces changes that are also produced by compounds that cause cancer (carcinogens), but these studies do not report increased cancer in animals or humans.[17][18][19]

From laboratory studies is conjecture that quercetin may affect certain mechanisms of cancer.[20][21] An 8-year study found the presence of three flavonols — kaempferol, quercetin, and myricetin — in a normal diet was associated with 23% reduced risk of pancreatic cancer, a rare but frequently fatal disease, in tobacco smokers.[22] There was no benefit in subjects who had never smoked or had previously quit smoking.

In vitro, cultured skin and prostate cancer cells were suppressed (compared to nonmalignant cells) when treated with a combination of quercetin and ultrasound.[23]

Quercetin has been shown to increase the sensitivity of resistant colorectal tumors (CRC) with microsatellite instability (MSI) to the chemotherapy drug 5-fluorouracil (5-FU).[24]

Inflammation

Several laboratory studies show quercetin may have anti-inflammatory properties,[25][26] and it is being investigated for a wide range of potential health benefits.[26][27]

Quercetin has been reported to be of use in alleviating symptoms of pollinosis.[28] An enzymatically modified derivative was found to alleviate ocular but not nasal symptoms of pollinosis.[29][30][31]

A study with rats showed that quercetin effectively reduced immediate-release niacin (vitamin B3) flush, in part by means of reducing prostaglandin D2 production.[32] A pilot clinical study of four humans gave preliminary data supporting this.[33]

Quercetin may have properties of a calcineurin inhibitor, similar to cyclosporin A and tacrolimus, according to one laboratory study.[34]

Metabolic syndrome

Quercetin has been shown to increase energy expenditure in rats, but only for short periods (fewer than 8 weeks).[25] Effects of quercetin on exercise tolerance in mice have been associated with increased mitochondrial biogenesis.[26] In mice, an oral quercetin dose of 12.5 to 25 mg/kg increased gene expression of mitochondrial biomarkers and improved exercise endurance.[35]

It has also been claimed that quercetin reduces blood pressure in hypertensive[36] and obese subjects in whom LDL cholesterol levels were also reduced.[37]

An in vitro study showed quercetin and resveratrol combined inhibited production of fat cells.[38]

A 12-week study of 941 adults found that supplements of 500 to 1000 milligrams of quercetin with vitamin C and niacin did not cause any significant difference in body mass or composition[39] and had no significant effect on inflammatory markers, diagnostic blood chemistries, blood pressure, and blood lipid profiles.[40]

Drug interactions

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.[41]

AHFS Drug Information (2010)[42] 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.[43][44]

Quercetin is described as an inhibitor of CYP2C9.[45] Quercetin is an inhibitor[46] and inducer[47] 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 CPY3A4 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.

References

  1. ^ a b c Quercetin dihydrate safety sheet on http://www.pvp.com.br (English)
  2. ^ "Quercetin". Merriam-Webster. http://www.merriam-webster.com/dictionary/quercetin. 
  3. ^ "Quercitin (biochemistry)". Encyclopedia Brittanica. http://www.britannica.com/EBchecked/topic/487030/quercitin. 
  4. ^ Christiane Fischer, Volker Speth, Sonja Fleig-Eberenz, and Gunther Neuhaus (1999-10). "lnduction of Zygotic Polyembryos in Wheat: lnfluence of Auxin Polar Transport". Plant Cell 9 (10): 1767–1780. doi:10.1105/tpc.9.10.1767. PMC 157020. PMID 12237347. http://www.plantcell.org/content/9/10/1767.full.pdf. 
  5. ^ USDA Database for the Flavonoid Content of Selected Foods
  6. ^ Crystal Smith, Kevin A. Lombard, Ellen B. Peffley, Weixin Liu (2003). "Genetic Analysis of Quercetin in Onion (Allium cepa L.) Lady Raider". The Texas Journal of Agriculture and Natural Resource (Agriculture Consortium of Texas) 16: 24–8. Archived from the original on February 25, 2007. http://web.archive.org/web/20070225125621/http%3A//www.tarleton.edu/%7Etxjanr/2003issue/article3.pdf. 
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  9. ^ Honey Research Unit
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