Flavonoids (orbioflavonoids; from the Latin wordflavus, meaning yellow, their color in nature) are a class ofpolyphenols or polyphenolicsecondary metabolites found in plants, and thus commonly consumed in the diets of humans.[1]
Chemically, flavonoids have the general structure of a 15-carbon skeleton, which consists of twophenyl rings (A and B) and aheterocyclic ring (C, the ring containing the embeddedoxygen).[1][2] This carbon structure can be abbreviated C6-C3-C6. According to theIUPAC nomenclature,[3][4]they can be classified into:
The three flavonoid classes above are allketone-containing compounds and as such,anthoxanthins (flavones andflavonols).[1] 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.[2] Ring A usually shows aphloroglucinol substitution pattern.
In the 1930s,Albert Szent-Györgyi and other scientists discovered thatVitamin C alone was not as effective at preventingscurvy 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 ofcapillaries). The substances in question (hesperidin,eriodictyol, hesperidin methyl chalcone andneohesperidin) were however later shown not to fulfil the criteria of a vitamin,[5] so that this term is now obsolete.[6]
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.[1] 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, flavonols, flavanones, flavan-3-ols, flavanonols, flavones, and isoflavones.[1] Chalcones, also calledchalconoids, although lacking the heterocyclic ring, are also classified as flavonoids. 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.[1]
Flavonoids are widely distributed in plants, fulfilling many functions.[1] They are the most importantplant pigments for flower coloration, producing yellow or red/blue pigmentation in petals designed to attractpollinator 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 helpRhizobia in the infection stage of theirsymbiotic relationship with legumes like peas, beans, clover, and soy. Rhizobia living in soil are able to sense the flavonoids and this triggers the secretion ofNod factors, 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 aroot nodule. In addition, some flavonoids have inhibitory activity against organisms that cause plant diseases, e.g.Fusarium oxysporum.[7]
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[8]):
Anthocyanidins are theaglycones ofanthocyanins; they use theflavylium (2-phenylchromenylium) ion skeleton.[1]
Anthoxanthins are divided into two groups:[9]
| 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,Galangin,Isorhamnetin,Pachypodol,Rhamnazin,Pyranoflavonols,Furanoflavonols, |
| Group | Skeleton | Examples | |||
|---|---|---|---|---|---|
| Description | Functional groups | Structural formula | |||
| 3-hydroxyl | 2,3-dihydro | ||||
| Flavanone | 2,3-dihydro-2-phenylchromen-4-one | ✗ | ✓ |  | Hesperetin,Naringenin,Eriodictyol,Homoeriodictyol |
| Group | Skeleton | Examples | |||
|---|---|---|---|---|---|
| Description | Functional groups | Structural formula | |||
| 3-hydroxyl | 2,3-dihydro | ||||
| Flavanonol or 3-Hydroxyflavanone or 2,3-dihydroflavonol | 3-hydroxy-2,3-dihydro-2-phenylchromen-4-one | ✓ | ✓ |  | Taxifolin (orDihydroquercetin),Dihydrokaempferol |
Includeflavan-3-ols (flavanols),flavan-4-ols andflavan-3,4-diols.
| Skeleton | Name |
|---|---|
 | Flavan-3-ol (flavanol) |
 | Flavan-4-ol |
 | Flavan-3,4-diol (leucoanthocyanidin) |
Flavonoids (specifically flavanoids such as thecatechins) are "the most common group ofpolyphenolic compounds in the human diet and are found ubiquitously in plants".[1][10] Flavonols, the original bioflavonoids such asquercetin, are also found ubiquitously, but in lesser quantities. The widespread distribution of flavonoids, their variety and their relatively lowtoxicity compared to other active plantcompounds (for instancealkaloids) mean that many animals, includinghumans, ingest significant quantities in their diet.[1]
Foods with a high flavonoid content includeparsley,onions,blueberries andstrawberries,black tea,bananas, andcitrus fruits.[11] One study found high flavonoid content inbuckwheat.[12]
Citrus flavonoids includehesperidin (a glycoside of the flavanonehesperetin),quercitrin,rutin (twoglycosides of quercetin, and the flavonetangeritin. The flavonoids are less concentrated in thepulp than in thepeels (for example, 165 versus 1156 mg/100 g in pulp versus peel ofsatsuma mandarin, and 164 vis-à-vis 804 mg/100 g in pulp versus peel ofclementine).[13]
Peanut (red) skin contains significant polyphenol content, including flavonoids.[14][15]
| Food source | Flavones | Flavonols | Flavanones |
|---|---|---|---|
| Red onion | 0 | 4–100 | 0 |
| Parsley, fresh | 24–634 | 8–10 | 0 |
| Thyme, fresh | 56 | 0 | 0 |
| Lemon juice, fresh | 0 | 0–2 | 2–175 |
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Food composition data for flavonoids were provided by theUSDA database on flavonoids.[11] In the United StatesNHANES survey, mean flavonoid intake was 190 mg per day in adults, withflavan-3-ols as the main contributor.[17] In theEuropean Union, based on data fromEFSA, mean flavonoid intake was 140 mg/d, although there were considerable differences among individual countries.[16] 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.[1][16][17]
_in_the_European_Union.png)
Neither the United StatesFood and Drug Administration (FDA) nor theEuropean Food Safety Authority (EFSA) has approved any flavonoids asprescription drugs.[1][18][19][20] The U.S. FDA has warned numerous dietary supplement and food manufacturers, includingUnilever, producer ofLipton tea in the U.S., about illegal advertising and misleadinghealth claims regarding flavonoids, such as that they lower cholesterol or relieve pain.[21][22]
Flavonoids are poorly absorbed in the human body (less than 5%), then are quickly metabolized into smaller fragments with unknown properties, and rapidly excreted.[1][20][23][24] 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 ofuric acid resulting from flavonoiddepolymerization andexcretion.[1] Microbial metabolism is a major contributor to the overall metabolism of dietary flavonoids.[1][25]
Inflammation has been implicated as a possible origin of numerous local and systemic diseases, such ascancer,[26]cardiovascular disorders,[27]diabetes mellitus,[28] andceliac disease.[29] There is noclinical evidence that dietary flavonoids affect any of these diseases.[1]
Clinical studies 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 smallsample size.[1][30] There is little evidence to indicate that dietary flavonoids affect human cancer risk in general.[1]
Although no significant association has been found between flavan-3-ol intake and cardiovascular disease mortality, clinical trials have shown improvedendothelial function and reducedblood pressure (with a few studies showing inconsistent results).[1] Reviews ofcohort studies 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.[1][31]
In 2013, the EFSA decided to permit health claims that 200 mg/day of cocoa flavanols "help[s] maintain the elasticity of blood vessels."[32][33] 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.[34][35]
Flavonoid synthesis in plants is induced by light color spectrums at both high and low energy radiations. Low energy radiations are accepted byphytochrome, while high energy radiations are accepted bycarotenoids,flavins,cryptochromes in addition to phytochromes. Thephotomorphogenic process of phytochrome-mediated flavonoid biosynthesis has been observed inAmaranthus,barley,maize,Sorghum andturnip. Red light promotes flavonoid synthesis.[36]
Research has shown production of flavonoid molecules from genetically engineered microorganisms.[37][38]
Four pieces of magnesium filings are added to the ethanolic extract followed by few drops of concentratedhydrochloric acid. A pink or red colour indicates the presence of flavonoid.[39] Colours varying from orange to red indicatedflavones, red to crimson indicated flavonoids, crimson to magenta indicatedflavonones.
About 5 mg of the compound is dissolved in water, warmed, and filtered. 10% aqueoussodium 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.[40]
A colorimetric assay based upon the reaction of A-rings with the chromogenp-dimethylaminocinnamaldehyde (DMACA) has been developed for flavanoids in beer that can be compared with thevanillin procedure.[41]
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 ofquercetin.[42][43]
ImmobilizedCandida antarctica lipase can be used to catalyze theregioselectiveacylation of flavonoids.[44]
