Tag Archives: flavonols

Polyphenols in grapes and wine: chemical composition and biological activities

Polyphenols in grapes and wine: contents in brief

Polyphenols in Grapes
Fig. 1 – Red Grapes

The consumption of grapes and grape-derived products, particularly red wine but only at meals, has been associated with numerous health benefits, which include, in addition to the antioxidant/antiradical effect, also anti-inflammatory, cardioprotective, anticancer, antimicrobial, and neuroprotective activities.
Grapes contain many nutrients such as sugars, vitamins, minerals, fiber and phytochemicals. Among the latter, polyphenols are the most important compounds in determining the health effects of the fruit and derived products.
Indeed, grapes are among the fruits with highest content in polyphenols, whose composition is strongly influenced by several factors such as:

  • cultivar;
  • climate;
  • exposure to disease;
  • processing

Nowadays, the main species of grapes cultivated worldwide are: European grapes, Vitis vinifera, North American grapes, Vitis rotundifolia and Vitis labrusca, and French hybrids.
Note: grapes are not a fruit but an infructescence, that is, an ensemble of fruits (berries): the bunch of grapes. In turn, it consists of a peduncle, a rachis, cap stems or pedicels, and berries.

⇑ Back to the top ⇑

What are polyphenols in grapes and wine?

Polyphenols in red grapes and wine are significantly higher, both in quantity and variety, than in white ones. This, according to many researchers, would be the basis of the more health benefits related to the consumption of red grapes and wine than white grapes and derived products.
Polyphenols in grapes and wine are a complex mixture of flavonoid compounds, the most abundant group, and non-flavonoid compounds.
Among flavonoids, they are found:

Among non-flavonoid polyphenols:

Most of the flavonoids present in wine derive from the epidermal layer of the berry skin, while 60-70% of the total polyphenols are present in the grape seeds. It should be noted that more than 70% of grape polyphenols are not extracted and remain in the pomace.
The complex chemical interactions that occur between these compounds, and between them and the other compounds of different nature present in grapes and wine, are probably essential in determining both the quality of the grapes and wine and the broad spectrum of therapeutic effects of these foods.
In wine, the mixture of polyphenols play important functions being able to influence:

  • bitterness;
  • astringency;
  • red color, of which they are among the main responsible;
  • sensitivity to oxidation, being molecules easily oxidizable by atmospheric oxygen.

Finally, they act as preservatives and are the basis of long aging.

⇑ Back to the top ⇑

Polyphenols in grapes and wine: anthocyanins

They are flavonoids widely distributed in fruits and vegetables.
They are primarily located in the berry skin (in the outer layers of the hypodermal tissue), to which they confer color, having a hue that varies from red to blue. In some varieties, called “teinturier”, they also accumulate in the flesh of the berry.
There is a close relationship between berry development and the biosynthesis of anthocyanins. The synthesis starts at veraison (when the berry stops growing and changes its color), causes a color change of the berry that turns purple, and reaches the maximum levels at complete ripening.
Among wine flavonoids, they are one of the most potent antioxidants.
Each grape species and cultivars has a unique composition of anthocyanins. Moreover, in grapes of Vitis vinifera, due to a mutation in the gene coding for 5-O-glucosyltransferase, mutation that determines the synthesis of an inactive enzyme, only 3-monoglucoside derivatives are synthesized, while in other species  the glycosylation at position 5 also occurs. Interestingly, 3-monoglucoside derivatives are more intensely colored than 3,5-diglucoside derivatives.

Polyphenols in Grapes
Fig. 2 – Malvidin-3-glucoside

In red grapes and wine, the most abundant anthocyanins are the 3-monoglucosides of malvidin (the most abundant one both in grapes and wine), petunidin, delphinidin, peonidin, and cyanidin. In turn, the hydroxyl group at position 6 of the glucose can be acylated with an acetyl, caffeic or coumaric group, acylation that further enhances the stability.
Anthocyanidins, namely the non-conjugated molecules, are not present in grapes and in wine, except as traces.
Anthocyanins are scarcely present in white grapes and wine.
The composition of anthocyanins in wine is highly influenced both by the type of cultivar and by processing techniques, since they are present in wine as a result of extraction by maceration/fermentation processes. For this reason, wines deriving from similar varieties of grapes can have very different anthocyanin compositions.
Together with proanthocyanidins, they are the most important polyphenols in contributing to some organoleptic properties of red wine, as they are primarily responsible for astringency, bitterness, chemical stability against oxidation, as well as of the color of the young wine. In this regard, it should be underscored that with time their concentration decreases, while the color is due more and more to the formation of polymeric pigments produced by condensation of anthocyanins both among themselves and with other molecules.
During wine aging, proanthocyanidins and anthocyanins react to produce more complex molecules that can  partially precipitate.

⇑ Back to the top ⇑

Polyphenols in grapes and wine: flavanols or catechins

Polyphenols in Grapes
Fig. 3 – Catechin

They are, together with condensed tannins, the most abundant flavonoids, representing up to 50% of the total polyphenols in white grapes and between 13% and 30% in red ones.
Their levels in wine depend on the type of cultivar.
Typically, the most abundant flavanol in wine is catechin, but epicatechin and epicatechin-3-gallate are also present.

⇑ Back to the top ⇑

Polyphenols of grapes and wine: proanthocyanidins or condensed tannins

Polyphenols in Grapes
Fig. 4 – Procyanidin C1

Composed of catechin monomers, they are present in the berry skin, seeds and rachis of the bunch of grapes as:

  • dimers: the most common are procyanidins B1-B4, but also procyanidins B5-B8 can be present;
  • trimers: procyanidin C1 is the most abundant;
  • tetramers;
  • polymers, containing up to 8 monomers.

Their levels in wine depend on the type of grape varieties and wine-making technology, and, like anthocyanins, are much more abundant in red wines, in particular in aged wines, compared to white ones.
In addition, as previously said, together with anthocyanins, condensed tannins are important in determining some organoleptic properties of the wine.

⇑ Back to the top ⇑

Polyphenols of grapes and wine: flavonols

They are present in a large variety of fruit and vegetables, even if in low concentrations.
They are the third most abundant group of flavonoids in grapes, after proanthocyanidins and catechins.
They are mainly present in the outer epidermis of the berry skin, where they play a role both in providing protection against UV-A and UV-B radiations and in copigmentation together with anthocyanins.
Flavanol synthesis begins in the sprout; the highest concentration is reached a few weeks after veraison, then it decreases as the berry increases in size.
Their total amount is very variable, with the red varieties often richer than the white ones.
In grapes, they are present as 3-glucosides and their composition depends on the type of grapes and cultivar:

  • the derivatives of quercetin, kaempferol and isorhamnetin are found in white grapes;
  • the derivatives of myricetin, laricitrin and syringetin are found, together with the previous ones, only in red grapes, due to the lack of expression in white grapes of the gene coding for flavonoid-3′,5′-hydroxylase.
Polyphenols in Grapes
Fig. 5 – Quercetin-3-glucoside

In general, the 3-glucosides and 3-glucuronides of quercetin are the major flavonols in most of the grape varieties. Conversely, quercetin-3-rhamnoside and quercetin aglycone are the major flavonols in muscadine grapes.
In wine and grape juice, unlike grapes, they are also found as aglycones, as a result of the acid hydrolysis that occurs during processing and storage. They are present in wine in a variable amount, and the major molecules are the glycosides of quercetin and myricetin, which alone represent 20-50% of the total flavonols in red wine.

⇑ Back to the top ⇑

Polyphenols in grapes and wine: hydroxycinnamates

Polyphenols in Grapes
Fig. 6 – Ferulic Acid

Hydroxycinnamic acids are the main class of non-flavonoid polyphenols in grapes and the major polyphenols in white wine.
The most important are p-coumaric, caffeic, sinapic, and ferulic acids, present in wine as esters with tartaric acid.
They have antioxidant activity and in some white varieties of Vitis vinifera, together with flavonols, are the polyphenols mainly responsible for absorbing UV radiation in the berry.

⇑ Back to the top ⇑

Polyphenols in grapes and wine: stilbenes

Polyphenols in Grapes
Fig. 7 – trans-Resveratrol

They are phytoalexins which are produced in low concentrations only by a few edible species, including grapevine (on the contrary, flavonoids are present in all higher plants).
Together with the other polyphenols in grapes and wine, also stilbenes, particularly resveratrol, have been associated with health benefits resulting from the consumption of wine.
Their content increases from the veraison to the ripening of the berry, and is influenced by the type of cultivar, climate, wine-making technology, and fungal pressure.
The main stilbenes present in grapes and wine are:

  • cis- and trans-resveratrol (3,5,4′-trihydroxystilbene);
  • piceid or resveratrol-3-glucopyranoside and astringin or 3′-hydroxy-trans-piceid;
  • piceatannol;
  • dimers and oligomers of resveratrol, called viniferins, of which the most important are:

α-viniferin, a trimer;
β-viniferin, a cyclic tetramer;
γ-viniferin, a highly polymerized oligomer;
ε-viniferin, a cyclic dimer.

In grapes, other glycosylated and isomeric forms of resveratrol and piceatannol, such as resveratroloside, hopeaphenol, or resveratrol di- and tri-glucoside derivatives, have been found in trace amounts.
Glycosylation of stilbenes is important for the modulation of antifungal activity, protection from oxidative degradation, and storage of the wine.
The synthesis of dimers and oligomers of resveratrol, both in grapes and wine, represents a defense mechanism against exogenous attacks or, on the contrary, the result of the action of extracellular enzymes released from pathogens in an attempt to eliminate undesirable compounds.

⇑ Back to the top ⇑

Polyphenols in grapes and wine: hydroxybenzoates

Polyphenols in Grapes
Fig. 8 – Gallic Acid

The hydroxybenzoic acid derivatives are a minor component in grapes and wine.
In grapes, gentisic, gallic, p-hydroxybenzoic and protocatechuic acids are the main ones.
Unlike hydroxycinnamates, which are present in wine as esters with tartaric acid, they are found in their free form.
Together with flavonols, proanthocyanidins, catechins, and hydroxycinnamates they are among the responsible of astringency of wine.

⇑ Back to the top ⇑

References

Andersen Ø.M., Markham K.R. Flavonoids: chemistry, biochemistry, and applications. CRC Press Taylor & Francis Group, 2006

Basli A, Soulet S., Chaher N., Mérillon J.M., Chibane M., Monti J.P.,1 and Richard T. Wine polyphenols: potential agents in neuroprotection. Oxid Med Cell Longev 2012. doi:10.1155/2012/805762

de la Rosa L.A., Alvarez-Parrilla E., Gonzàlez-Aguilar G.A. Fruit and vegetable phytochemicals: chemistry, nutritional value, and stability. 1th Edition. Wiley J. & Sons, Inc., Publication, 2010

Flamini R., Mattivi F.,  De Rosso M., Arapitsas P. and Bavaresco L. Advanced knowledge of three important classes of grape phenolics: anthocyanins, stilbenes and flavonols. Int J Mol Sci 2013;14:19651-19669. doi:10.3390/ijms141019651

Georgiev V., Ananga A. and Tsolova V. Recent advances and uses of grape flavonoids as nutraceuticals. Nutrients 2014;6: 391-415. doi:10.3390/nu6010391

Guilford J.M. and Pezzuto J.M. Wine and health: a review. Am J Enol Vitic 2011;62(4):471-486. doi:10.5344/ajev.2011.11013

He S., Sun C. and Pan Y. Red wine polyphenols for cancer prevention. Int J Mol Sci 2008;9:842-853. doi:10.3390/ijms9050842

Xia E-Q., Deng G-F., Guo Y-J. and Li H-B. Biological activities of polyphenols from grapes. Int J Mol Sci 2010;11-622-646. doi:10.3390/ijms11020622

Waterhouse A.L. Wine phenolics. Ann N Y Acad Sci 2002;957:21-36. doi:10.1111/j.1749-6632.2002.tb02903.x


Polyphenols in olive oil: variability and chemical composition

Polyphenols in olive oil: contents in brief

Polyphenols in olive oil: influences of environment and extraction process

Polyphenols in Olive Oil
Fig. 1 – Olives

Olive oil, which is obtained from the pressing of the olives, the fruits of olive tree (Olea europaea), is the main source of fat in the Mediterranean diet, and a good source of polyphenols.
Polyphenols, natural antioxidants, are present in olive pulp and, following pressing, they pass into the oil.
Note: olives are also known as drupes or stone fruits.
The concentration of polyphenols in olive oil is the result of a complex interaction between various factors, both environmental and linked to the extraction process of the oil itself, such as:

  • the place of cultivation;
  • the cultivars (variety);
  • the level of ripeness of the olives at the time of harvesting.
    Their level usually decreases with over-ripening of the olives, although there are exceptions to this rule. For example, in  warmer climates, olives produce oils richer in polyphenols, in spite of their faster maturation.
  • the climate;
  • the extraction process. In this regard, it is to underscore that the content of polyphenol in refined olive oil is not significant.

Any variation of the concentration of different polyphenols influence the taste, nutritional properties and stability of olive oil. For example, hydroxytyrosol and oleuropein (see below) give extra virgin olive oil a pungent and bitter taste.

⇑ Back to the top ⇑

Key polyphenols in olive oil

Among polyphenols in olive oil, there are  molecules with simple structure, such as phenolic acids and alcohols, and molecules with complex structure, such as flavonoids, secoiridoids, and lignans.

⇑ Back to the top ⇑

Flavonoids

Flavonoids include glycosides of flavonols (rutin, also known as quercetin-3-rutinoside), flavones (luteolin-7-glucoside), and anthocyanins (glycosides of delphinidin).

⇑ Back to the top ⇑

Phenolic acids and phenolic alcohols

Among phenolic acids, the first polyphenols with simple structure observed in olive oil, they are found:

  • hydroxybenzoic acids, such as, gallic, protocatechuic, and 4-hydroxybenzoic acids (all with C6-C1 structure).
  • hydroxycinnamic acids, such as  caffeic, vanillin, syringic, p-coumaric, and o-coumaric acids (all with C6-C3 structure).

Among phenolic alcohols, the most abundant are hydroxytyrosol (also known as  3,4-dihydroxyphenyl-ethanol), and tyrosol [also known as 2-(4-hydroxyphenyl)-ethanol].

⇑ Back to the top ⇑

Hydroxytyrosol

Polyphenols in olive oil
Fig. 2 – Hydroxytyrosol

Hydroxytyrosol can be present as:

  • simple phenol;
  • phenol esterified with elenolic acid, forming oleuropein and its aglycone;
  • part of the molecule verbascoside.

It can also be present in different glycosidic forms, depending on the –OH group to which the glucoside, i.e. elenolic acid plus glucose, is bound.
It is one of the main polyphenols in olive oil, extra virgin olive oil, and olive vegetable water.
In nature, its concentration, such as that of tyrosol, increases during fruit ripening, in parallel with the hydrolysis of compounds with higher molecular weight, while the total content of phenolic molecules and alpha-tocopherol decreases. Therefore, it can be considered as an indicator of the degree of ripeness of the olives.
In fresh extra virgin olive oil, hydroxytyrosol is mostly present in esterified form, while in time, due to hydrolysis reactions, the non-esterified form becomes the predominant one.
Finally, the concentration of hydroxytyrosol is correlated with the stability of olive oil.

⇑ Back to the top ⇑

Secoiridoids

They are the polyphenols in olive oil with the more complex structure, and are produced from the secondary metabolism of terpenes.
They are glycosylated compounds and are characterized by the presence of elenolic acid in their structure (both in its aglyconic or glucosidic form). Elenolic acid is the molecule common to glycosidic secoiridoids of Oleaceae.
Unlike tocopherols, flavonoids, phenolic acids, and phenolic alcohols, that are found in many fruits and vegetables belonging to different botanical families, secoiridoids are present only in plants of the Oleaceae family.
Oleuropein, demethyloleuropein, ligstroside, and nuzenide are the main secoiridoids.
In particular, oleuropein and demethyloleuropein (as verbascoside) are abundant in the pulp, but they are also found in other parts of the fruit. Nuzenide is only present in the seeds.

⇑ Back to the top ⇑

Oleuropein

Polyphenols in Olive Oil
Fig. 3 – Oleuropein

Oleuropein, the ester of hydroxytyrosol and elenolic acid, is the most important secoiridoid, and the main olive oil polyphenol.
It is present in very high quantities in olive leaves, as also in all the constituent parts of the olive, including peel, pulp and kernel.
Oleuropein accumulates in olives during the growth phase, up to 14% of the net weight; when the fruit turns greener, its quantity reduces. Finally, when the olives turns dark brown, color due to the presence of anthocyanins, the reduction in its concentration becomes more evident.
It was also shown that its content is greater in green cultivars than in black ones.
During the reduction of oleuropein levels (and of the levels of other secoiridoids), an increase of compounds such as flavonoids, verbascosides, and simple phenols can be observed.
The reduction of its content is also accompanied by an increase in its secondary glycosylated products, that reach the highest values in black olives.

⇑ Back to the top ⇑

Lignans

Polyphenols in olive oil
Fig. 4 – Lignans

Lignans, in particular (+)-1- acetoxypinoresinol and (+)-pinoresinol, are another group of polyphenols in olive oil.
(+)-pinoresinol is a common molecule in the lignin fraction of many plants, such as sesame (Sesamun indicum) and the seeds of the species Forsythia, belonging to the family Oleaceae. It has been also found in the olive kernel.
(+)-1- acetoxypinoresinol and (+)-1-hydroxypinoresinol, and their glycosides, have been found in the bark of the olive tree.
Lignans are not present in the pericarp of the olives, nor in leaves and sprigs that may accidentally be pressed with the olives.
Therefore, how  they can pass into the olive oil becoming one of the main phenolic fractions is not yet known.
(+)-1- acetoxypinoresinol and (+)-pinoresinol are absent in seed oils, are virtually absent from refined virgin olive oil, while they may reach a concentration of 100 mg/kg in extra-virgin olive oil.
As seen for simple phenols and secoiridoids, there is considerable variation in their concentration among olive oils of various origin, variability probably related to differences between olive varieties,  production areas, climate, and oil production techniques.

⇑ Back to the top ⇑

References

Cicerale S., Lucas L. and Keast R. Biological activities of phenolic compounds present in virgin olive oil. Int. J. Mol. Sci. 2010;11: 458-479. doi:10.3390/ijms11020458

de la Rosa L.A., Alvarez-Parrilla E., Gonzàlez-Aguilar G.A. Fruit and vegetable phytochemicals: chemistry, nutritional value, and stability. 1th Edition. Wiley J. & Sons, Inc., Publication, 2010

Manach C., Scalbert A., Morand C., Rémésy C., and Jime´nez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004;79(5):727-47 [Abstract]

Owen R.W., Mier W., Giacosa A., Hull W.E., Spiegelhalder B. and Bartsch H. Identification of lignans as major components in the phenolic fraction. Clin Chem 2000;46:976-988 [Abstract]

Tripoli E., Giammanco M., Tabacchi G., Di Majo D., Giammanco S. and La Guardia M. The phenolic compounds of olive oil: structure, biological activity and beneficial effects on human health. Nutr Res Rev 2005:18;98-112. doi:10.1079/NRR200495


Isoflavones: definition, structure and soy

Isoflavones: contents in brief

What are isoflavones?

Isoflavones are colorless polyphenols belonging to the class of flavonoids.
Unlike the majority of the other flavonoids, they have a restricted taxonomic distribution, being present almost exclusively in the Leguminosae or Fabaceae plant family, mainly in soy.
Since legumes, soy in primis, are a major part of the diet in many cultures, these flavonoids may have a great impact on human health.
They are also present in beans and broad beans, but in much lower concentrations than those found in soy and soy products.
Also red clover or meadow clover (Trifolium pratense), another member of Leguminosae family, is a good source.
Currently, they are not found in fruits and vegetables.

Together with phenolic acids, such as caffeic acid and gallic acid, and quercetin glycosides, they are the most well-absorbed polyphenols, followed by flavanones and catechins (but not gallocatechins).

In plants, some isoflavones have antimicrobial activity and are synthesized in response to attacks by bacteria or fungi; thus they act as phytoalexins.

⇑ Back to the top ⇑

Chemical structure of isoflavones

Isoflavones
Fig. 1 – Isoflavone Skeleton

While most flavonoids have B ring attached to position 2 of C ring, isoflavones have B ring attached to position 3 of C ring.
Even if they are not steroids, they have structural similarities to estrogens, particularly estradiol. This confers them pseudohormonal properties, such as the ability to bind estrogen receptors; therefore, they are classified as phytoestrogens or plant estrogens. The benefits often ascribed to soy and soy products (e.g. tofu) are believed to result from the ability of isoflavones to act as estrogen mimics .
It should be underlined that the binding to estrogen receptors seems to lose strength with time, therefore their potential efficacy should not be overestimated.
In foods, they are present in four forms:

  • aglycone;
  • 7-O-glucoside;
  • 6′-O-acetyl-7-O-glucoside;
  • 6′-O-malonyl-7-O-glucoside.

⇑ Back to the top ⇑

Soy isoflavones: genistein, daidzein and glycitein

Isoflavones
Fig. 2 – Isoflavones

Soy and soy products, such as soy milk, tofu, tempeh and miso, are the main source of isoflavones in the human diet.
The isoflavone content of soy and soy products varies greatly as a function of growing conditions, geographic zone, and processing; for example, in soy it ranges between 580 and 3800mg/kg fresh weight, while in soy milk it range between 30 and 175 mg/L. The most abundant isoflavones in soy and soy products are genistein, daidzein and glycitein, generally present in a concentration ratio of 1:1:0,2.; biochanin A and formononetin are other isoflavones present in less concentrations.
The 6′-O-malonyl derivatives have a bitter, unpleasant, and astringent taste; therefore they give a bad flavor to the food in which they are contained. However, being sensitive to temperature, they are often hydrolyzed to glycosides during processing, such as the production of soy milk.
The fermentation processes needed for the preparation of certain foods, such as tempeh and miso, determines in turn the hydrolysis of glycosides to aglycones, i.e. the sugar-free molecule.
Isoflavone glycosides present in soy and soy products can also be deglycosylated by β-glucosidases in the small intestine.
The aglycones are very resistant to heat.
Although many compounds present in the diet are converted by intestinal bacteria to less active molecules, other compounds are converted to molecules with increased biological activity. This is the case of isoflavones, but also of prenylflavonoids from hops (Humulus lupulus), and lignans, that are other phytoestrogens.

⇑ Back to the top ⇑

Soy isoflavones and menopause

Vasomotor symptoms, such as night sweats and hot flashes, and bone loss are very common in perimenopause, also called menopausal transition, and menopause. Hormone replacement therapy (HRT) has proved to be a highly effective treatment for the prevention of menopausal bone loss and vasomotor symptoms.
The use of alternative therapies based on phytoestrogens is increased as a result of the publication of the “Women’s Health Initiative” study, that suggests that hormone replacement therapy could lead to more risks than benefits, in particular an increased risk of developing some chronic diseases.
Soy isoflavones are among the most used phytoestrogens by menopausal women, often taken in the form of isoflavone fortified foods or isoflavone supplements.
However, many studies have highlighted the lack of efficacy of soy isoflavones, and red clover isoflavones, even in large doses, in the prevention of vasomotor symptoms (hot flushes and night sweats) and bone loss during menopause.

⇑ Back to the top ⇑

References

de la Rosa L.A., Alvarez-Parrilla E., Gonzàlez-Aguilar G.A. Fruit and vegetable phytochemicals: chemistry, nutritional value, and stability. 1th Edition. Wiley J. & Sons, Inc., Publication, 2010

Han X., Shen T. and Lou H. Dietary polyphenols and their biological significance. Int J Mol Sci 2007;9:950-988. doi:10.3390/i8090950

Lethaby A., Marjoribanks J., Kronenberg F., Roberts H., Eden J., Brown J. Phytoestrogens for menopausal vasomotor symptom. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No.: CD001395. doi:10.1002/14651858.CD001395.pub4

Manach C., Scalbert A., Morand C., Rémésy C., and Jime´nez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004;79(5):727-47 [Abstract]

Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrients 2010;2:1231-46. doi:10.3390/nu2121231


Flavonoids: definition, structure and classification

Flavonoids: contents in brief

What are flavonoids?

Flavonoids are the most abundant polyphenols in human diet, representing about 2/3 of all those ones ingested. Like other phytochemicals, they are the products of secondary metabolism of plants and, currently, it is not possible to determine precisely their number, even if over 4000 have been identified.
In fruits and vegetables, they are usually found in the form of glycosides and sometimes as acylglycosides, while acylated, methylated and sulfate molecules are less frequent and in lower concentrations.
They are water-soluble and accumulate in cell vacuoles.

⇑ Back to the top ⇑

Chemical structure of flavonoids

Flavonoids: the Skeleton
Fig. 1 – Skeleton of Diphenylpropane

Their basic structure is a skeleton of diphenylpropane, namely, two benzene rings (ring A and B, see figure) linked by a three carbon chain that forms a closed pyran ring (heterocyclic ring containing oxygen, the C ring) with benzenic A ring. Therefore, their structure is also referred to as C6-C3-C6.
In most cases, B ring is attached to position 2 of C ring, but it can also bind in position 3 or 4; this, together with the structural features of the ring B and the patterns of glycosylation and hydroxylation of the three rings, makes the flavonoids one of the larger and more diversified groups of phytochemicals, so not only of polyphenols, in nature.
Their biological activities, for example they are potent antioxidants, depend both on the structural characteristics and the pattern of glycosylation.

⇑ Back to the top ⇑

Classification of flavonoids

Flavonoids: the Subgroups
Fig. 2 – Flavonoid Subgroups

They can be subdivided into different subgroups depending on the carbon of the C ring on which B ring is attached, and the degree of unsaturation and oxidation of the C ring.
Flavonoids in which B ring is linked in position 3 of the ring C are called isoflavones; those in which B ring is linked in position 4, neoflavonoids, while those in which the B ring is linked in position 2 can be further subdivided into several subgroups on the basis of the structural features of the C ring. These subgroup are: flavones, flavonols, flavanones, flavanonols, flavanols or catechins and anthocyanins.
Finally, flavonoids with open C ring are called chalcones.

  • Flavones
    They have a double bond between positions 2 and 3 and a ketone in position 4 of the C ring. Most flavones of vegetables and fruits has a hydroxyl group in position 5 of the A ring, while the hydroxylation in other positions, for the most part in position 7 of the A ring or 3′ and 4′ of the B ring may vary according to the taxonomic classification of the particular vegetable or fruit.
    Glycosylation occurs primarily on position 5 and 7, methylation and acylation on the hydroxyl groups of the B ring.
    Some flavones, such as nobiletin and tangeretin, are polymethoxylated.
  • Flavonols
    Compared to flavones, they have a hydroxyl group in position 3 of the C ring, which may also be glycosylated. Again, like flavones, flavonols are very diverse in methylation and hydroxylation patterns as well, and, considering the different glycosylation patterns, they are perhaps the most common and largest subgroup of flavonoids in fruits and vegetables. For example, quercetin is present in many plant foods.
  • Flavanones
    Flavanones, also called dihydroflavones, have the C ring saturated; therefore, unlike flavones, the double bond between positions 2 and 3 is saturated and this is the only structural difference between the two subgroups of flavonoids.
    The flavanones can be multi-hydroxylated, and several hydroxyl groups can be glycosylated and/or methylated.
    Some have unique patterns of substitution, for example, furanoflavanones, prenylated flavanones, pyranoflavanones or benzylated flavanones, giving a great number of substituted derivatives.
    Over the past 15 years, the number of flavanones discovered is significantly increased.
  • Flavanonols
    Flavanonols, also called dihydroflavonols, are the 3-hydroxy derivatives of flavanones; they are an highly diversified and multisubstituted subgroup.
  • Isoflavones
    As anticipated, isoflavones are a subgroup of flavonoids in which the B ring is attached to position 3 of the C ring. They have structural similarities to estrogens, such as estradiol, and for this reason they are also called phytoestrogens.Neoflavonoids
    They have the B ring attached to position 4 of the C ring.
  • Flavanols or flavan-3-ols or catechins
    Flavanols are also referred to flavan-3-ols as the hydroxyl group is almost always bound to position 3 of C ring; they are called catechins as well.
    flavanols to have two chiral centers in the molecule, on positions 2 and 3, then four possible diastereoisomers. Epicatechin is the isomer with the cis configuration and catechin is the one with the trans configuration. Each of these configurations has two stereoisomers, namely, (+)-epicatechin and (-)-epicatechin, (+)-catechin and (-)-catechin.
    (+)-Catechin and (-)-epicatechin are the two isomers most often present in edible plants.
    Another important feature of flavanols, particularly of catechin and epicatechin, is the ability to form polymers, called proanthocyanidins or condensed tannins. The name “proanthocyanidins” is due to the fact that an acid-catalyzed cleavage produces anthocyanidins.
    Proanthocyanidins typically contain 2 to 60 monomers of flavanols.
    Monomeric and oligomeric flavanols (containing 2 to 7 monomers) are strong antioxidants.
  • Anthocyanidins
    Chemically, anthocyanidins are flavylium cations and are generally present as chloride salts.
    They are the only group of flavonoids that gives plants colors (all other flavonoids are colorless).
    Anthocyanins are glycosides of anthocyanidins. Sugar units are bound mostly to position 3 of the C ring and they are often conjugated with phenolic acids, such as ferulic acid.
    The color of the anthocyanins depends on the pH and also by methylation or acylation at the hydroxyl groups on the A and B rings.
  • Chalcones
    Chalcones and dihydrochalcones are flavonoids with open structure; they are classified as flavonoids because they have similar synthetic pathways.

⇑ Back to the top ⇑

References

de la Rosa L.A., Alvarez-Parrilla E., Gonzàlez-Aguilar G.A. Fruit and vegetable phytochemicals: chemistry, nutritional value, and stability. 1th Edition. Wiley J. & Sons, Inc., Publication, 2010

Han X., Shen T. and Lou H. Dietary polyphenols and their biological significance. Int J Mol Sci 2007;9:950-988. doi:10.3390/i8090950

Manach C., Scalbert A., Morand C., Rémésy C., and Jime´nez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004;79(5):727-47 [Abstract]

Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrients 2010;2:1231-1246. doi:10.3390/nu2121231