Plant polyphenols

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
 Classification
 References
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.

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.

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.
 

Actions of flavonoids 1-Flavonoids as antioxidants: The flavones and catechins seem to be the
most powerful flavonoids for protecting the body against reactive oxygen species (ROS).
Flavonoids are oxidized by radicals, resulting in a more stable, less-reactive radical. Because of
the high reactivity of the hydroxyl group of the flavonoids, radicals are made inactive.
Epicatechin and rutin are also powerful radical scavengers. 2- Anti ulcer effect: Majority of
peptic ulcers are associated with helicobacter pylori, a spiral-shaped bacterium that lives in the
acidic environment of the stomach. Quercetin seems to play a very important role in the
prevention and treatment of peptic ulcer. It acts by promoting mucus secretion, thereby serves as
gastroprotective agent, also quercetin has been shown to inhibit the growth of helicobacter pylori
bacterium in-vitro studies.
20. 3- Anti atherosclerotic effects: Atherosclerosis is a condition that results from the gradual
build-up of fatty substances, including cholesterol, on the walls of the arteries. This build-up,
called plaque, reduces the blood flow to the heart, brain and other tissues and can progress to
cause a heart attack or stroke. This process is commonly referred to as hardening of the arteries.
An elevated plasma low density lipoprotein (LDL) concentration is a primary risk factor for the
development of atherosclerosis and coronary artery disease. Flavonoids seems to suppress LDL
oxidation and inflammatory progression in the artery wall. A Japanese study reported an inverse
correlation between flavonoid intake and total plasma cholesterol concentrations, other clinical
studies, as mentioned earlier, stated that flavonoid intakes protect against coronary heart disease.
21. 4- Anti-inflammatory effect: Cyclooxygenase (COX) is an enzyme that plays an important
role as inflammatory mediator and is involved in the release of arachidonic acid, which is a
precursor for biosynthesis of eicosanoids like prostaglandins and prostacyclin. The release of
arachidonic acid can be considered starting point for a general inflammatory response. Select
flavonoids like quercetin are shown to inhibit the cyclooxygenase pathway. This inhibition
reduces the release of arachidonic acid.
22. 5-Hepatoprotective activity: Many flavonoids have also been found to possess hepato-
protective activity e.g silymarin, apigenin, quercetin and naringenin. The results of several
clinical

investigations showed the efficacy and safety of flavonoids in the treatment of hepato-biliary
dysfunction and digestive complaints, such as sensation of fullness, loss of appetite, nausea and
abdominal pain.

Tannins:

Tannins are naturally occurring complex organic compounds possessing nitrogen free

polyphenols of high molecular weight. They form colloidal solution with water giving acid

reactions. They also precipitate proteins and alkaloids. The astringent in nature of tannins is due

to the fact that they can precipitate proteins and render them resistant to enzymatic attack. When
applied on a wound or injury, tannins form a protective coating so as to prevent external

irritation and thus promote healing.

Classification of Tannins:

(i) Hydrolysable tannins

(ii) Condensed tannins

(iii) Pseudo tannins.

Hydrolysable tannins:

These tannins are hydrolyzed by acids, or enzyme and produce gallic acid and ellagic acid.

Chemically, these are esters of phenolic acid like gallic acid and ellagic acid. The tannins derived

from gallic acid are known as gallitannins and from that of ellagic acid are known as

gallitannins. The gallic acid is found in rhubarb, clove and ellagic acid is found in

eucalyptus leave and myrobalans and pomegranate bark. These tannins treated with ferric

chloride to produced blue or black colour.

Condensed tannins:

These tannins are resistant to hydrolysis and they derived from the flavonols, catechins and

flavan-3, 4-diols. On treatment with acids or enzymes they are decomposed into phlobaphenes.

On dry distillation condensed tannin produce catechol. These tannins are called as catechol

tannins. These tannins are found in cinchona bark, male fern, areca seeds, tea leaves and

wild cherry bark, bahera fruits, Amla, etc.

Pseudo tannins:

They are phenolic compounds of lower molecular weight and do not show the goldbeater’s test.

They are found in catechu and nux-vomica, etc.

Tanning is the process of treating skins and hides of animals to produce leather.