Tag Archives: flavanols or cathechins

Proanthocyanidins: definition, structure and absorption

Proanthocyanidins or condensed tannins, also called pycnogenols and leukocyanidins, are polyphenolic compounds (in particular they are a flavonoid subgroup) widely distributed in the plant kingdom, second only to lignin as the most abundant phenol in nature.
They are present in high concentrations in various parts of the plants such as flowers, fruits, berries, seeds (e.g. in grape seeds), and bark (e.g. pine bark).

Together with anthocyanins and their oxidation products, and catechins, they are the most abundant flavonoids in human diet and it has been suggested that they constitute a significant fraction of the polyphenols ingested in the Western diet.
Therefore, condensed tannins should be taken into consideration when the epidemiological association between the intake of polyphenols, especially flavonoids, and chronic diseases are examined.

CONTENTS

Chemical structure of proanthocyanidins

Condensed tannins have a complex chemical structure being oligomers (dimers to pentamers) or polymers (six or more units, up to 60) of catechins or flavanols, which are joined by carbon-carbon bonds.

Proanthocyanidins
Fig. 1 – Procyanidin Skeleton

They may consist exclusively of:

  • (epi)catechin, and they are named procyanidins;
  • (epi)afzelechin, and they are named propelargonidins;
  • (epi)gallocatechin, and they are named prodelphinidins.

Propelargonidins and prodelphinidins are less common in nature and in foods than procyanidins.

Depending on the bonds between monomers, proanthocyanidins have a:

  • B-type structure, if the polymerization occurs via carbon-carbon bond between the position 8 of the terminal unit and the 4 of the extender (or C4-C6);
  • A-type structure, less frequent, if monomers are doubly linked via an ether bond C2-O-C7 or C2-O-C5 plus a B-type bond.

Procyanidins

The most common dimers are B-type procyanidins, B1 to B8, formed by catechin or epicatechin; in B1, B2, B3 and B-4 dimers, the two flavanol units are joined by a C4-C8 bond; in B5, B6, B7 and B8 dimers the two units are joined by C4-C6 bond.

Proanthocyanidins
Fig. 2 – Procyanidins B1-B4

Procyanidin C1 is a B-type trimer.

Procyanidin A-2 is an example of A-type procyanidin.

Intestinal absorption of proanthocyanidins

Condensed tannins are poorly absorbed from the intestine; together with anthocyanins and gallic acid ester derivatives of tea catechins, they are the least well-absorbed polyphenols.
It seems that low molecular weight oligomers (2-3 monomers) may be absorbed as such while polymers are not.
In the systemic circulation, dimers reach concentrations of two orders of magnitude lower than those of catechins.
It seems that condensed tannins with a degree of polymerization greater than three transit into the stomach and small intestine without significant modifications, and then, into the large intestine, they are catabolized by colonic microflora, with production of phenylpropionic, phenilvaleric and phenylacetic acids. These degradation products have been suggested to be the major metabolites of proanthocyanidins in healthy humans.

Procyanidins and catechins

It had been proposed that the catabolism of procyanidins in the gastrointestinal tract lead to the release of monomeric catechins, thus indirectly contributing to their systemic pool in humans. In recent years, it has been shown that this does not happen because procyanidins do not significantly contribute to:

  • the concentration of catechin metabolites in the systemic circulation;
  • the total catechin metabolites excreted in the urine;
  • finally, they do not significantly affect plasma metabolite profile derived from catechol-O-methyltransferase activity.

Therefore, analyzing the potential health benefits associated with the intake of foods containing these phytochemicals, catechins and procyanidins should be considered distinct classes of related compounds.

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

Gu L., Kelm M.A., Hammerstone J.F., Beecher G., Holden J., Haytowitz D., Gebhardt S., and Prior R.L. Concentrations of proanthocyanidins in common foods and estimations of normal consumption. J Nutr 2004;134(3):613-617. doi:10.1093/jn/134.3.613

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 doi:10.1093/ajcn/79.5.727

Nandakumar V., Singh T., and Katiyar S.K. Multi-targeted prevention and therapy of cancer by proanthocyanidins. Cancer Lett 2008;269(2):378-387. doi:10.1016/j.canlet.2008.03.049

Ottaviani J.I., Kwik-Uribe C., Keen C.L., and Schroeter H. Intake of dietary procyanidins does not contribute to the pool of circulating flavanols in humans. Am J Clin Nutr 2012;95:851-8. doi:10.3945/ajcn.111.028340

Santos-Buelga C. and Scalbert A. Proanthocyanidins and tannin-like compounds: nature, occurrence, dietary intake and effects on nutrition and health. J Sci Food Agr 2000;80(7):1094-1117. doi:10.3390/nu2121231

Wang Y.,Chung S., Song W.O., and Chun O.K. Estimation of daily proanthocyanidin intake and major food sources in the U.S. diet. J Nutr 2011;141(3):447-452. doi:10.3945/jn.110.133900


Catechins: definition, structure, green tea, black tea, cocoa

Catechins or flavanols, with flavonols such as quercetin, and flavones such as luteolin, are a subgroup of flavonoids among the most widespread in nature.
Flavanols and proanthocyanidins, together with anthocyanins and their oxidation products, are the most abundant flavonoids in human diet.

CONTENTS

Chemical structure of catechins

Chemically they differ from many other flavonoids as:

  • they lack the double bond between positions 2 and 3 of the C ring;
  • they not have a keto group at position 4;
  • they have a hydroxyl group in position 3, and for this reason they are also called flavan-3-ols.
Catechins
Fig. 1 – Basic Flavanol Skeleton

Another distinctive feature of flavan-3-ols is their ability to form oligomers (two to ten units) or polymers (eleven or more units, up to 60 units) called proanthocyanidins or condensed tannins.

Catechins in foods

Flavanols commonly found in plant-derived food products are catechin, epicatechin, gallocatechin, epigallocatechin, and their gallic acid ester derivatives: catechin gallate, gallocatechin gallate, epicatechin gallate, and epigallocatechin gallate or EGCG.

Catechins
Fig. 2 – Flavanols

Flavanols present with higher frequency are catechin and epicatechin, which are also among the most common known flavonoids, and almost as popular as the related flavonol quercetin.
Cocoa and green tea are by far the richest sources in flavanols. In these foods the main flavonoids are catechin and epicatechin (cocoa is also a good source of epigallocatechin), but also their gallic acid ester derivatives, the gallocatechins.
However, they are also present in many fruits, especially in the skins of apples, blueberries (Vaccinium myrtillus) and grapes, in vegetables, red wine and beer, and peanuts.
As in many cases flavanols are present in the seeds or peels of fruits and vegetables, their intake may be limited by the fact that these parts are discarded during processing or while eaten.
Furthermore, in contrast to other flavonoids, catechins are not glycosylated in foods.
Proanthocyanidins, that is polymeric flavan-3-ols, are also commonly found in plant-derived food products. Their presence has been reported in the skin of peanuts and almonds, as in the berries.

Green and black tea

Green tea is an excellent source of flavonoids. The main flavonoids present in the leaves of the tea (as in cocoa beans) are catechin and epicatechin, monomeric flavanols, together with their gallate derivatives such as EGCG.
Epigallocatechin gallate is the most abundant catechin in green tea and it seems to have an important role in determining green tea benefits, as the reduction of:

  • vascular inflammation;
  • blood pressure;
  • concentration of oxidized LDL.

Black tea (fermented tea) contains fewer monomeric flavanols, as they are oxidized during fermentation of the leaves to more complex polyphenols such as theaflavins (theaflavin digallate, theaflavin-3-gallate, and theaflavin-3′-gallate, all dimers) and thearubigins (polymers).
Theaflavins and thearubigins are present only in the tea; their concentrations in brewed tea are between 50- and 100-folds lesser than in tea leaves.

It should be noted that tea epicatechins are remarkably stable to heat in acidic environment: at pH 5, only about 15% is degraded after seven hours in boiling water (therefore, adding lemon juice to brewed tea does not cause any reduction in their content).

Cocoa and cocoa products

Cocoa has the highest content of polyphenols and flavanols per serving, a concentration greater than those found in green tea and red wine. Most of the flavonoids present in cocoa beans and derived products, such as black chocolate, are catechin and epicatechin, monomeric flavanols, but also epigallocatechin, and their derivatives such as the gallocatechins; among polymers, proanthocyanidins are also important.

Fruits, vegetables, and legumes

Catechin and epicatechin are the main flavanols in fruits. They are found in many fruits in different concentrations, respectively, between 5-3 and 0.5-6 mg/100 g fresh weight.
On the contrary, gallocatechin, epicatechin gallate, epigallocatechin, and epigallocatechin gallate are present in various fruits such as red grapes, berries, apples, peaches and plums, but in very low concentrations, less than 1mg/100 g fresh weight.
Except for lentils and broad beans, few legumes and vegetables contain catechins, and in very low concentrations, less than 1.5 mg/100 g fresh weight.

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

de Pascual-Teresa S., Moreno D.A. and García-Viguera C. Flavanols and anthocyanins in cardiovascular health: a review of current evidence. Int J Mol Sci 2010;11:1679-1703. doi:10.3390/ijms11041679

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 doi:10.1093/ajcn/79.5.727

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


Flavonoids: definition, structure and classification

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.

CONTENTS

Chemical structure of flavonoids

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.

Flavonoids: the Skeleton
Fig. 1 – Skeleton of Diphenylpropane

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.

Classification

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.

Flavonoids: the Subgroups
Fig. 2 – Flavonoid Subgroups
  • 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.

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 doi:10.1093/ajcn/79.5.727

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