Flavonoids (or bioflavonoids; from the Latin word ''flavus'', meaning yellow, their color in nature) are a class 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 of ...

secondary metabolite Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by any lifeform, e.g. bacteria, fungi, animals, or plants, which are not directly involved in the norm ...

s found in plants, and thus commonly consumed in the diets of humans. Chemically, flavonoids have the general structure of a 15-carbon skeleton, which consists of two

phenyl In organic chemistry, the phenyl group, or phenyl ring, is a cyclic group of atoms with the formula C6 H5, and is often represented by the symbol Ph. Phenyl group is closely related to benzene and can be viewed as a benzene ring, minus a hydrogen ...

rings (A and B) and a

heterocyclic ring A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different chemical element, elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis ...

(C, the ring containing the embedded

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...

). This carbon structure can be abbreviated C6-C3-C6. According to the

IUPAC The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...

nomenclature, they can be classified into: *flavonoids or bioflavonoids *

isoflavonoid Isoflavonoids are a class of flavonoid phenolic compounds, many of which are biologically active. Isoflavonoids and their derivatives are sometimes referred to as phytoestrogens, as many isoflavonoid compounds have biological effects via the estro ...

s, derived from 3-phenyl chromen-4-one (3-phenyl-1,4-

benzopyrone Benzopyrone may refer to either of two ketone derivatives of benzopyran which constitute the core skeleton of many flavonoid compounds: *Chromone (1-benzopyran-4-one) *Coumarin (1-benzopyran-2-one) Certain simple benzopyrones have clinical medical ...

) structure *

neoflavonoids Neoflavonoids are a class of polyphenolic compounds. While flavonoids (in the narrow sense) have the 2-phenylchromen-4-one backbone, neoflavonoids have the 4-phenylchromen backbone with no hydroxyl group substitution at position 2. Types Neoflavo ...

, derived from 4-phenyl

coumarine Coumarin () or 2''H''-chromen-2-one is an aromatic organic chemical compound with formula . Its molecule can be described as a benzene molecule with two adjacent hydrogen atoms replaced by a lactone-like chain , forming a second six-membered h ...

(4-phenyl-1,2-

) structure The three flavonoid classes above are all

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...

-containing compounds and as such,

anthoxanthin Anthoxanthins ( flavones and flavonols)Isolation of a UDP-glucose: Flavonoid 5-O-glucosyltransferase gene and expression analysis of anthocyanin biosynthetic genes in herbaceous peony (Paeonia lactiflora Pall.). Da Qiu Zhao, Chen Xia Han, Jin Tao ...

s (

flavone Flavone is an organic compound with the formula . A white solid, flavone is a derivative of chromone with a phenyl (Ph) substituent adjacent to the ether group. The compound is of little direct practical importance, but susbstituted derivatives, t ...

s and

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 "a ...

s). 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. The three cycles or heterocycles in the flavonoid backbone are generally called ring A, B, and C. Ring A usually shows a

phloroglucinol Phloroglucinol is an organic compound with the formula C6H3(OH)3. It is a colorless solid. It is used in the synthesis of pharmaceuticals and explosives. Phloroglucinol is one of three isomeric benzenetriols. The other two isomers are hydroxyqu ...

substitution pattern.

History

In the 1930s,

Albert Szent-Györgyi Albert Imre Szent-Györgyi de Nagyrápolt ( hu, nagyrápolti Szent-Györgyi Albert Imre; September 16, 1893 – October 22, 1986) was a Hungarian biochemist who won the Nobel Prize in Physiology or Medicine in 1937. He is credited with fi ...

and other scientists discovered that

Vitamin C Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...

alone was not as effective at preventing

scurvy Scurvy is a disease resulting from a lack of vitamin C (ascorbic acid). Early symptoms of deficiency include weakness, feeling tired and sore arms and legs. Without treatment, decreased red blood cells, gum disease, changes to hair, and bleeding ...

as the crude yellow extract from oranges, lemons or paprika. They attributed the increased activity of this extract to the other substances in this mixture, which they referred to as "citrin" (referring to citrus) or "Vitamin P" (a reference to its effect on reducing the permeability of

capillaries A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...

). The substances in question (

hesperidin Hesperidin is a flavanone glycoside found in citrus fruits. Its aglycone form is called hesperetin. Its name is derived from the word "hesperidium", for fruit produced by citrus trees. Hesperidin was first isolated in 1828 by French chemist M. ...

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 proper ...

, hesperidin methyl chalcone and

neohesperidin Neohesperidin is a flavanone glycoside found in citrus fruits. It is the 7-O-neohesperidose derivative of hesperetin, which in turn is the 4'-methoxy derivative of eriodictyol Eriodictyol is a bitter-masking flavanone, a flavonoid extracted from ...

) were however later shown not to fulfil the criteria of a vitamin, so that this term is now obsolete.

Biosynthesis

Flavonoids are secondary metabolites synthesized mainly by plants. The general structure of flavonoids is a 15-carbon skeleton, containing 2 benzene rings connected by a 3-carbon linking chain. Therefore, they are depicted as C6-C3-C6 compounds. Depending on the chemical structure, degree of oxidation, and unsaturation of the linking chain (C3), flavonoids can be classified into different groups, such as anthocyanidins, chalcones, flavonols, flavanones, flavan-3-ols, flavanonols, flavones, and isoflavonoids. Furthermore, flavonoids can be found in plants in glycoside-bound and free aglycone forms. The glycoside-bound form is the most common flavone and flavonol form consumed in the diet.

Functions of flavonoids in plants

Flavonoids are widely distributed in plants, fulfilling many functions. They are the most important

plant pigment Biological pigments, also known simply as pigments or biochromes, are substances produced by living organisms that have a color resulting from selective color absorption. Biological pigments include plant pigments and flower pigments. Many biol ...

s for flower coloration, producing yellow or red/blue pigmentation in petals designed to attract

pollinator A pollinator is an animal that moves pollen from the male anther of a flower to the female stigma of a flower. This helps to bring about fertilization of the ovules in the flower by the male gametes from the pollen grains. Insects are the maj ...

animals. In higher plants, they are involved in UV filtration, symbiotic nitrogen fixation, and floral pigmentation. They may also act as chemical messengers, physiological regulators, and cell cycle inhibitors. Flavonoids secreted by the root of their host plant help ''

Rhizobia Rhizobia are diazotrophic bacteria that fix nitrogen after becoming established inside the root nodules of legumes (Fabaceae). To express genes for nitrogen fixation, rhizobia require a plant host; they cannot independently fix nitrogen. In gene ...

'' in the infection stage of their

symbiotic Symbiosis (from Greek , , "living together", from , , "together", and , bíōsis, "living") is any type of a close and long-term biological interaction between two different biological organisms, be it mutualistic, commensalistic, or parasit ...

relationship with legumes like peas, beans, clover, and soy. Rhizobia living in soil are able to sense the flavonoids and this triggers the secretion of

Nod factor Nod factors (nodulation factors or NF), are signaling molecules produced by soil bacteria known as rhizobia in response to flavonoid exudation from plants under nitrogen limited conditions. Nod factors initiate the establishment of a symbiotic re ...

s, which in turn are recognized by the host plant and can lead to root hair deformation and several cellular responses such as ion fluxes and the formation of a

root nodule Root nodules are found on the roots of plants, primarily legumes, that form a symbiosis with nitrogen-fixing bacteria. Under nitrogen-limiting conditions, capable plants form a symbiotic relationship with a host-specific strain of bacteria known a ...

. In addition, some flavonoids have inhibitory activity against organisms that cause plant diseases, e.g. ''Fusarium oxysporum''.

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):

Anthocyanidins

Anthocyanidin Anthocyanidins are common plant pigments, the sugar-free counterparts of anthocyanins. They are based on the flavylium cation, an oxonium ion, with various groups substituted for its hydrogen atoms. They generally change color from red through ...

s are 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 ...

s of

anthocyanin Anthocyanins (), also called anthocyans, are water-soluble vacuolar pigments that, depending on their pH, may appear red, purple, blue, or black. In 1835, the German pharmacist Ludwig Clamor Marquart gave the name Anthokyan to a chemical compo ...

s; they use the

flavylium Pyrylium is a cation (positive ion) with formula , consisting of a six-membered ring of five carbon atoms, each with one hydrogen atom, and one positively charged oxygen atom. The bonds in the ring are conjugated as in benzene, giving it an aroma ...

(2-phenylchromenylium) ion skeleton. *:Examples:

Cyanidin Cyanidin is a natural organic compound. It is a particular type of anthocyanidin (glycoside version called anthocyanins). It is a pigment found in many red berries including grapes, bilberry, blackberry, blueberry, cherry, chokeberry, cranb ...

Delphinidin Delphinidin (also delphinidine) is an anthocyanidin, a primary plant pigment, and also an antioxidant. Delphinidin gives blue hues to flowers in the genera ''Viola'' and ''Delphinium''. It also gives the blue-red color of the grape that produces ...

Malvidin Malvidin is an O-methylated anthocyanidin, the 3',5'-methoxy derivative of delphinidin. As a primary plant pigment, its glycosides are highly abundant in nature. Natural occurrences Malvidin is responsible for the blue color found in petals of ...

Pelargonidin Pelargonidin is an anthocyanidin, a type of plant pigment producing a characteristic orange color used in food and industrial dyes. Natural occurrences Presence in flowers Pelargonidin can be found in red geraniums (Geraniaceae). It is the p ...

Peonidin Peonidin is an O-methylated anthocyanidin derived from Cyanidin, and a primary plant pigment. Peonidin gives purplish-red hues to flowers such as the peony, from which it takes its name, and roses. It is also present in some blue flowers, such as ...

Petunidin Petunidin (Pt), like Europinidin and Malvidin, is derived from Delphinidin and is an O-methylated anthocyanidin of the 3-hydroxy type. It is a natural organic compound, a dark-red or purple water-soluble pigment found in many redberries including ...

Anthoxanthins

Anthoxanthin Anthoxanthins ( flavones and flavonols)Isolation of a UDP-glucose: Flavonoid 5-O-glucosyltransferase gene and expression analysis of anthocyanin biosynthetic genes in herbaceous peony (Paeonia lactiflora Pall.). Da Qiu Zhao, Chen Xia Han, Jin Tao ...

s are divided into two groups:

Flavanones

Flavanone The flavanones, a type of flavonoids, are various aromatic, colorless ketones derived from flavone that often occur in plants as glycosides. List of flavanones * Blumeatin * Butin * Eriodictyol * Hesperetin * Hesperidin * Homoeriodictyol * Iso ...

Flavanonols

Flavanonol The flavanonols (with two "o"s a.k.a. 3-hydroxyflavanone or 2,3-dihydroflavonol) are a class of flavonoids that use the 3-hydroxy-2,3-dihydro-2-phenylchromen-4-one (IUPAC name) backbone. Some examples include: * Taxifolin (or Dihydroquercetin) * ...

Flavans

Include

flavan-3-ol Flavan-3-ols (sometimes referred to as flavanols) are a subgroup of flavonoids. They are derivatives of flavans that possess a 2-phenyl-3,4-dihydro-2''H''-chromen-3-ol skeleton. Flavan-3-ols are structurally diverse and include a range of compo ...

s (flavanols),

flavan-4-ol The flavan-4-ols (3-deoxyflavonoids) are flavone-derived alcohols and a family of flavonoids. Flavan-4-ols are colorless precursor compounds that polymerize to form red phlobaphene pigments. They can be found in the sorghum. Glycosides (abacopterin ...

s and

flavan-3,4-diol Leucoanthocyanidin (flavan-3,4-diols) are colorless chemical compounds related to anthocyanidins and anthocyanins. Leucoanthocyanins can be found in ''Anadenanthera peregrina'' and in several species of ''Nepenthes'' including ''Nepenthes burbidgea ...

s. *

Flavan-3-ols Flavan-3-ols (sometimes referred to as flavanols) are a subgroup of flavonoids. They are derivatives of flavans that possess a 2-phenyl-3,4-dihydro-2''H''-chromen-3-ol skeleton. Flavan-3-ols are structurally diverse and include a range of compo ...

(flavanols) ** Flavan-''3-ols'' use the 2-phenyl-3,4-dihydro-2''H''-chromen-''3-ol'' skeleton *:Examples:

Catechin Catechin is a flavan-3-ol, a type of secondary metabolite providing antioxidant roles in plants. It belongs to the subgroup of polyphenols called flavonoids. The name of the catechin chemical family derives from ''catechu'', which is the tannic ...

(C),

Gallocatechin Gallocatechol or gallocatechin (GC) is a flavan-3-ol, a type of chemical compound including catechin, with the gallate residue being in an Cis-trans isomerism, isomeric trans position. This compound possesses two epimers. The most common, (+)-gal ...

(GC),

Catechin 3-gallate Catechin is a flavan-3-ol, a type of secondary metabolite providing antioxidant roles in plants. It belongs to the subgroup of polyphenols called flavonoids. The name of the catechin chemical family derives from ''catechu'', which is the tanni ...

(Cg),

Gallocatechin 3-gallate Gallocatechol or gallocatechin (GC) is a flavan-3-ol, a type of chemical compound including catechin, with the gallate residue being in an isomeric trans position. This compound possesses two epimers. The most common, (+)-gallocatechin (GC), CAS ...

(GCg),

Epicatechin Catechin is a flavan-3-ol, a type of secondary metabolite providing antioxidant roles in plants. It belongs to the subgroup of polyphenols called flavonoids. The name of the catechin chemical family derives from ''catechu'', which is the tannic ...

s (

(EC)),

Epigallocatechin Gallocatechol or gallocatechin (GC) is a flavan-3-ol, a type of chemical compound including catechin, with the gallate residue being in an isomeric trans position. This compound possesses two epimers. The most common, (+)-gallocatechin (GC), CAS ...

(EGC),

Epicatechin 3-gallate Epicatechin gallate (ECG) is a flavan-3-ol, a type of flavonoid, present in green tea. It is also reported in buckwheat and in grape. The tea component epicatechin gallate is being researched because in vitro experiments showed it can reverse me ...

(ECg), Epigallocatechin 3-gallate (EGCg) **

Theaflavin Theaflavin (TF) and its derivatives, known collectively as ''theaflavins'', are antioxidant polyphenols that are formed from the condensation of flavan-3-ols in tea leaves during the enzymatic oxidation (sometimes erroneously referred to as ferment ...

*:Examples:

Theaflavin-3-gallate Theaflavin-3-gallate is a theaflavin derivative. It can be found in abundance in black tea and is produced during fermentation. It has been studied as a cancer-fighting chemical when combined with cisplatin against ovarian cancer cells. Consuming ...

, Theaflavin-3'-gallate,

Theaflavin-3,3'-digallate Theaflavin digallate (TFDG) is an antioxidant natural phenol found in black tea, and a theaflavin derivative. Health * TFDG is a scavenger of superoxide ''in vitro'', even more so than EGCG. * Tea polyphenols including TFDG reduce angiogenesis, ...

Thearubigin Thearubigins are polymeric polyphenols that are formed during the enzymatic oxidation and condensation of two gallocatechins (epigallocatechin and epigallocatechin gallate) with the participation of polyphenol oxidases during the fermentation react ...

Proanthocyanidins Proanthocyanidins are a class of polyphenols found in many plants, such as cranberry, blueberry, and grape seeds. Chemically, they are oligomeric flavonoids. Many are oligomers of catechin and epicatechin and their gallic acid esters. More complex ...

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

Isoflavonoids

Isoflavonoid Isoflavonoids are a class of flavonoid phenolic compounds, many of which are biologically active. Isoflavonoids and their derivatives are sometimes referred to as phytoestrogens, as many isoflavonoid compounds have biological effects via the estro ...

s **

Isoflavone Isoflavones are substituted derivatives of isoflavone, a type of naturally occurring isoflavonoids, many of which act as phytoestrogens in mammals. Isoflavones are produced almost exclusively by the members of the bean family, Fabaceae (Leguminosae ...

s use the 3-phenylchromen-''4-one'' skeleton (with no hydroxyl group substitution on carbon at position 2) *:Examples:

Genistein Genistein (C15H10O5) is a naturally occurring compound that structurally belongs to a class of compounds known as isoflavones. It is described as an angiogenesis inhibitor and a phytoestrogen. It was first isolated in 1899 from the dyer's bro ...

Daidzein Daidzein (7-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one) is a naturally occurring compound found exclusively in soybeans and other legumes and structurally belongs to a class of compounds known as isoflavones. Daidzein and other isoflavones a ...

Glycitein Glycitein is an O-methylated isoflavone which accounts for 5-10% of the total isoflavones in soy food products. Glycitein is a phytoestrogen A phytoestrogen is a plant-derived xenoestrogen (see estrogen) not generated within the endocrine sy ...

Isoflavane Isoflavanes are a class of isoflavonoids, which are themselves types of polyphenolic compounds. They have the 3-phenylchroman (isoflavan, CAS number: 4737-26-2, molecular formula: C15H14O, exact mass: 210.1044646 u) backbone. Examples * Equol S ...

s **

Isoflavandiol Isoflavanes are a class of isoflavonoids, which are themselves types of polyphenolic compounds. They have the 3-phenylchroman (isoflavan, CAS number: 4737-26-2, molecular formula: C15H14O, exact mass: 210.1044646 u) backbone. Examples * Equol S ...

s ** Isoflavenes **

Coumestan Coumestan is a heterocyclic organic compound. Coumestan forms the central core of a variety of natural compounds known collectively as coumestans. Coumestans are oxidation products of pterocarpan that are similar to coumarin. Coumestans, includ ...

s **

Pterocarpan Pterocarpans are derivatives of isoflavonoids found in the family Fabaceae. It is a group of compounds which can be described as benzo-pyrano-furano-benzenes (i.e. 6''H''- enzofuro ,2-chromene skeleton) which can be formed by coupling of the B rin ...

Dietary sources

Flavonoids (specifically flavanoids such as the

catechins Flavan-3-ols (sometimes referred to as flavanols) are a subgroup of flavonoids. They are derivatives of flavans that possess a 2-phenyl-3,4-dihydro-2''H''-chromen-3-ol skeleton. Flavan-3-ols are structurally diverse and include a range of compo ...

) are "the most common group of

ic compounds in the human diet and are found ubiquitously in plants". Flavonols, the original bioflavonoids such as

quercetin Quercetin is a plant flavonol from the flavonoid group of polyphenols. 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 a ...

, are also found ubiquitously, but in lesser quantities. The widespread distribution of flavonoids, their variety and their relatively low

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

compared to other active plant compounds (for instance

alkaloids Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar st ...

) mean that many animals, including

humans Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

, ingest significant quantities in their diet. Foods with a high flavonoid content include

parsley Parsley, or garden parsley (''Petroselinum crispum'') is a species of flowering plant in the family Apiaceae that is native to the central and eastern Mediterranean region (Sardinia, Lebanon, Israel, Cyprus, Turkey, southern Italy, Greece, Por ...

,USDA’s Database on the Flavonoid Content
/ref>

onion An onion (''Allium cepa'' L., from Latin ''cepa'' meaning "onion"), also known as the bulb onion or common onion, is a vegetable that is the most widely cultivated species of the genus ''Allium''. The shallot is a botanical variety of the onion ...

blueberries Blueberries are a widely distributed and widespread group of perennial flowering plants with blue or purple berries. They are classified in the section ''Cyanococcus'' within the genus ''Vaccinium''. ''Vaccinium'' also includes cranberries, bi ...

and other

berries A berry is a small, pulpy, and often edible fruit. Typically, berries are juicy, rounded, brightly colored, sweet, sour or tart, and do not have a stone or pit, although many pips or seeds may be present. Common examples are strawberries, raspb ...

black tea Black tea, also translated to red tea in various East Asian languages, is a type of tea that is more oxidized than oolong, yellow, white and green teas. Black tea is generally stronger in flavour than other teas. All five types are made from ...

green tea Green tea is a type of tea that is made from '' Camellia sinensis'' leaves and buds that have not undergone the same withering and oxidation process which is used to make oolong teas and black teas. Green tea originated in China, and since the ...

and

oolong tea Oolong (, ; (''wūlóngchá'', "dark dragon" tea)) is a traditional semi-oxidized Chinese tea (''Camellia sinensis)'' produced through a process including withering the plant under strong sun and oxidation before curling and twisting.Zhongguo ...

banana A banana is an elongated, edible fruit – botanically a berry – produced by several kinds of large herbaceous flowering plants in the genus ''Musa''. In some countries, bananas used for cooking may be called "plantains", distinguis ...

s, all

citrus ''Citrus'' is a genus of flowering plant, flowering trees and shrubs in the rue family, Rutaceae. Plants in the genus produce citrus fruits, including important crops such as Orange (fruit), oranges, Lemon, lemons, grapefruits, pomelos, and lim ...

fruits, ''

Ginkgo biloba ''Ginkgo biloba'', commonly known as ginkgo or gingko ( ), also known as the maidenhair tree, is a species of tree native to China. It is the last living species in the order Ginkgoales, which first appeared over 290 million years ago. Fossils ...

'',

red wine Red wine is a type of wine made from dark-colored grape varieties. The color of the wine can range from intense violet, typical of young wines, through to brick red for mature wines and brown for older red wines. The juice from most purple grap ...

, sea-buckthorns,

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 '' Fago ...

, and dark chocolate with a

cocoa Cocoa may refer to: Chocolate * Chocolate * ''Theobroma cacao'', the cocoa tree * Cocoa bean, seed of ''Theobroma cacao'' * Chocolate liquor, or cocoa liquor, pure, liquid chocolate extracted from the cocoa bean, including both cocoa butter and ...

content of 70% or greater.

Parsley

Parsley Parsley, or garden parsley (''Petroselinum crispum'') is a species of flowering plant in the family Apiaceae that is native to the central and eastern Mediterranean region (Sardinia, Lebanon, Israel, Cyprus, Turkey, southern Italy, Greece, Por ...

, both fresh and dried, contains

flavones Flavones (from Latin ''flavus'' "yellow") are a class of flavonoids based on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one) (as shown in the first image of this article). Flavones are common in foods, mainly from spices, and ...

Blueberries

Blueberries Blueberries are a widely distributed and widespread group of perennial flowering plants with blue or purple berries. They are classified in the section ''Cyanococcus'' within the genus ''Vaccinium''. ''Vaccinium'' also includes cranberries, bi ...

are a dietary source of

anthocyanidins Anthocyanidins are common plant pigments, the sugar-free counterparts of anthocyanins. They are based on the flavylium cation, an oxonium ion, with various groups substituted for its hydrogen atoms. They generally change color from red through ...

Black tea

Black tea Black tea, also translated to red tea in various East Asian languages, is a type of tea that is more oxidized than oolong, yellow, white and green teas. Black tea is generally stronger in flavour than other teas. All five types are made from ...

is a rich source of dietary

flavan-3-ols Flavan-3-ols (sometimes referred to as flavanols) are a subgroup of flavonoids. They are derivatives of flavans that possess a 2-phenyl-3,4-dihydro-2''H''-chromen-3-ol skeleton. Flavan-3-ols are structurally diverse and include a range of compo ...

Citrus

The citrus flavonoids include

(a glycoside of the flavanone

hesperetin Hesperetin is the 4'-methoxy derivative of eriodictyol, a flavanone. Hesperetin's 7-O-glycoside, hesperidin, is a naturally occurring flavanon-glycoside, the main flavonoid in lemons and sweet oranges. Hesperetin (and naringenin, the parent flavan ...

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 d ...

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 pla ...

(two

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 glycosides. ...

s of the flavonol

), and the flavone

tangeritin Tangeretin is an O- polymethoxylated flavone that is found in tangerine and other 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 ...

. The flavonoids are much less concentrated in the

pulp Pulp may refer to: * Pulp (fruit), the inner flesh of fruit Engineering * Dissolving pulp, highly purified cellulose used in fibre and film manufacture * Pulp (paper), the fibrous material used to make paper * Molded pulp, a packaging material * ...

than in the peels (for example, 165 vs. 1156 mg/100g in pulp vs. peel of

satsuma mandarin ''Citrus unshiu'' is a semi-seedless and easy-peeling citrus species, also known as miyagawa mandarin, unshu mikan, cold hardy mandarin, satsuma mandarin, satsuma orange, naartjie, and tangerine. ''Citrus unshiu'' was named after Unshu (Wenzho ...

, and 164 vis-à-vis 804 mg/100g in pulp vs. peel of

clementine A clementine (''Citrus × clementina'') is a tangor, a citrus fruit hybrid between a willowleaf mandarin orange ( ''C.'' × ''deliciosa'') and a sweet orange (''C. × sinensis''), named in honor of Clément Rodier, a French missionary who fir ...

Wine

Cocoa

Flavonoids exist naturally in

, but because they can be bitter, they are often removed from

chocolate Chocolate is a food made from roasted and ground cacao seed kernels that is available as a liquid, solid, or paste, either on its own or as a flavoring agent in other foods. Cacao has been consumed in some form since at least the Olmec civ ...

, even dark chocolate. Although flavonoids are present in milk chocolate, milk may interfere with their absorption; however this conclusion has been questioned.

Peanut

Peanut The peanut (''Arachis hypogaea''), also known as the groundnut, goober (US), pindar (US) or monkey nut (UK), is a legume crop grown mainly for its edible Seed, seeds. It is widely grown in the tropics and subtropics, important to both small ...

(red) skin contains significant polyphenol content, including flavonoids. Unit: mg/100g

Dietary intake

Food composition data Food composition data (FCD) are detailed sets of information on the nutritionally important components of foods and provide values for energy and nutrients including protein, carbohydrates, fat, vitamins and minerals and for other important food com ...

for flavonoids were provided by the

USDA The United States Department of Agriculture (USDA) is the federal executive department responsible for developing and executing federal laws related to farming, forestry, rural economic development, and food. It aims to meet the needs of com ...

database on flavonoids. In the United States

NHANES The National Health and Nutrition Examination Survey (NHANES) is a survey research program conducted by the National Center for Health Statistics (NCHS) to assess the health and nutritional status of adults and children in the United States, and to ...

survey, mean flavonoid intake was 190 mg/d in adults, with

s as the main contributor. In the

European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...

, based on data from

EFSA The European Food Safety Authority (EFSA) is the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002, ...

, mean flavonoid intake was 140 mg/d, although there were considerable differences among individual countries. The main type of flavonoids consumed in the EU and USA were flavan-3-ols (80% for USA adults), mainly from tea or cocoa in chocolate, while intake of other flavonoids was considerably lower.

Research

Neither the United States

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 ...

(FDA) nor the

European Food Safety Authority The European Food Safety Authority (EFSA) is the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002, ...

(EFSA) has approved any

health claim A health claim on a food label and in food marketing is a claim by a manufacturer of food products that their food will reduce the risk of developing a disease or condition. For example, it is claimed by the manufacturers of oat cereals that oat ...

for flavonoids or approved any flavonoids as

prescription drug A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The rea ...

s. The U.S. FDA has warned numerous dietary supplement companies about illegal advertising and misleading health claims.

Metabolism and excretion

Flavonoids are poorly absorbed in the human body (less than 5%), then are quickly metabolized into smaller fragments with unknown properties, and rapidly excreted. Flavonoids have negligible antioxidant activity in the body, and the increase in antioxidant capacity of blood seen after consumption of flavonoid-rich foods is not caused directly by flavonoids, but by production of

uric acid Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of ...

resulting from flavonoid

depolymerization Depolymerization (or depolymerisation) is the process of converting a polymer into a monomer or a mixture of monomers. This process is driven by an increase in entropy. Ceiling temperature The tendency of polymers to depolymerize is indicated by ...

and

excretion Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...

. Microbial metabolism is a major contributor to the overall metabolism of dietary flavonoids. The effect of habitual flavonoid intake on the human gut microbiome is unknown.

Inflammation

Inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

has been implicated as a possible origin of numerous local and systemic diseases, such as

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

cardiovascular disorders Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...

diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

, and

celiac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barl ...

. There is no clinical evidence that dietary flavonoids affect any of these diseases.

Cancer

Clinical studies Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

investigating the relationship between flavonoid consumption and cancer prevention or development are conflicting for most types of cancer, probably because most human studies have weak designs, such as a small

sample size Sample size determination is the act of choosing the number of observations or Replication (statistics), replicates to include in a statistical sample. The sample size is an important feature of any empirical study in which the goal is to make stat ...

. There is little evidence to indicate that dietary flavonoids affect human cancer risk in general, but

observational studies In fields such as epidemiology, social sciences, psychology and statistics, an observational study draws inferences from a sample (statistics), sample to a statistical population, population where the dependent and independent variables, independ ...

and

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

s on hormone-dependent cancers (breast and prostate) have shown benefits. A recent review has suggested that dietary intake of flavonoids is associated with a reduced risk of different types of cancer, including gastric, breast, prostate, and colorectal cancer.

Cardiovascular diseases

Although no significant association has been found between flavan-3-ol intake and cardiovascular disease mortality, clinical trials have shown improved endothelial function and reduced

blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...

(with a few studies showing inconsistent results). Reviews of

cohort studies A cohort study is a particular form of longitudinal study that samples a cohort (a group of people who share a defining characteristic, typically those who experienced a common event in a selected period, such as birth or graduation), performing ...

in 2013 found that the studies had too many limitations to determine a possible relationship between increased flavonoid intake and decreased risk of cardiovascular disease, although a trend for an inverse relationship existed.

''In vitro''

Laboratory studies on isolated cells or

cell culture Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This te ...

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

indicate that flavonoids may selectively inhibit

kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...

s, but

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

results could differ because of low

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%. H ...

Synthesis, detection, quantification, and semi-synthetic alterations

Color spectrum

Flavonoid synthesis in plants is induced by light color spectrums at both high and low energy radiations. Low energy radiations are accepted by

phytochrome Phytochromes are a class of photoreceptor in plants, bacteria and fungi used to detect light. They are sensitive to light in the red and far-red region of the visible spectrum and can be classed as either Type I, which are activated by far-re ...

, while high energy radiations are accepted by

carotenoid Carotenoids (), also called tetraterpenoids, are yellow, orange, and red organic compound, organic pigments that are produced by plants and algae, as well as several bacteria, and Fungus, fungi. Carotenoids give the characteristic color to pumpki ...

flavins Flavins (from Latin ''flavus'', "yellow") are organic compounds, like their base, pteridine. They are formed by the tricyclic heterocycle isoalloxazine. The biochemical source is the vitamin riboflavin. The flavin moiety is often attached with a ...

cryptochrome Cryptochromes (from the Greek κρυπτός χρώμα, "hidden colour") are a class of flavoproteins found in plants and animals that are sensitive to blue light. They are involved in the circadian rhythms and the sensing of magnetic fields i ...

s in addition to phytochromes. The photomorphogenic process of phytochrome-mediated flavonoid biosynthesis has been observed in ''Amaranthus'',

barley Barley (''Hordeum vulgare''), a member of the grass family, is a major cereal grain grown in temperate climates globally. It was one of the first cultivated grains, particularly in Eurasia as early as 10,000 years ago. Globally 70% of barley pr ...

maize Maize ( ; ''Zea mays'' subsp. ''mays'', from es, maíz after tnq, mahiz), also known as corn (North American and Australian English), is a cereal grain first domesticated by indigenous peoples in southern Mexico about 10,000 years ago. Th ...

, ''

Sorghum ''Sorghum'' () is a genus of about 25 species of flowering plants in the grass family (Poaceae). Some of these species are grown as cereals for human consumption and some in pastures for animals. One species is grown for grain, while many othe ...

'' and

turnip The turnip or white turnip (''Brassica rapa'' subsp. ''rapa'') is a root vegetable commonly grown in temperate climates worldwide for its white, fleshy taproot. The word ''turnip'' is a compound of ''turn'' as in turned/rounded on a lathe and ' ...

. Red light promotes flavonoid synthesis.

Availability through microorganisms

Several recent research articles have demonstrated the efficient production of flavonoid molecules from genetically engineered microorganisms. and the project SynBio4Flav aims to provide a cost-effective alternative to current flavonoid production breaking down their complex

biosynthetic pathway Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

s into standardized specific parts, which can be transferred to engineered microorganisms within Synthetic Microbial Consortia to promote flavonoid assembly through distributed

catalysis Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

Tests for detection

;Shinoda test Four pieces of magnesium filings are added to the ethanolic extract followed by few drops of concentrated

hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid Acid strength is the tendency of an acid, symbol ...

. A pink or red colour indicates the presence of flavonoid. Colours varying from orange to red indicated

s, red to crimson indicated flavonoids, crimson to magenta indicated flavonones. ;Sodium hydroxide test About 5 mg of the compound is dissolved in water, warmed, and filtered. 10% aqueous

sodium hydroxide Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula NaOH. It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly caustic base and alkali ...

is added to 2 ml of this solution. This produces a yellow coloration. A change in color from yellow to colorless on addition of dilute hydrochloric acid is an indication for the presence of flavonoids. ; p-Dimethylaminocinnamaldehyde test A colorimetric assay based upon the reaction of A-rings with the chromogen p-dimethylaminocinnamaldehyde (DMACA) has been developed for flavanoids in beer that can be compared with the

vanillin Vanillin is an organic compound with the molecular formula . It is a phenolic aldehyde. Its functional groups include aldehyde, hydroxyl, and ether. It is the primary component of the extract of the vanilla bean. Synthetic vanillin is now used ...

procedure.

Quantification

Lamaison and Carnet have designed a test for the determination of the total flavonoid content of a sample (AlCI₃ method). After proper mixing of the sample and the reagent, the mixture is incubated for ten minutes at ambient temperature and the absorbance of the solution is read at 440 nm. Flavonoid content is expressed in mg/g of quercetin.

Semi-synthetic alterations

Immobilized ''

Candida antarctica ''Candida antarctica'' is a yeast species in the genus '' Candida''. ''Candida antarctica'' is a source of important industrial enzymes. Immobilized ''Candida antarctica'' lipase can be used to catalyze the regioselective acylation of flavono ...

'' lipase can be used to catalyze the

regioselective In chemistry, regioselectivity is the preference of chemical bonding or breaking in one direction over all other possible directions. It can often apply to which of many possible positions a reagent will affect, such as which proton a strong base ...

acylation In chemistry, acylation (or alkanoylation) is the chemical reaction in which an acyl group () is added to a compound. The compound providing the acyl group is called the acylating agent. Because they form a strong electrophile when treated with ...

of flavonoids.

History

Biosynthesis

Functions of flavonoids in plants

Subgroups

Anthocyanidins

Anthoxanthins

Flavanones

Flavanonols

Flavans

Isoflavonoids

Dietary sources

Parsley

Blueberries

Black tea

Citrus

Wine

Cocoa

Peanut

Dietary intake

Research

Metabolism and excretion

Inflammation

Cancer

Cardiovascular diseases

''In vitro''

Synthesis, detection, quantification, and semi-synthetic alterations

Color spectrum

Availability through microorganisms

Tests for detection

Quantification

Semi-synthetic alterations

See also

References

Further reading

Databases