Flavonoids (or bioflavonoids; from the Latin word flavus, meaning yellow, their color in nature) are a class of polyphenolic secondary 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 two phenyl rings (A and B) and a heterocyclic ring (C, the ring containing the embedded oxygen). [1] [2] This carbon structure can be abbreviated C6-C3-C6. According to the IUPAC nomenclature, [3] [4] they can be classified into:
The three flavonoid classes above are all ketone-containing compounds and as such, anthoxanthins (flavones and flavonols). [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 a phloroglucinol substitution pattern.
In the 1930s, Albert Szent-Györgyi and other scientists discovered that Vitamin C alone was not as effective at preventing scurvy 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). The substances in question (hesperidin, eriodictyol, hesperidin methyl chalcone and neohesperidin) 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 called chalconoids, 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 important plant pigments for flower coloration, producing yellow or red/blue pigmentation in petals designed to attract pollinator 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 in the infection stage of their symbiotic 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 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 a root 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 the aglycones of anthocyanins; they use the flavylium (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 (or Dihydroquercetin), Dihydrokaempferol |
Include flavan-3-ols (flavanols), flavan-4-ols and flavan-3,4-diols.
Skeleton | Name |
---|---|
Flavan-3-ol (flavanol) | |
Flavan-4-ol | |
Flavan-3,4-diol (leucoanthocyanidin) |
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". [1] [10] 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. [1]
Foods with a high flavonoid content include parsley, onions, blueberries and strawberries, black tea, bananas, and citrus fruits. [11] One study found high flavonoid content in buckwheat. [12]
Citrus flavonoids include hesperidin (a glycoside of the flavanone hesperetin), quercitrin, rutin (two glycosides of quercetin, and the flavone tangeritin. The flavonoids are less concentrated in the pulp than in the peels (for example, 165 versus 1156 mg/100 g in pulp versus peel of satsuma mandarin, and 164 vis-à-vis 804 mg/100 g in pulp versus peel of clementine). [13]
Peanut (red) skin contains significant polyphenol content, including flavonoids. [14] [15]
Food composition data for flavonoids were provided by the USDA database on flavonoids. [11] In the United States NHANES survey, mean flavonoid intake was 190 mg per day in adults, with flavan-3-ols as the main contributor. [17] In the European Union, based on data from EFSA, 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]
Neither the United States Food and Drug Administration (FDA) nor the European Food Safety Authority (EFSA) has approved any flavonoids as prescription drugs. [1] [18] [19] [20] The U.S. 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. [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 of uric acid resulting from flavonoid depolymerization and excretion. [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 as cancer, [26] cardiovascular disorders, [27] diabetes mellitus, [28] and celiac disease. [29] There is no clinical 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 small sample 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 improved endothelial function and reduced blood pressure (with a few studies showing inconsistent results). [1] Reviews of cohort 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 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. [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 concentrated hydrochloric acid. A pink or red colour indicates the presence of flavonoid. [39] Colours varying from orange to red indicated flavones, red to crimson indicated flavonoids, crimson to magenta indicated flavonones.
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. [40]
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. [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 of quercetin. [42] [43]
Immobilized Candida antarctica lipase can be used to catalyze the regioselective acylation of flavonoids. [44]
A nutrient is a substance used by an organism to survive, grow and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi and protists. Nutrients can be incorporated into cells for metabolic purposes or excreted by cells to create non-cellular structures such as hair, scales, feathers, or exoskeletons. Some nutrients can be metabolically converted into smaller molecules in the process of releasing energy such as for carbohydrates, lipids, proteins and fermentation products leading to end-products of water and carbon dioxide. All organisms require water. Essential nutrients for animals are the energy sources, some of the amino acids that are combined to create proteins, a subset of fatty acids, vitamins and certain minerals. Plants require more diverse minerals absorbed through roots, plus carbon dioxide and oxygen absorbed through leaves. Fungi live on dead or living organic matter and meet nutrient needs from their host.
Gallic acid (also known as 3,4,5-trihydroxybenzoic acid) is a trihydroxybenzoic acid with the formula C6H2(OH)3CO2H. It is classified as a phenolic acid. It is found in gallnuts, sumac, witch hazel, tea leaves, oak bark, and other plants. It is a white solid, although samples are typically brown owing to partial oxidation. Salts and esters of gallic acid are termed "gallates".
Flavan-3-ols are a subgroup of flavonoids. They are derivatives of flavans that possess a 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton. Flavan-3-ols are structurally diverse and include a range of compounds, such as catechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, proanthocyanidins, theaflavins, thearubigins. They play a part in plant defense and are present in the majority of plants.
Polyphenols are a large family of naturally occurring phenols. They are abundant in plants and structurally diverse. Polyphenols include phenolic acids, flavonoids, tannic acid, and ellagitannin, some of which have been used historically as dyes and for tanning garments.
Phytochemicals are chemical compounds produced by plants, generally to help them resist fungi, bacteria and plant virus infections, and also consumption by insects and other animals. The name comes from Greek φυτόν (phyton) 'plant'. Some phytochemicals have been used as poisons and others as traditional medicine.
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.
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 and is used as an ingredient in dietary supplements, beverages, and foods.
Rutin is the glycoside combining the flavonol quercetin and the disaccharide rutinose. It is a flavonoid glycoside found in a wide variety of plants, including citrus.
Kaempferol (3,4′,5,7-tetrahydroxyflavone) is a natural flavonol, a type of flavonoid, found in a variety of plants and plant-derived foods including kale, beans, tea, spinach, and broccoli. Kaempferol is a yellow crystalline solid with a melting point of 276–278 °C (529–532 °F). It is slightly soluble in water and highly soluble in hot ethanol, ethers, and DMSO. Kaempferol is named for 17th-century German naturalist Engelbert Kaempfer.
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 polyphenols, having the same polymeric building block, form the group of condensed tannins.
A polyphenol antioxidant is a hypothesized type of antioxidant studied in vitro. Numbering over 4,000 distinct chemical structures mostly from plants, such polyphenols have not been demonstrated to be antioxidants in vivo.
The flavanones, a type of flavonoids, are various aromatic, colorless ketones derived from flavone that often occur in plants as glycosides.
Flavonols are a class of flavonoids that have the 3-hydroxyflavone backbone. Their diversity stems from the different positions of the phenolic –OH groups. They are distinct from flavanols such as catechin, another class of flavonoids, and an unrelated group of metabolically important molecules, the flavins, derived from the yellow B vitamin riboflavin.
Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is the ester of epigallocatechin and gallic acid, and is a type of catechin.
Dry cocoa solids are the components of cocoa beans remaining after cocoa butter, the fatty component of the bean, is extracted from chocolate liquor, roasted cocoa beans that have been ground into a liquid state. Cocoa butter is 46% to 57% of the weight of cocoa beans and gives chocolate its characteristic melting properties. Cocoa powder is the powdered form of the dry solids with a small remaining amount of cocoa butter. Untreated cocoa powder is bitter and acidic. Dutch process cocoa has been treated with an alkali to neutralize the acid.
Flavonoids are synthesized by the phenylpropanoid metabolic pathway in which the amino acid phenylalanine is used to produce 4-coumaroyl-CoA. 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. 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.
Phenolic compounds—natural phenol and polyphenols—occur naturally in wine. These include a large group of several hundred chemical compounds that affect the taste, color and mouthfeel of wine. These compounds include phenolic acids, stilbenoids, flavonols, dihydroflavonols, anthocyanins, flavanol monomers (catechins) and flavanol polymers (proanthocyanidins). This large group of natural phenols can be broadly separated into two categories, flavonoids and non-flavonoids. Flavonoids include the anthocyanins and tannins which contribute to the color and mouthfeel of the wine. The non-flavonoids include the stilbenoids such as resveratrol and phenolic acids such as benzoic, caffeic and cinnamic acids.
The phenolic content in tea refers to the phenols and polyphenols, natural plant compounds which are found in tea. These chemical compounds affect the flavor and mouthfeel of tea. Polyphenols in tea include catechins, theaflavins, tannins, and flavonoids.