flavonoid

Molecular structure of the flavone backbone (2-phenyl-1,4-benzopyrone)

Flavonoids (or bioflavonoids), also collectively known as Vitamin P and citrin^[1], are a class of plant secondary metabolites. According to the IUPAC nomenclature,^[2] they can be classified into:

• flavonoids, derived from 2-phenylchromen-4-one (2-phenyl-1,4-benzopyrone) structure (examples: quercetin, rutin).
• isoflavonoids, derived from 3-phenylchromen-4-one (3-phenyl-1,4-benzopyrone) structure
• neoflavonoids, derived from 4-phenylcoumarine (4-phenyl-1,2-benzopyrone) structure.

The three flavonoid classes above are all ketone-containing compounds, and as such, are flavonoids and flavonols. This class was the first to be termed "bioflavonoids." The terms flavonoid and bioflavonoid have also been more loosely used to describe non-ketone polyhydroxy polyphenol compounds which are more specifically termed flavanoids, flavan-3-ols, or catechins (although catechins are actually a subgroup of flavanoids).

Flavonoids (both flavonols and flavanols) are most commonly known for their antioxidant activity.

Flavonoids (specifically flavanoids such as the catechins) are "the most common group of polyphenolic compounds in the human diet and are found ubiquitously in plants".^[3] Flavonols, the original bioflavonoids such as quercetin, are also found ubiquitously, but in lesser quantities. Both sets of compounds have evidence of health-modulating effects in animals which eat them.

Biosynthesis

Flavonoids are synthesized by the phenylpropanoid metabolic pathway in which the amino acid phenylalanine is used to produce 4-coumaroyl-CoA^[4]. This can be combined with malonyl-CoA to yield the true backbone of flavonoids, a group of compounds called chalcones, which contain two phenyl rings (see polyphenols). Conjugate ring-closure of chalcones results in the familiar form of flavonoids, the three-ringed structure of a flavone. The metabolic pathway continues through a series of enzymatic modifications to yield flavanones → dihydroflavonols → anthocyanins. Along this pathway, many products can be formed, including the flavonols, flavan-3-ols, proanthocyanidins (tannins) and a host of other various polyphenolics.

Biological roles

Flavonoids are widely distributed in plants fulfilling many functions.

Flavonoids are the most important pigments for flower coloration producing yellow or red/blue pigmentation in petals. This give an easy way to identify member of a phylum. Those colors are a mean to attract pollinator animals.

They also protect plants from attacks by microbes and insects.

The widespread distribution of flavonoids, their variety and their relatively low toxicity compared to other active plant compounds (for instance alkaloids) mean that many animals, including humans, ingest significant quantities in their diet. Flavonoids have been referred to as "nature's biological response modifiers" because of strong experimental evidence of their inherent ability to modify the body's reaction to allergens, viruses, and carcinogens. They show anti-allergic, anti-inflammatory^[5] , anti-microbial^[6] and anti-cancer activity.

Consumers and food manufacturers have become interested in flavonoids for their medicinal properties, especially their potential role in the prevention of cancers and cardiovascular disease. The beneficial effects of fruit, vegetables, and tea or even red wine have been attributed to flavonoid compounds rather than to known nutrients and vitamins^[7].

Health benefits aside from antioxidant values

In 2007, research conducted at the Linus Pauling Institute and published in Free Radical Biology and Medicine indicates that inside the human body, flavonoids themselves are of little or no direct antioxidant value ^[8]. Body conditions prove to be unlike controlled test tube conditions, and the flavonoids are poorly absorbed (less than 5%), with most of what is absorbed being quickly metabolized and excreted.

The huge increase in antioxidant capacity of blood seen after the consumption of flavonoid-rich foods is not caused directly by the flavonoids themselves, but most likely is due to increased uric acid levels that result from expelling flavonoids from the body.^[9] According to Frei, "we can now follow the activity of flavonoids in the body, and one thing that is clear is that the body sees them as foreign compounds and is trying to get rid of them."

Cancer

The process of gearing up to get rid of unwanted compounds is inducing so-called Phase II enzymes that also help eliminate mutagens and carcinogens, and therefore may be of value in cancer prevention. Flavonoids could also induce mechanisms that help kill cancer cells and inhibit tumor invasion."^[9] UCLA cancer researchers have found that study participants who ate foods containing certain flavonoids seemed to be protected from developing lung cancer. Dr. Zuo-Feng Zhang, of the UCLA's Jonsson Cancer Center and a professor of public health and epidemiology at the UCLA School of Public Health said the flavonoids that appeared to be the most protective included catechin, found in strawberries and green and black teas; kaempferol, found in brussel sprouts and apples; and quercetin, found in beans, onions and apples.^[10]

Their research also indicated that only small amounts of flavonoids are necessary to see these medical benefits. Taking large dietary supplements provides no extra benefit and may pose some risks.^[9]

Diarrhea

A study done at Children's Hospital & Research Center Oakland, in collaboration with scientists at Heinrich Heine University in Germany, has shown that epicatechin, quercetin and luteolin can inhibit the development of fluids that result in diarrhea by targeting the intestinal cystic fibrosis transmembrane conductance regulator Cl– transport inhibiting cAMP-stimulated Cl– secretion in the intestine.^[11]

Important flavonoids

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Quercetin

Quercetin

Quercetin is a flavonoid and, to be more specific, a flavonol. It 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. It may also help to prevent some types of cancer, however currently there is more research needed in this area.

Epicatechin

Epicatechin (EC)

Epicatechin improves blood flow and thus seems good for cardiac health. Cocoa, the major ingredient of dark chocolate, contains relatively high amounts of epicatechin and has been found to have nearly twice the antioxidant content of red wine and up to three times that of green tea in in-vitro tests.^[12][13] But in the test outlined above it now appears the beneficial antioxidant effects are minimal as the antioxidants are rapidly excreted from the body.

Important dietary sources

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Good sources of flavonoids include all citrus fruits, berries, ginkgo biloba, onions^[14][15], parsley^[16], pulses^[17], tea (especially white and green tea), red wine, seabuckthorn, and dark chocolate (with a cocoa content of seventy percent or greater).

Citrus

Grapefruit, a type of Citrus

The citrus bioflavonoids include hesperidin (a glycoside of the flavanone hesperetin), quercitrin, rutin (two glycosides of the flavonol quercetin), and the flavone tangeritin. In addition to possessing antioxidant activity and an ability to increase intracellular levels of vitamin C, rutin and hesperidin exert beneficial effects on capillary permeability and blood flow. They also exhibit some of the anti-allergy and anti-inflammatory benefits of quercetin. Quercetin can also inhibit reverse transcriptase, part of the replication process of retroviruses.^[18] The therapeutical relevance of this inhibition has not been established. Hydroxyethylrutosides (HER) have been used in the treatment of capillary permeability, easy bruising, hemorrhoids, and varicose veins.

Tea

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Bai Hao Yinzhen from Fuding in Fujian Province, widely considered^{[citation needed]} the best grade of white tea

Green tea flavonoids are potent antioxidant compounds, thought to reduce incidence of cancer and heart disease. The major flavonoids in green tea are the kaempferol and catechins (catechin, epicatechin, epicatechin gallate (ECG), and epigallocatechin gallate (EGCG)).

In producing teas such as oolong tea and black tea, the leaves are allowed to oxidize, during which enzymes present in the tea convert some or all of the catechins to larger molecules^{[citation needed]}. However, green tea is produced by steaming the fresh-cut leaf, which inactivates these enzymes, and oxidation does not significantly occur. White tea is the least processed of teas and is shown^{[citation needed]} to present the highest amount of catechins known to occur in camellia sinensis.

Wine

Grape skins contain significant amounts of flavonoids as well as other polyphenols^[19]. Both red and white wine contain flavonoids; however, since red wine is produced by fermentation in the presence of the grape skins, red wine has been observed to contain higher levels of flavonoids, and other polyphenolics such as resveratrol.

Dark chocolate

Flavonoids exist naturally in cacao, but because they can be bitter, they are often removed from chocolate, even the dark variety^[20].

Subgroups

Over 5000 naturally occurring flavonoids have been characterized from various plants. They have been classified according to their chemical structure, and are usually subdivided into the following subgroups (for further reading see ^[4]):

Flavones

Flavones are divided into four groups:^[21]

Group	Skeleton				Examples
	Description	Functional groups		Structural formula
		3-hydroxyl	2,3-dihydro
Flavone	2-phenylchromen-4-one				Luteolin, Apigenin, Tangeritin
Flavonol or 3-hydroxyflavone	3-hydroxy-2-phenylchromen-4-one				Quercetin, Kaempferol, Myricetin, Fisetin, Isorhamnetin, Pachypodol, Rhamnazin
Flavanone	2,3-dihydro-2-phenylchromen-4-one				Hesperetin, Naringenin, Eriodictyol, Homoeriodictyol
Flavanonol or 3-Hydroxyflavanone or 2,3-dihydroflavonol	3-hydroxy-2,3-dihydro-2-phenylchromen-4-one				Taxifolin (or Dihydroquercetin), Dihydrokaempferol

Isoflavones

• Isoflavones

  Isoflavones use the 3-phenylchromen-4-one skeleton (with no hydroxyl group substitution on carbon at position 2).

  Examples: Genistein, Daidzein, Glycitein

Flavan-3-ols, Flavan-4-ols, Flavan-3,4-diols, and proanthocyanidins

Flavan structure

Derivatives of flavan.

Skeleton	Name
	Flavan-3-ol
	Flavan-4-ol
	Flavan-3,4-diol (leucoanthocyanidin)

• Flavan-3-ols (also known as flavanols) and Proanthocyanidins

  Flavan-3-ols use the 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton.

  Catechins (Catechin (C), Gallocatechin (GC), Catechin 3-gallate (Cg), Gallocatechin 3-gallate (GCg)), Epicatechins (Epicatechin (EC), Epigallocatechin (EGC), Epicatechin 3-gallate (ECg), Epigallocatechin 3-gallate (EGCg))

  Proanthocyanidins are dimers, trimers, oligomers, or polymers of the flavanols.

Anthocyanidins

Flavylium skeleton of anthocyanidins

• Anthocyanidins

  Anthocyanidins are the aglycones of anthocyanins. Anthocyanidins use the flavylium (2-phenylchromenylium) ion skeleton

  Examples: Cyanidin, Delphinidin, Malvidin, Pelargonidin, Peonidin, Petunidin

Availability through microorganisms

A number of recent research articles have demonstrated the efficient production of flavonoid molecules from genetically-engineered microorganisms^[22][23][24].

See also

References

External links

• Instant insight considering the effect of flavonoids on memory and learning from the Royal Society of Chemistry
• USDA Database of Flavonoid content of food (pdf)
• Flavonoids (chemistry)
• Cornell news on Cocoa
• A Dark Chocolate a Day Keeps the Doctor Away
• Antioxidant in Green Tea may fight Alzheimer's-EGCG
• Yamamoto Y, Gaynor RB (January 2001). "Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer". J. Clin. Invest. 107 (2): 135–42. doi:10.1172/JCI11914. PMID 11160126. PMC 199180. http://www.jci.org/cgi/content/full/107/2/135. 
• FLAVO - European Project on Flavonoid Research