Flavonoids (or bioflavonoids; from the Latin word flavus, meaning yellow, their color in nature) are a class of polyphenolic secondary metabolites found in plants. Blackberry, black currant, chokeberry, and red cabbage are examples of plants with rich contents of flavonoids. In plant biology, flavonoids fulfill diverse functions, including attraction of pollinating insects, antioxidant protection against ultraviolet light, deterrence of environmental stresses and pathogens, and regulation of cell growth.
Although commonly consumed in human and animal plant foods and in dietary supplements, flavonoids are not considered to be nutrients or biological antioxidants essential to body functions, and have no established effects on human health or prevention of diseases.
Chemically, flavonoids have the general structure of a 15-carbon skeleton consisting of two phenyl rings (A and B) and a heterocyclic ring (C, the ring containing the embedded oxygen). This carbon structure can be abbreviated C6-C3-C6. According to the IUPAC nomenclature, they can be classified into flavonoids or bioflavonoids, isoflavonoids, derived from 3-phenylchromen-4-one (3-phenyl-1,4-benzopyrone) structure, and neoflavonoids, derived from 4-phenylcoumarin (4-phenyl-1,2-benzopyrone) structure.
As ketone-containing compounds, the three flavonoid classes are grouped as anthoxanthins (flavones and flavonols). so that the term "vitamin P" is now obsolete.
<gallery>
File:Flavon.svg|Molecular structure of the flavone backbone (2-phenyl-1,4-benzopyrone)
File:Isoflavan.svg|Isoflavan structure
File:4-phenylcoumarin.svg|Neoflavonoids structure
</gallery>
Biosynthesis
Flavonoids are secondary metabolites synthesized mainly by plants. The general structure of flavonoids is a fifteen-carbon skeleton, containing two benzene rings connected by a three-carbon linking chain.
Subgroups
Flavonoids have been classified according to their chemical structure, and are usually subdivided into the following subgroups:
Anthocyanidins
thumb|right|Flavylium skeleton of anthocyanidins
Anthocyanidins are the aglycones of anthocyanins; they use the flavylium (2-phenylchromenylium) ion skeleton.
:{| class="wikitable"
!rowspan=3|Group
!colspan=4|Skeleton
!rowspan=3|Examples
|-
!rowspan=2|Description
!colspan=2|Functional groups
!rowspan=2|Structural formula
|-
!|3-hydroxyl
!|2,3-dihydro
|-
|style="text-align:center"|Flavones|
|style="text-align:center"|-
|style="text-align:center; font-size:x-large"|✗
|style="text-align:center; font-size:x-large"|✗
||Image:Flavone skeleton colored.svg
||Luteolin, Apigenin, Tangeritin
|-
|style="text-align:center"|Flavonols|<br />or<br />Flavonols|
|style="text-align:center"|--
|style="text-align:center; font-size:x-large"|✓
|style="text-align:center; font-size:x-large"|✗
||Image:Flavonol skeleton colored.svg
||Quercetin, Kaempferol, Myricetin, Fisetin, Galangin, Isorhamnetin, Pachypodol, Rhamnazin, Pyranoflavonols, Furanoflavonols,
|}
Flavanones
Flavanones
{| class="wikitable"
!rowspan=3|Group
!colspan=4|Skeleton
!rowspan=3|Examples
|-
!rowspan=2|Description
!colspan=2|Functional groups
!rowspan=2|Structural formula
|-
!|3-hydroxyl
!|2,3-dihydro
|-
|style="text-align:center"|Flavanones|
|style="text-align:center"|--
|style="text-align:center; font-size:x-large"|✗
|style="text-align:center; font-size:x-large"|✓
||Image:Flavanone skeleton colored.svg
||Hesperetin, Naringenin, Eriodictyol, Homoeriodictyol
|}
Flavanonols
Flavanonols
{| class="wikitable"
!rowspan=3|Group
!colspan=4|Skeleton
!rowspan=3|Examples
|-
!rowspan=2|Description
!colspan=2|Functional groups
!rowspan=2|Structural formula
|-
!|3-hydroxyl
!|2,3-dihydro
|-
|style="text-align:center"|Flavanonols|<br />or<br /><br />or<br />
|style="text-align:center"|---
|style="text-align:center; font-size:x-large"|✓
|style="text-align:center; font-size:x-large"|✓
||Image:Flavanonol skeleton colored.svg
||Taxifolin (or Dihydroquercetin), Dihydrokaempferol
|}
Flavans
thumb|right|Flavan structure
Include flavan-3-ols (flavanols), flavan-4-ols, and flavan-3,4-diols.
{| class="wikitable"
|-
! Skeleton
! Name
<!-- ! header 3 -->
|-
| 100px|Flavan-3-ol
| Flavan-3-ol (flavanol)
<!--|row 1, cell 3 -->
|-
| 100px|Flavan-4ol
| Flavan-4-ol
<!--|row 2, cell 3 -->
|-
| 100px|Flavan-3,4-diol
| Flavan-3,4-diol (leucoanthocyanidin)
<!--|row 3, cell 3 -->
|}
- Flavan-3-ols (flavanols)
- Flavan-3-ols use the 2-phenyl-<u>3,4-dihydro</u>-2H-chromen-3-ol skeleton
- :Examples: catechin (C), gallocatechin (GC), catechin 3-gallate (Cg), gallocatechin 3-gallate (GCg), epicatechins (EC), epigallocatechin (EGC), epicatechin 3-gallate (ECg), epigallocatechin 3-gallate (EGCg)
- Theaflavin
- :Examples: theaflavin-3-gallate, theaflavin-3'-gallate, theaflavin-3,3'-digallate
- Thearubigin
- Proanthocyanidins are dimers, trimers, oligomers, or polymers of the flavanols
Isoflavonoids
- Isoflavonoids
- Isoflavones use the 3-phenylchromen-4-one skeleton (with no hydroxyl group substitution on carbon at position 2)
- :Examples: genistein, daidzein, glycitein
- Isoflavanes
- Isoflavandiols
- Isoflavenes
- Coumestans
- Pterocarpans
Dietary sources
thumb|Parsley is a source of [[flavones]]
thumb|Blueberries are a source of dietary anthocyanins
thumb|Flavonoids are found in [[citrus fruits, including red grapefruit]]
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". Flavonols, the original bioflavonoids such as quercetin, are also found ubiquitously, but in lesser quantities. 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. One study found high flavonoid content in buckwheat.
Citrus flavonoids include hesperidin (a glycoside of the flavanone hesperetin), quercitrin, rutin (two glycosides of quercetin, and the flavone tangeritin.
Peanut (red) skin contains significant polyphenol content, including flavonoids.
Dietary intake
thumb|300px|Adult flavonoid intake (mg per day) in Europe; pie charts indicate the relative consumption of different flavonoid compounds In the [[European Union, based on data from the European Food Safety Authority (EFSA), 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.
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 resulting from flavonoid depolymerization and excretion.
Safety
Likely due to the low bioavailability and rapid metabolism and excretion of flavonoids, there are no safety concerns and no adverse effects associated with high dietary intakes of flavonoids from plant foods.
The FDA has warned numerous dietary supplement and food manufacturers, including Unilever, producer of Lipton tea in the U.S., about illegal advertising and misleading health claims regarding flavonoids, such as that they lower cholesterol or relieve pain.
From 2020 to 2023, the FDA issued 11 warning letters to American manufacturers of flavonoid dietary supplements for false advertising of health claims and illegal misbranding of products.
Research
Antioxidant research
Although flavonoids inhibit free radical activity in vitro, high dietary intakes in humans would be 100 to 1,000 times less than circulating concentrations of dietary and endogenous antioxidants, such as vitamin C, glutathione, and uric acid. cardiovascular disorders, diabetes mellitus, and celiac disease. There is no clinical evidence that dietary flavonoids affect any of these diseases. There is little evidence to indicate that dietary flavonoids affect human cancer risk in general.
In 2013, the EFSA decided to permit health claims that 200 mg/day of cocoa flavanols "help[s] maintain the elasticity of blood vessels." The FDA followed suit in 2023, stating that there is "supportive, but not conclusive" evidence that 200 mg per day of cocoa flavanols can reduce the risk of cardiovascular disease. This is greater than the levels found in typical chocolate bars, which can also contribute to weight gain, potentially harming cardiovascular health.
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, while high energy radiations are accepted by carotenoids, flavins, cryptochromes in addition to phytochromes. The photomorphogenic process of phytochrome-mediated flavonoid biosynthesis has been observed in Amaranthus, barley, maize, Sorghum and turnip. Red light promotes flavonoid synthesis.
Availability through microorganisms
Research has shown production of flavonoid molecules from genetically engineered microorganisms.
Tests for detection
Shinoda test
Four pieces of magnesium filings are added to the ethanolic extract followed by few drops of concentrated hydrochloric acid. A pink or red colour indicates the presence of flavonoid. Colours varying from orange to red indicated flavones, 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 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 procedure.
Quantification
Lamaison and Carnet have designed a test for the determination of the total flavonoid content of a sample (AlCI<sub>3</sub> 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 lipase can be used to catalyze the regioselective acylation of flavonoids.
See also
- Phytochemical
- List of antioxidants in food
- List of phytochemicals in food
- Phytochemistry
- Secondary metabolites
- Homoisoflavonoids, related chemicals with a 16 carbons skeleton
References
Further reading
Databases
- USDA Database for the Flavonoid Content of Selected Foods, Release 3.1 (December 2013); data for 506 foods in the 5 subclasses of flavonoids provided in a separate PDF updated May 2014
- FlavoDB, Bioinformatics Centre, India, November 2019