Mini-Reviews in Medicinal Chemistry, 2011, 11, 000-000
1389-5575/11 $58.00+.00 © 2011 Bentham Science Publishers
An Overview of Innovations in Analysis and Beneficial Health Effects of
Department of Chemistry, Faculty of Agriculture, J. J. Strossmayer University of Osijek, Osijek, Croatia
Abstract: Polyphenols are natural compounds that show a wide spectrum of biological actions potentially beneficial for
the human health. Wine is an alcoholic beverage that contains a large amount of polyphenols extracted from grapes during
the processes of vinification. These molecules are associated with anticancerogenic, antidiabetic, neuroprotective,
hormonal, antimicrobial, cardioprotective, and other health effects of wine. The present review provided an overview of
well know and recent achievement in analytical methodology for the analysis of polyphenols in wine, and their biological
Keywords: Wine, polyphenols, analysis, health effects, antioxidant activity, QSAR.
usually mixed with water, wine was most hygienic drink.
Today, moderate consumption of wine complements food,
stimulates the senses, and promotes society between people
Over the centuries, wine has been basic foodstuff, and
recognized by epidemiological studies that implied on
positive relation between lower rates of coronary heart
diseases (CHD) mortality and regular, but moderate
consumption of wine. The “French Paradox” is a term that
described appearance of lower incidence of the heart disease
in France, despite of higher fat diet, compared with many
other Western European countries and the United States .
Such beneficial effects of red wine have been related to both,
the alcohol and antioxidant activities of red wine
polyphenols . However, the multi-national cardiovascular
disease research (MONICA) coordinated by WHO produced
relevant evidence that French coronary death rates are
comparable to those among their contiguous countries at the
same latitude, and denies there is a “French Paradox” .
About thirty years ago, health benefits of wine have been
beneficial health effects, such as antibacterial , antiviral
, anti-carcinogenic , and anti-atherogenic activities .
Although wine may help protect against various diseases,
alcohol may have adverse effect on health. Immoderate wine
consumption has been associated with increased risk of:
hypertension, oral and oesophageal cancer, cirrhosis breast
cancer, gall stones, and kidney stones .
Moreover, wine polyphenols manifest a wide range of
polyphenols are also responsible for wine quality by
contributing to the colour, astringency, and bitterness .
Besides of pharmacological and biological properties,
*Address correspondence to this author at the Department of Chemistry,
Faculty of Agriculture, J. J. Strossmayer University of Osijek, Trg Sv.
Trojstva 3, P.O. Box 719, Osijek, 31 107, Croatia; Tel: +385 31 224225;
Fax: +385 31 207017; E-mail: firstname.lastname@example.org
have been performed to analyze polyphenols in wine by
means of various methods,
chromatography (TLC) , high-performance liquid
chromatography (HPLC) , capillary electrophoresis (CE)
, and nuclear magnetic resonance (NMR) spectroscopy
Therefore, during the last decades, numerous studies
discussed a recent achievement in analytical methodology
for the analysis of polyphenols in wine, and their biological
activity with some aspects of bioavailability.
The aim of the present review is to compile and
POLYPHENOLS IN WINE
of grapes is extracted into wines during the processes of
vinification . The structures of main polyphenols present
in wine are given in Fig. (1).
Polyphenols contained within the skin, seeds, and flesh
possess one common structural feature – an aromatic ring
bearing at least one hydroxyl group. Phenolic acids are
divided into two sub-groups: hydroxycinnamic acids
(caffeic, ferulic, p-coumaric acid) and hydroxybenzoic acids
(gallic, syringic, vanillic acid), and their esters. During the
fermentation and ageing of wine, hydroxycinnamic acids and
hydroxybenzoic acids change their forms and content.
The simplest polyphenols are phenolic acids, which
browning. Differences in hydroxybenzoic acids and
hydroxycinnamic acids content influence on the colour of
white wine. These compounds are involved in formation of
yellow or brown pigments that affect on quality of white
Some of the phenolic acids are involved in wine
derived from flavan (2-phenol-benzo-dihydropyran) and are
divided into few sub-groups: anthocyanidins, flavones and
flavonoles, flavanones and flavanols. Their chemical
variation is present in the basic structure (hydroxylation,
methoxylation), the degree of polymerization, and the type
of conjugation, such as glycosylation. Flavonoids are present
More complex compounds are flavonoids. Flavonoids are
2 Mini-Reviews in Medicinal Chemistry, 2011, Vol. 11, No. 13 V. Rastija
in the grape mainly in the monoglycoside form, with the
sugar residue linked to the hydroxyl group in position C-3 of
the C ring. Flavanols (catechins) are present in the grape as
monomers or polymerized to form proanthocyanidins,
procyanidins, and hydrolysable tannins . Anthocyanins,
in their flavilium cation form, are responsible for the colour
of red berry varieties and red wines. In the red wine grapes,
they are present as mono- or diglucosides, depending on
variety, with the second glucose molecule linked to the C-5
hydroxyl group. In the grapes, they are exist as monomers,
which during the winemaking process participate in
formation of copigmentation complexes, oxidation and in
chemical reactions as, oxidation, and linking to another
polyphenols and secondary yeast metabolites . The
structures of some wine pigments are showed in Fig. (2).
Factors Influencing Polyphenolic Content in Wine
by intrinsic factor such as grape variety, and extrinsic factor
such as atmospheric conditions, processes of viticulture and
techniques employed during vinification.
Content and profile of polyphenols in wine is influenced
grapes may vary largely in the polyphenolic composition.
Therefore, the examination of polyphenolic composition
using different techniques, such as HPLC [19, 20], CE ,
and NMR  is an indispensable element in choosing the
Because of their unique varietal (genetic) diversity,
appropriate grape varieties and selecting the technological
applications that enable the production of high quality wines.
By means of multivariate data analysis, such as principle
components analysis, cluster analysis, and artificial neural
networking, it is possible to obtain the classification of the
grape varietals based on their different polyphenolic content
response to increase light exposure, especially ultraviolet-B
rays. Consequently, grapes exposed to increased daylight are
capable of increased flavonoid biosynthesis, so high total
flavonols levels in red wines have been associated with the
grapes grown in a sunnier microclimate. Increased grape
exposure to sunlight improves a content of total phenols and
total anthocyanins in grape and wine .
Thus, wines made from highly and moderately exposed
cluster positions at higher altitude, have a higher total
anthocyanins levels than those from shaded clusters [23, 24].
Therefore, flavonols content in wines from Croatia is
associated with the geographical origins, since higher level
of polyphenols were detected in wines from the Coastal
region, which has a Mediterranean climate, as opposed of
other parts of Croatia with continental climate .
The accumulation of flavonoids in grapes is enhanced in
modified by environmental conditions and viticultural
Moreover, the polyphenolic content in the grape can be
vanillic acid (3-OCH3, 4-OH)
syringic acid (3,5-OCH3, 4-OH)
gallic acid (3,4,5-OH)
o-hydroxycinnamic acid (2-OH, R = H)
p-hydroxycinnamic acid (4-OH, R = H)
ferulic acid (3-OCH3, 4-OH, R = H)
caffeic acid (3,4-OH, R = H)
chlorogenic acid (3,4-OH, R = quinic acid)
malvidin (3,5,7,4',-OH, 3',5'-OCH3,
Fig. (1). Structures of main polyphenols present in wine.
Innovations of Analysis and Health Effects of Wine Polyphenols
Mini-Reviews in Medicinal Chemistry, 2011, Vol. 11, No. 13 3
practices. Moderate nitrogen and potassium fertilisation
before bloom favour increases synthesis of polyphenols in
the grape. Indeed, excessive or unbalanced fertilisation may
have negative effects on polyphenolic content. Wines made
from high-quality grapes, with higher ratio of skin to
volume, have higher concentrations of skin-derived
polyphenols, e.g. anthocyanins . Also, an excessively
large harvest will result in decreased concentrations of
polyphenols within harvested grapes .
destemming of grape clusters, and addition of a
supplementary quantity of seeds to musts, fermentation
conditions, etc.) greatly influence in polyphenolic content.
The experiments have showed that there is a progressive
increase in the content of catechins and proanthocyanidins,
but decrease in total and some individual anthocyanins, with
the increased length of maceration time. Similarly, the
presence of stems during fermentation gives wines with a
higher content of catechins and proanthocyanidins.
Significant differences have found in composition of various
phenolic compounds (catechins, oligomeric, and polymeric
proanthocyanidins, anthocyanins) and volatile compounds
(alcohols and esters) between red wines made by different
winemaking technologies. The carbonic maceration wine had
less colour intensity, lower concentrations of polyphenols,
but higher concentrations of volatile compounds than the
skin fermentation wines [27, 28]. Post-fermentation
Winemaking techniques (time of maceration,
treatments, such as fining, were found to cause significant
reduction in both flavonol glycosides and aglycones in
are also associated with ageing and storage conditions.
Aging in oak wood allows wine to extract a series of benzoic
and cinnamic compounds (vanillin, vanillinic acid, syrin-
galdehyde, syringic acid, coniferaldehyde, sinapaldehyde),
gallic acid, ellagic acid and cummarines (scopoletine,
umbelliferone). Therefore, wines produced by fermentation
and maturation in oak barrels have different flavour
characteristics to those, which have undergone barrel
maturation only after fermentation in stainless steel .
Yeast metabolites, such as pyruvic acid and acetaldehyde
react with different classes of polyphenols and thereby affect
on stabilization of pigments during the maturation and
ageing of wine. Therefore,
Saccharomyces cerevisiae, employed for winemaking, may
influence on colour, content of polyphenols and antioxidant
power of wine .
Factors that may affect on the polyphenolic composition
choice of strain of
ANALYSIS OF POLYPHENOLS FROM WINE
detection methods have been developed to isolate and
determine polyphenols in wine. Sample handling strategies
and analytical methods depend on: the nature of the analyte
(e.g., glycosides or individual compounds; monomeric or
Over the years many sample preparation, separation and
Fig. (2). Structures of some pigments identified in wine. (Glu = glucose).
4 Mini-Reviews in Medicinal Chemistry, 2011, Vol. 11, No. 13 V. Rastija
polymeric species); the specific class of polyphenols that
needs to be analyzed (e.g., only phenolic acid, only
anthocyanins, only flavanols); and, finally, the type of
equipment available in the laboratory. HPLC determination
of polyphenols in propolis and wine, including sample
preparation, chromatographic conditions, and detection of
polyphenols in wine has recently been reviewed .
Therefore, in this paper many sample preparation methods
will be failed and very recent HPLC methods will be
discussed briefly. Special attention will be devoted to the use
of thin-layer chromatography and capillary electrophoresis,
gas chromatography (GC), as well as various detection
methods and structural characterization.
method for relatively fast separation and identification of the
phenolic compounds present in wine sample. Qualitative
analysis of the fractions of wine proanthocyanidins obtained
by solid-phase extraction and separated on the basis of their
degree of polymerization . Information theory and
clustering methods have been used to select and evaluate the
efficiency of 11 used mobile phases for the determination of
polyphenols in wines from the Croatia. Application of most
appropriate mobile phase (benzene-ethyl acetate-formic acid,
30:15:5 (v/v)) was allowed identification of several
polyphenolic compounds . Densitometric quantitative
analysis of polyphenols in wine extracts is usually performed
by scanning the TLC plates with ultraviolet (UV) light at
wavelengths of 350–365 nm or 250–260 nm. TLC
quantification of polyphenols in wine was performed using
CAMAG system. The substances were identified on basis of
retention factor (RF) values and UV spectra . The colour
pigments from red wine could be efficiently separated using
a reversed-phase thin-layer chromatographic (RP-TLC)
method with acetonitrile-water-formic acid, 40:58:2 (v/v) as
mobile phase . Anthocyanins and polymeric pigments in
red wines have been also separated by high performance thin
layer chromatography (HPTLC) method using C18 silica gel
plates with isocratic elution
trifluoracetic acid, 55:45:1 (v/v) .
Thin-layer chromatography on silica gel sheets is good
for the analysis of polyphenols in wine. The most common
method used for the analysis of polyphenols in wine is
reverse phase HPLC (RP-HPLC) analysis using gradient
elution systems [12, 19, 25, 37]. Polymeric-based reversed-
phase column has been used for analysis of monomeric and
polymeric pigments of young red wine . Routine
detection is based on measurement of UV-Vis absorption
with a diode array detector (DAD) [39, 40]. Coupling of
absorptiometric and fluorometric detectors in series allows a
better discrimination between fluorescent and nonfluorescent
co-eluting compounds [41-43]. Further enhancing selectivity
and sensitivity for the determination of certain polyphenols
requires the application of other detection techniques, such
as, electrochemistry  and chemiluminescence .
HPLC currently represents the most popular technique
employment of mass spectrometry (MS) often used in
combination with UV detection [45-47]. Tandem mass
spectrometry (MS/MS) is irreplaceable method for the
identification of analytes which standard compounds are not
commercially available. Thus, HPLC/MS/MS has been used
The exact identification of polyphenolic structures allows
recently for identification of hydroxycinnamic acid–tartaric
acid esters in wine . HPLC method coupled with mass
spectrometry and electrospray ionization (ESI) has allowed
analysis of seven isomers of resveratrol dimers and three of
their analogues in wine grapes . Besides, same method is
used for the determination of several group polyphenols
(stilbenes, phenolic acids and their derivates, flavonols,
flava-3-ols and anthocyanins) in red wine [50-52]. Matrix-
assisted laser desorption/ionization (MALDI), as ionization
method in mass spectrometry, has been used for the analysis
of anthocyanins . Resveratrol dimer, cis-?-viniferin was
isolated by means of centrifugal partition chromatography
(CPC), a method that allows separation of analytes inherent
in very small concentration in sample. This resveratrol dimer
was structurally identified by means of MALDI and
hydrogen-1 nuclear magnetic resonance (1H NMR) spectra
. Liquid chromatography with mass spectrometry using
atmospheric pressure ionisation (APCI) in negative mode
allows identification of large number of polyphenols in wine
with high sensitivity .
Only few GC/MS analytical methods have been
developed to characterize and quantify phenolic compounds
in wine since that method requires previous derivatization to
the volatile compounds and mass-spectrometric detection in
the selective ion-monitoring mode (GC/MS-SIM). In study
of Minuti et al. , 22 polyphenols have been determined
using that method.
Capillary electrophoresis (CE) is rapidly developing
analytical tool successfully used for analysis of polyphenols
in red and white wine with an opportune sample
preconcentration step. Thus, determination of some
polyphenols was carried
electrophoresis (CZE) in solid phase extract (SPE) of wine
 or in extracts obtained by liquid/liquid extraction of
wine . Micellar electrokinetic capillary chromatography
(MECC) is a modification of CZE that has utility to separate
neutral analytes under the influence of an electric field. That
method was successfully applied for the separation of
polyphenols in wine with good resolution, high efficiency,
and low analysis time [58, 59].
out with capillary zone
HEALTH EFFECT OF WINE
compounds present in wine, especially red wines, are
associated with beneficial effects of wine consumption on
human health. These phytochemicals mostly may act as
antioxidants and/or modulation of enzymatic activities.
As mentioned earlier, many of the polyphenolic
Antioxidant Activity of Wine Polyphenols
specific metabolic purposes, and they can damage biological
structures such as proteins, lipids, or DNA. Humans possess
a wide array of antioxidant physiological defences to
scavenge free radicals, chelate metal ions involved in their
formation and repair damage. Intake of antioxidant
nutritients such as vitamins and polyphenols contribute to
these defences as well.
Free radicals are constantly generated in our body for
directly related to polyphenolic content [60, 61]. Since the
Red wines exhibit strong antioxidant activity that is
Innovations of Analysis and Health Effects of Wine Polyphenols
Mini-Reviews in Medicinal Chemistry, 2011, Vol. 11, No. 13 5
contribution of each polyphenol to the antioxidant activity of
wines is different, in literature exist contrast data about
correlation between the antioxidant activity and total
polyphenolc contents of wine. Thus, study of Di Majo et al.
 showed that high antiradical activity might have sorts of
wine rich of polyphenols, and sorts of wine with lower
amount of polyphenols. In study of de Quirós et al. , best
correlation between flavonols and antioxidant activity of
white wine was obtained. Red wines have higher antioxidant
activity than the white wine due to presence of anthocyanins
that are responsible for the colour of the red wine .
Recent study about relationship of the individual
polyphenols and antioxidant activity of red wine showed the
high correlation of total flavonols (r = -0.89) and acylated
anhocyanins (r = 0.70) with the overall antioxidant capacity
of wine . As wine ages, increases degree of
polymerization of polyphenols that resulted in an inrease in
antioxidant activity of wine .
Relationship Between Structure and Antioxidant Activity of
activity is different because biological activity of
polyphenols is deeply related with their chemical structure.
The radical-scavenging activity of flavonoids depends on the
molecular structure and the substitution pattern of hydroxyl
groups, i.e., on the availability of phenolic hydrogens and on
the possibility of stabilization of the resulting phenoxyl
radicals via hydrogen bonding or by expanded electron
delocalization. Although antioxidant activity of polyphenols
is associated with various mechanisms, the elevated
reactivity of polyphenolics towards active free radicals is
considered as the most principle mechanism. Their reducing
properties as hydrogen or electron donor predict their
potential as free- radical scavengers. For example,
polyphenols scavenging lipid alkoxyl and peroxyl radical by
acting as chain breaking antioxidans, as hydrogen donors
The contribution of each polyphenol to the antioxidant
depends on molecular structure and the substitution pattern
of free hydroxyl groups on the flavonoid skeleton, the
antioxidant activity of polyphenols can largely be predicted
on the basis of their chemical structure. Antioxidant and
antiradical activities of flavonoids are related to the presence
of: ortho 3',4'-dihydroxy moiety in the B-ring; C2-C3 double
bond in the C-ring in conjugation with a 4-oxo function in
the C ring; and meta 5,7-dihydroxy arrangements in the A
ring (Fig. 3).
Considering the radical scavenging activity of flavonoids
Fig. (3). Structural features of flavonoids with high antioxidant
esters an important parameter is the number of hydroxyl
groups in the molecule and the presence of steric hindrance.
The substituent that causes a steric hindrance is a carboxylate
group in benzoic acid because it has negative influence on
the H-donating abilities of hydroxy benzoates. Hence,
hydroxybenzoic acids are
hydroxycinnamic acids with equal positions of hydroxyl
groups in the ring .
For the antioxidant activity of phenolic acids and their
less effective than
attempts to establish a correlation between various molecular
descriptors of a set of molecules derived from chemical
structure with their experimentally obtained biological
activity. Thus, QSAR provides an estimation or even
prediction of antioxidant activity of untested polyphenols, as
well as, leads to understanding of mechanisms of action.
There are many numerical descriptors available in chemistry,
including topological indices, 3D descriptors, quantum
chemical indices, and physicochemical
associated with the molecular structure in QSAR researches.
Among them, topological indices are the most popular since
they can effectively characterize molecular size, branching,
and variation in molecular shapes .
Quantitative structure activity relationships (QSAR)
order to estimate antioxidant activity of wine polyphenols
using descriptors and various physicochemical parameters
derived from two-dimensional (2D) and three-dimensional
(3D) representations of chemical structure. The derived
QSAR models indicate that a size and shape of molecules, as
well as steric properties, play an important role in the
antioxidant activity of polyphenols . QSAR study of
anthocyanins, anthocyanidins, and catechins as inhibitors of
lipid peroxidation using 3D descriptors have indicated about
importance of three-dimensional distribution of atomic mass
in the molecule . The importance of presence or absence
of the 3,4-diOH and/or 3-OH group for radical scavenging
activity of poyphenols was confirmed recently by
computation of bond dissociation enthalpies and selecting
the minimal of all values relating to flavonoid OH groups
Recently, QSAR have been used to develop models in
Antioxidant Activity of Wine and Influence of Wine
Polyphenols on Cardiovascular Disease
reduced incidence of hearth disease, first antioxidant effect
of flavonoids is related with their inhibition of low-density
lipoprotein (LDL) oxidation that might be central in the
development of cardiovascular diseases and atherosclerosis.
The antioxidant activity of different wines toward LDL
oxidation is not a property of a single compound because of
possible effects of synergism and antagonism between
certain polyphenols .
Since wine consumption have been associated with
different classes of polyphenols were extracted from the
same wine and the antioxidant capacity of the different
fractions was tested. The anthocyanin fraction was found
most effective both in scavenging reactive oxygen species
and in inhibiting lipoprotein oxidation, as well as platelet
aggregation [73, 74]. Some authors emphasised the
To discriminate the action of the various phenols in wine,
6 Mini-Reviews in Medicinal Chemistry, 2011, Vol. 11, No. 13 V. Rastija
importance of resveratrol, which reduces LDL oxidation in
wine in retarding atherogenesis were proposed as an
explanation for the “French Paradox”. Epidemiological study
of Renaud and Lorgeril  demonstrated that in the certain
parts of France CHD mortality was low despite a relatively
high fat intake. Moderate consumption of wine was one
dietary factor that could partly explain this low morbidity
and mortality from CHD.
The antioxidant properties of phenolic compounds in red
polyphenols alone or in association with ethanol are able to
prevent cardiac hypertrophy and production of reactive
oxygen species. Results of study also indicate about
differential mechanisms of polyphenols and ethanol in
regulating blood pressure.
Study of Al-Awwadi et al.  showed that red wine
mainly through nitric oxide-dependent mechanism . The
NO-dependent vasorelaxation by the red wine-derived
phenolic compounds was associated with the inhibition of
smooth muscle phosphodiesterases .
Wine polyphenols also exhibit vasorelaxing effects,
able to reduce blood pressure in normo- and hypertensive
rats . The amplitude of vasorelaxation changed as a
function of the variability of wine constituents according to
the grape varieties, cultivar, and methods for obtaining wine
. In recent study, interrelationship between antioxidative
capacity and vasodilatory activity, two potentially beneficial
biological effects, of nine phenolic acids from wine was
investigated. A negative correlation between in vitro
antioxidative and vasodilatory activity of the tested phenolic
acids was found. This is the best illustrated by poor
vasodilatory activity of gallic acid, the strongest antioxidant
among the tested phenolic acids. Generally, phenolic acids
appear to be weaker vasodilators than antioxidants. QSAR
study indicates that the increase in the number of hydroxyl
groups in the phenyl ring is unfavourable for vasodilatory
effect, as opposed of antioxidative activity of phenolic acid
In vivo red wine-derived polyphenolic compounds were
Other Health Effects of Wine Polyphenols
Anti-Cancerogenic Properties of Wine Polyphenols
studies describing the potential cancer chemopreventive
activities of red wine polyphenols, protective effects have
not been assigned to a specific fraction or compound [82,
83]. Therefore, to investigate the cancer chemopreventive
effects of red wine polyphenols as total extract or fractions
are of importance . Soleas et al.  suggested that
trans-resveratrol might be the most effective anticancer
polyphenol present in red wine since is absorbed much more
efficiently than (+)-catechin and quercetin in humans after
Although a large body of literature has been devoted to
 and cell death of a human leukaemia cell by
polyphenols extracted from red wine . Also, the red wine
polyphenols have been reported to inhibit the process of
colon carcinogenesis  and induce of apoptosis of colon
Recent articles report about inhibition of proliferation
cancer cells . Anti-proliferative effect on the growth of
the human colon cancer cell of red wine has been attributed
to the effect of resveratrol .
properties, new studies have found that excessive
consumption of alcohol increases the risk of several cancers.
For example, in vitro and in vivo studies demonstrated that
procyanidin B dimers in red wine and grape seeds could be
used as chemopreventive agents against breast cancer by
suppressing in situ estrogen biosynthesis . While some
studies warning that wine consumption increases a woman's
risk of breast cancer, other report that only high alcohol
consumption increases breast cancer risk. Recent case-
control study among a population in Southern France
showed that low and regular wine consumption does not
increase breast cancer risk. Moreover, the risk associated
with women who consumed approximately one drink of
wine per day (10–12 g of ethanol/d) decreased significantly
when compared with the risk associated with non–wine
drinkers or sporadic wine drinkers. However, above 12 g/d
of wine consumption increased the risk of breast cancer but
the association was non-significant .
Although wine polyphenols have cancer-fighting
Hormonal Activity of Wine Polyphenols
phytoestrogen. It is possible that its estrogenic activity is
conditioned by structural similarity to synthetic estrogen,
diethylstilbestrol. Resveratrol binds to the estrogens receptor
and activates the transcription of estrogen-responsive target
genes. Several additional hydroxystilbenes, including
diethylstilbestrol and piceatannol, were tested, and all
showed estrogens receptor agonism or partial agonism, but
superagonism was specific to resveratrol. These results
indicate that superagonism is not a general property of
hydroxystilbene estrogens, but a specific property of
resveratrol, dependent on the number and position of the
hydroxyl substituent. However, finding that resveratrol
stimulates the growth of human breast cancer cells may limit
the circumstance under which it can be used safely. But,
estrogenic activity of resveratrol could be basis for the
structure-activity studies for development of more selective
estrogens receptor, which could be useful as a therapeutic
drug [93, 94].
Studies have shown that resveratrol acts as
Antidiabetic Activity of Wine Polyphenols
inherited or acquired deficiency in insulin secretion and by
decreased responsiveness of the organs to secreted insulin,
which results in increased blood glucose levels. The long-
term manifestations of this deficiency cause organ damage
with serious effects, such as retinopathy, neuropathy, and
Diabetes mellitus is a chronic disease caused by an
that polyphenol extract from red wine reduces glycemia and
decreases food intake and body growth in diabetic and non-
diabetic animals. Same effect was also reached with ethanol
alone or in combination with polyphenols .
Study of antidiabetic activity of the red wine has shown
or classes of polyphenols have inhibitory activity against key
There is increasing evidence that individual polyphenols
Innovations of Analysis and Health Effects of Wine Polyphenols
Mini-Reviews in Medicinal Chemistry, 2011, Vol. 11, No. 13 7
enzymes of dietary carbohydrate digestion in humans, such
as ?-glucosidase and ?-amylase. Strawberry and raspberry
extracts were more effective ?-amylase inhibitors than
blueberry, blackcurrant, or red cabbage. A contrary, ?-
glucosidase was more readily inhibited by blueberry and
blackcurrant extracts since inhibitory agents against activity
of this enzyme proved to be diacylated anthocyanins.
Extracts that contain tannins (red grape, red wine, green tea,
raspberry, and strawberry) were more effective ?-amylase
inhibitors than other extracts . Tannic acid and the
tannin-rich nonalcoholic components of red wine have been
shown to reduce serum glucose levels after starch-rich meals
in a study of patients with non-insulindependent diabetes
mellitus . Results of recent study showed that grape seed
procyanidin extract stimulates glucose uptake in insulin
resistant adipocytes with higher capacity than insulin. Higher
dose than 25 mg/kg body weight per day could have a
negative effect on glucose homeostasis, what indicating
about importance of carefully prescribing doses of natural
drugs in diabetes treatment .
Wine Polyphenols in Prevention of Cataracta Formation
and Retinal Degenerative Diseases
cataracta, one of the principal causes of blindness in world
population. Hence, dietary antioxidants such as vitamin C,
vitamin E, and carotenoids prevent the cataracta formation in
humans. Also, procyanidins, which are present in their
largest amount in wine and grape seeds, have been reported
that retard the progression of cataracta formation by their
antioxidative action in hereditary cataractous rats .
Oxidative stress is common mechanism of formation of
progression of many retinal diseases, including degenerative
diseases such as age-related macular degeneration (AMD)
and hyperproliferative disorders such as vitreoretinopathy.
Dietary strategies that limit oxidation in the retina may
therefore be important in preventing the development of
these diseases. Epidemiological evidence suggests that
moderate wine consumption and antioxidant-rich diets may
protect against age-related macular degeneration, the leading
cause of vision loss among the elderly. Study of King et al.
 was demonstrated that resveratrol, a red wine
polyphenol, is responsible for the health benefits of moderate
red wine consumption on retinal diseases in such a manner
that inhibits intracellular oxidation and proliferation of
retinal pigment epithelium (RPE) cell . Recent
investigation by Sheu and Wu suggested that resveratrol also
protect RPE cell from ultraviolet irradiation .
Oxidative stress is also thought to contribute to the
Neuroprotective Effects of Wine Polyphenols
might reduce the risk of neurodegenerative diseases such as
Alzheimer’s disease and dementia [101-103]. Majority of
neurodegenerative diseases are associated to the oxidative
stress. Neuroprotective effects of polyphenols are partly
based on their antioxidant activities . Recent study of
neuroprotective properties of Spanish red wine and its
isolated polyphenols has demonstrated that quercetin and
procyanidins are the most active polyphenols . Another
study was found that trans-resveratrol affects neuropro-
Few studies have indicated that moderate wine intake
tective through its ability to inhibit fast transient of voltage-
activated K+ currents in rat hippocampal neurons, which
have been implicated in neuronal apoptosis .
Antimicrobial Effect of Wine Polyphenols
individual flavonids against bacterias, protozoas, and fungus.
They have activating or inhibiting effects on microbial
growth and metabolism .
Recent results indicate about high antimicrobial potential
of natural extract of grape skins. Therefore, the antimicrobial
activity of grape skin extracts of 14 Vitis vinifera varieties
was confirmed against Gram-positive (Staphylococcus
aureus, Bacillus cereus) and Gram-negative bacteria
(Escherichia coli, Salmonella infantis, Campylobacter coli)
. Also, many recent studies reported about the
antimicrobial activities of wines and wine extracts against
various pathogens. For example, antimicrobial activity of red
wine and white wine polyphenolics extracts was confirmed
against: Staphylococcus aureus, Escherichia coli, Candida
albicans [109, 110], Pseudomonas savastanoi ,
Campylobacter jejuni , Flavobacterium , and
Lysteria monoxytogenes . Red wines and especially
their active fraction that contains resveratrol showed good
activity against Helicobacter pylori .
In model stomach systems conatining food and synthetic
gastric fluid, wine had a little effect on E. coli, but great on
Salmonella typhimurium  and Campylobacter jejuni
. Given studies showed that the ingestion of wine
during a meal may greatly diminish the quantity of those
bacteria and thus lowering the risk of the infection.
Antibacterial activity of wine could be rightly attributed
to the polyphenols since that was confirmed that antibacterial
activity of nonvolatile fraction (containing polyphenols) of
wine is more effective than the volatile fraction (containing
alcohol) . Besides, the lower antimicrobial activity of
certain wine it is related with its lower polyphenolic
Numerous studies have evidenced about effects of
Anticariogenic Action of Wine Polyphenols
besides exerting antibacterial activity, strongly interferes
with Streptococcus mutans adhesion to saliva-coated
hydroxyapatite (sHA) beads, promotes its detachment from
sHA, and powerfully inhibits in vitro biofilm formation. The
main components, responsible for such activities, were found
to be proanthocyanidins. The ability of red wine to inhibit ex
vivo S. mutans biofilm formation on the occlusal surface of
natural human teeth also was demonstrated .
In vitro findings shows that dealcoholised red wine,
Harmful Effects of Wine Consumption on Health
health, there is a numerous negative sides of wine
consumption. The most harmful effect is associated with
excessive wine drinking that may leads to an alcohol
dependency syndrome and implies an increased risk of large
number of physical and mental illness. High doses of alcohol
(? 5 drinks a day) are associated with a death and CHD
, especially for middle-aged and older adults .
Study of Bleich et al.  has evidenced that elevated
Besides an above mentioned positive effects of wine on
8 Mini-Reviews in Medicinal Chemistry, 2011, Vol. 11, No. 13 V. Rastija
levels of homocystein in social drinkers are associated with
an increased risk of cardiovascular diseases, which is the
contradictory to the “French paradox”.
Epidemiological Study of Myocardial Infarction (PRIME)
showed that favourable effects of wine on the incidence of
ischaemic heart disease or on mortality rates in France are
consistent with those found in the other countries. Namely,
moderate wine consumption is associated with people of
higher socioeconomic status in whome health behaviour is
Analysis of cohort data from the Prospective
number of diseases, such as: liver diseases , chronic
pancreatitis , and oesophageal carcinoma .
Alcohol consumption is one of the risk factor for the breast
cancer among postmenopausal women . Grønbæk
recently reviewed the negative effects of alcohol on health,
such as dementia, breast cancer, colorectal cancer, cirrhosis,
and upper digestive tract cancer . Pregnant women
should abstain from drinking wine
consumption is associated with increased risk of birth defect,
such as cryptorchidism and metal health disorder .
Regular excessive wine drinking provokes a large
Bioavailability of Wine Polyphenols
absorbed and can be measured in plasma. Despite their
powerful biologic activities conducive to protection against
atherosclerosis, cancer and
demonstrated in vitro, there is considerable doubt whether
the polyphenolic constituents present in wine are effective in
vivo. Polyphenols are known
biotransformations during digestion and absorption and
during the post-absorptive metabolism. This pre- and post-
absorptive metabolism has a considerable influence on the
antioxidant capacity of specific compounds, and therefore
the biological properties of wine polyphenols depend on
their bioavailability. The polyphenols that are most well
absorbed in humans are isoflavones, gallic acid, catechins,
flavanones, and quercetin glucosides. The least well
absorbed the proanthocyanidins, and anthocyanidins [72,
The biological activity of a compound is plausible if it is
to be subject to
low (100 nM to 1 μM), but those doses were sufficient for
the biological effects on coagulations and platelet
aggregation. Possible mechanisms underlying the activity of
such low quantities are the accumulation of resveratrol in the
organs, such as heart, liver and lung, as well as, binding of
resveratrol to albumin that could be natural polyphenol
reservoir, and might play a crucial role in the distribution
and bioavailability of polyphenols .
Blood level resveratrol after chronic consumption is very
compounds present in wine or ingested with the food. Thus,
synergy amongst the resveratrol, caffeic acid, and catechin,
which ensures biological activity, has been evidenced .
Interactions among polyphenols may influence their kinetics
and metabolism, and thereby increase theirs bioavailability.
Moreover, polyphenols may interact with other
bioavailability of polyphenols, there is lot of unsolved
Despite of existing results of researches about
questions, such as: the effect of flavonoid conjugation on the
rate of the intestinal absorption; interaction with other
nutrients; liver metabolism and resecretion of polyphenols in
bile, role of the colonic microflora. Further research on
polyphenol bioavailability must allows us to correlate
polyphenol intakes with one or several accurate measures of
bioavailability (such as concentrations of key bioactive
metabolites in plasma and tissues), and with potential health
effects in epidemiologic studies.
with several health benefits. These effects are associated
with polyphenolic compounds that are found in wine. Due to
numerous evidences about health promoting actions of wine
polyphenols, a significant number of publications over the
past ten years have dealt with the analysis of those
compounds in wine, including development of extraction,
separation and detection methods. Although today we know
lot about the polyphenolic components of wine, there is
insufficient data about contribution of each polyphenol to the
biological activity of wines and which is the most important.
Also, very little researches have been done on the
metabolism and biological activities of phenolics at cellular,
molecular and biochemical levels. Efficiency of wine
polyphenols highly depends on their bioavailability,
therefore, further ADME
Metabolism, Excretion) studies are of great importance.
Regular moderate wine consumption has been associated
on physical and mental health, and may leads to alcoholism,
wine should be consumed moderately.
Since regular excessive wine drinking affects adversely
awarded by the Ministry of Science, Education, and Sport of
the Republic of Croatia.
This work was supported by grant no. 079-0000000-3211
ADME = Adsorption, Distribution, Metabolism,
APCI = atmospheric pressure chemical ionization
CE = capillary electrophoresis
CZE = capillary zone electrophoresis
CPC = centrifugal partition chromatography
CHD = coronary heart disease
DAD = diode array detector
ESI = electrospray ionization
GC = gas chromatography
HPTLC = high performance thin layer
HPLC = high-performance liquid chromatography
1H NMR = hydrogen-1 nuclear magnetic resonance
LDL = low-density lipoprotein
Innovations of Analysis and Health Effects of Wine Polyphenols
Mini-Reviews in Medicinal Chemistry, 2011, Vol. 11, No. 13 9
MALDI = matrix-assisted laser desorption/ionization
MECC = micellar electrokinetic capillary
NMR = nuclear magnetic resonance
QSAR = quantitative structure activity relationships
RP-HPLC = reverse phase high-performance liquid
RP-TLC = reversed-phase thin-layer chromatographic
SIM = selective ion-monitoring mode
SPE = solid phase extract
MS/MS = tandem mass spectrometry
TLC = thin-layer chromatography
UV = ultraviolet
RPE = retinal pigment epithelium
sHA). = saliva-coated hydroxyapatite
Dominé, A. Wine, Könemann Tandem Verlag: Königswinter, 2003.
Renaud, S.C.; de Lorgeril M. Wine, alcohol, platelets, and the
French paradox for coronary heart disease. Lancet, 1992, 339,
Fremont, L.; Belguendouz, S.; Delpal, S. Antioxidant activity of
resveratrol and alcohol-free wine polyphenols related to LDL
oxidation and polyunsaturated fatty acids. Life Sci., 1999, 64,
Tunstall-Pedoe, H.; Kuulasmaa, K.; Mahonen, M.; Tolonen, H.;
Ruokokoski, E.; Amouyel, P. Contribution of trends in survival and
coronary-event rates to changes in coronary heart disease mortality:
10-year results from 37 WHO MONICA project populations.
Monitoring trends and determinants in cardiovascular disease.
Lancet, 1999, 353, 1547-57.
Rodríguez Vaquero, M.J.; Alberto, M.R.; Manca de Nadra, M.C.
Antibacterial effect of phenolic compounds from different wines.
Food Control, 2007, 18, 93-101.
Konowalchuk, J.; Speirs, J.I. Virus inactivation by grapes and
wines. Appl. Environ. Microbiol., 1976, 32, 757-763.
Soleas, G.J.; Grass, L.; Josephy, P.D.; Goldberg, D.M.; Diamandis,
E.P. A comparison of the anticarcinogenic properties of four red
wine polyphenols. Clin. Biochem., 2002, 35, 119-124.
Carluccio, M.A.; Siculella, L.; Ancora, M.A.; Massaro, M.;
Scoditti, E.; Storelli, C.; Visioli, F.; Distante, A.; De Caterina, R.
Olive oil and red wine antioxidant polyphenols inhibit endothelial
activation: antiatherogenic properties of Mediterranean diet
phytochemicals. Arterioscler. Thromb. Vasc. Biol., 2003, 23, 622-
de Lorimier, A.A. Alcohol, Wine, and Health. Am. J. Surg., 2000,
Preys, S.; Mazerolles, G.; Courcoux, P.; Samson, A., Fisher, U.;
Hanafi, M.; Bertrand, D.; Cheynier, V. Relationship between
polyphenolic composition and some sensory properties in red wines
using multiway analyses. Anal. Chim. Acta, 2006, 563, 126–136.
Rastija, V.; Mornar, A.; Jasprica, I.; Sre?nik, G.; Medi?-?ari?, M.
Analysis of phenolic components in Croatian red wine by thin-
layer chromatography. J. Planar. Chromatogr.-Mod. TLC, 2004,
?eruga, M.; Novak, I.; Jakobek, L. Determination of polyphenols
content and antioxidant activity of some red wines by differential
pulse voltammetry, HPLC and spectrophotometric methods. Food
Chem. 2011, 124, 1208-1216.
Pazourek, J.; Gajdo?ová, D.; Spanilá, M.; Farková, M.; Novotná,
K.; Havel, J. Analysis of polyphenols in wines: Correlation
between total polyphenolic content and antioxidant potential from
photometric measurements. Prediction of cultivars and vintage
from capillary zone electrophoresis fingerprints using artificial
neural network. J. Chromatogr. A, 2005, 48-54.
Ko?ir, I. J.; Kidri?, J. Use of modern nuclear magnetic resonance
spectroscopy in wine analysis: determination of minor compounds.
Anal. Chim. Acta, 2002, 458, 77-84.
Burns, J.; Gardner, P.T.; Matthewes, D.; Duthie, G.G.; Lean,
M.E.J.; Crozier, A. extraction of phenolics and changes in
antioxidant activity of red wines during vinification. J. Agric. Food
Chem., 2001, 49, 5797-5808.
Budi?-Leto, I.; Lovri?, T. Content during fermentation and ageing
of white wines Po?ip and Rukatac. Food Technol. Biotechnol.,
2002, 40, 221-225.
Flamini, R. Mass spectrometry in grape and wine chemistry. Part I:
Polyphenols. Mass Spectrom. Rev., 2003, 22, 218-250.
Gutiérrez, I.H.; Lorenzo, E.S.-P.; Espinosa, A.V. Phenolic
composition and magnitude of copigmentation in young and shortly
aged red wines made from the cultivars, Cabernet Sauvignon,
Cencibel, and Syrah. Food Chem., 2005, 92, 269-283.
Kallithraka, S.; Tsoutsouras, E.; Tzourou, P.; Lanaridis, P.
Principal phenolic compounds in Greek redwine. Food Chem.,
2006, 99, 784–793.
Xu, C.; Zhang, Y.; Cao, L.; Lu, J. Phenolic compounds and
antioxidant properties of different grape cultivars grown in China.
Food Chem., 2010, 119, 1557–1565.
Anastasiadi, M.; Zira, A.; Magiatis, P.; Haroutounian, S.A.;
Skaltsounis, A.L.; Mikros, E. 1H NMR-based metabonomics for the
classification of Greek wines according to variety, region, and
vintage. Comparison with HPLC data. J. Agric. Food Chem., 2009,
Bergqvist, J.; Dokoozlian, N.; Ebisuda, N. Sunlight exposure and
temperature effects on berry growth and composition of Cabernet
Sauvignon and Grenache in the Central San Joaquin Valley of
California. Am. J. Enol. Vitic., 2001, 52, 1-7.
Mc Donald, M.; Hughes, M.; Burns, J.; Lean, M.E.J.; Matthews,
D.; Crozier, A. Survey of the free and conjugated myricetin and
quercetin content of red wines of different geographical origins. J.
Agric. Food Chem., 1998, 46, 368–375.
Mateus, N.; Proença, S.; Ribeiro, P. Machado, J.M.; De Freitas, V.
Grape and wine polyphenolic composition of red Vitis vinifera
varieties concerning vineyard altitude. Cienc. Technol. Alliment.,
2001, 3, 102-110.
Rastija, V.; Sre?nik, G.; Medi?-?ari?, M. Polyphenolic composition
of Croatian wines with different geographical origins. Food Chem.,
2009, 115, 54-60.
Delgado, R.; Martín, P.; del Álamo, M.; González, M.-R. Changes
in the phenolic composition of grape berries during ripening in
relation to vineyard nitrogen and potassium fertilisation rates. J.
Sci. Food Agric., 2004, 84, 623-630.
Kova?, V.; Alonso, E.; Bourzeix, M.; Revilla, E. Effect of several
enological practices on the
proanthocyanidins of red wines. J. Agric. Food Chem., 1992, 40,
Spranger, M.I.; Clímaco, M.C.; Sun, B.; Eiriz, N.; Fortunato, C.;
Nunes, A.; Leandro, M.C.; Avelar, M. L.; Belchior, A. P.
Differentiation of red winemaking technologies by phenolic and
volatile composition. Anal. Chim. Acta, 2004, 513, 151-161.
Makris, D.P.; Kallithraka, S.; Kefalas, P. Flavonols in grapes, grape
products and wines: Burden, profile and influential parameters. J.
Food Compos. Anal., 2006, 19, 396-404.
Sanza, M.A.; Domínguez, I.N.; Cárcel, L.M.C.; Gracia, L.G.
Analysis for low molecular weight phenolic compounds in a red
wine aged in oak chips. Anal. Chim. Acta, 2004, 513, 229-237.
Caridi, A.; Cufari, A.; Lovino, R.; Palumbo, R.; Tedesco, I.
Influence of yeast on polyphenol composition of wine. Food
Technol. Biotechnol., 2004, 42, 37-40.
Medi?-?ari?, M.; Rastija, V.; Boji?, M. Recent advances in the
application of high-performance liquid chromatography in the
analysis of polyphenols in wine and propolis. J. AOAC Int., 2011,
Sun, B.; Leandro, C., da Silva, J.M.R.; Spranger, I. Separation of
grape and wine proanthocyanidins according to their degree of
polymerization. J. Agric. Food Chem., 1998, 1390-1396.
Rastija, V.; Medi?-?ari?, M. Chromatographic methods for the
analysis of polyphenols in wines, Kem. Ind., 2009, 58, 121-128.
content of catechins and
10 Mini-Reviews in Medicinal Chemistry, 2011, Vol. 11, No. 13 V. Rastija
 Cimpoiu, C.; Hosu, A.; Briciu, R.; Miclaus, V. Monitoring of the
wine origin by reversed-phase thin-layer chromatography. J.
Planar. Chromatogr.-Mod. TLC, 2007, 20, 407-410.
Lambri, M., Jourdes, M.; Glories, Y.; Saucier, C. High
performance thin layer chromatography (HPTLC) analysis of red
wine pigments. J. Planar. Chromatogr.-Mod. TLC, 2003, 16, 88-
Lucena, A.P.S.; Nascimento, R.J.B.; Maciel, J.A.C.; Tavares, J.X.;
Barbosa-Filho, J.M.; Oliveira, E.J. Antioxidant activity and
phenolics content of selected Brazilian wines. J. Food Compos.
Anal., 2010, 23, 30-36.
Versari, A.; Boulton, R.B.; Parpinello, G.P. A comparison of
analytical methods for measuring the color components of red
wines. Food Chem., 2008, 106, 397-402.
Vinkovi? Vr?ek, I.; Boji?, M.; ?untar, I.; Menda?, G.; Medi?-?ari?,
M. Phenol content, antioxidant activity and metal composition of
Croatian wines deriving from organically and conventionally
grown grapes. Food Chem., 2011, 124, 354-361.
Miti?, M.N.; Obradovi?, M.V.; Grahovac, Z.B.; Pavlovi?, A.N.
Antioxidant capacities and phenolic levels of different varieties of
Serbian white wines. Molecules, 2010, 15, 2016-2027.
Gómez-Alonso, S.; García-Romero, E.; Hermosín-Gutiérrez, I.
HPLC analysis of diverse grape and wine phenolics using direct
injection and multidetection by DAD and fluorescence. J. Food
Compos. Anal., 2007, 20, 618-626.
Granato, D.; Katayama, F.C.U.; de Castro, I.A. Phenolic
composition of South American red wines classified according to
their antioxidant activity, retail price and sensory quality. Food
Chem., In press, available
de Souza Dias, F.; Lovillo, M.P.; Barroso, C.G.; David, J.M.
Optimization and validation of a method for the direct
determination of catechin and epicatechin in red wines by
HPLC/fluorescence. Microchem. J., 2010, 96, 17-20.
Mattila, P.; Astola, J.; Kumpulainen, J. Determination of flavonoids
in plant material by HPLC with diode-array and electro-array
detections. J. Agric. Food Chem., 2000, 38, 5834-5841.
Bellomarino, S.A.; Conlan, X.A.; Parker, R.M.; Barnett, N.W.;
Adams, M.J. Geographical classification of some Australian wines
by discriminant analysis using
chemiluminescence detection. Talanta, 2009, 80, 833-838.
González-Neves, G.; Gil, G.; Barreiro, L.; Favre, G. Pigment
profile of red wines cv. Tannat made with alternative winemaking
techniques. J. Food Compos. Anal., 2010, 23, 447-454.
Gris, E.F.; Mattivi, F.; Ferreira, E.A.; Vrhovsek, U.; Pedrosa, R.C.;
Bordignon-Luiz, M.T. Proanthocyanidin profile and antioxidant
capacity of Brazilian Vitis vinifera red wines. Food Chem., 2011,
Buiarelli, F.; Coccioli, F. Merolle, M.; Jasionowska, R.;
Terracciano, A. Identification of hydroxycinnamic acid–tartaric
acid esters in wine by HPLC–tandem mass spectrometry. Food
Chem., 2010, 12, 827-833.
Kong, Q.J.; Ren, X.Y.; Hu, N.; Sun, C.R.; Pan, Y.J. Identification
of isomers of resveratrol dimer and their analogues from wine
grapes by HPLC/MSn and HPLC/DAD-UV. Food Chem., 2011,
Ivanova, V.; Dörnyei, Á.; Márk, L.; Vojnovski, B.; Stafilov, T.;
Stefova, M.; Kilár, F. Polyphenolic content of Vranec wines
produced by different vinification conditions. Food Chem., 2011,
Vergara, C.; Mardones, C.; Hermosin-Gutierrez, I.; von Baer, D.
Comparison of high-performance liquid chromatography separation
of red wine anthocyanins on a mixed-mode ion-exchange reversed-
phase and on a reversed-phase column. J. Chromatogr. A, 2010,
Nixdorf, S.L.; Hermosin-Gutiérrez, I. Brazilian red wines made
from the hybrid grape cultivar Isabel: Phenolic composition and
antioxidant capacity. Anal. Chim. Acta, 2010, 208-215.
Muñoz-Espada, A.C.; Wood, K.V.; Bordelon, B.; Watkins, B. A.
Anthocyanin quantification and radical scavenging capacity of
Concord, Norton, and Marechal Foch grapes and wines. J. Agric.
Food Chem., 2004, 52, 6779-6786.
Amira-Guebailia, H.; Valls, J.; Richard, T.; Vitrac, X.; Monti, J.-P.;
Delaunay, J.-C-; Mérillon,
online 1 May
HPLC with UV and
J.-M. Centrifugal partition
chromatography followed by HPLC for the isolation of cis-?-
viniferin, a resveratrol dimer newly extracted from a red Algerian
wine. Food Chem., 2009, 113, 320-324.
Bravo, M.N.; Silva, S.; Coelho, A.V.; Vilas Boas, L., Bronze, M.R.
Analysis of phenolic compounds in Muscatel wines produced in
Portugal. Anal. Chim. Acta, 2006, 563, 84-92.
Minuti, L.; Pellegrino, R.M.; Tesei, I. Simple extraction method
and gas chromatography–mass spectrometry in the selective ion
monitoring mode for the determination of phenols in wine. J.
Chromatogr. A, 2006, 1114, 263-268.
Minussi, R.C.; Rossi, M.; Bologna, L.; Cordi, L.; Rotilio, D.;
Pastore, G.M.; Durán, N. Phenolic compounds and total antioxidant
potential of commercial wines. Food Chem., 2003, 82, 409-416.
Rodríguez-Delgado, M.A.; Pérez, M.L.; Corbella, R.; González,
G.; García Montelongo, F.J. Optimization of the separation of
phenolic compounds by micellar
chromatography. J. Chromatogr. A, 2000, 871, 427-438.
Sun, Y.; Fang, N.; Chen, D.D.Y.; Donkor, K.K. Determination of
potentially anti-carcinogenic flavonoids in wines by micellar
electrokinetic chromatography. Food Chem., 2008, 106, 415-420.
Valdez, L.B.; Álvarez, S.; Zaobornyj, T.; Boveris, A. Polyphenols
and red wine as antioxidants against peroxynitrite and other
oxidants. Biol. Res., 2004, 37, 279-286.
Di Majo, D.; La Guardia, M.; Giammanco, S.; La Neve, L.;
Giammanco, M. The antioxidant capacity of red wine in
relationship with its polyphenolic constituents. Food Chem., 2008,
Fernández-Pachón, M.S.; Villaño, D.; García-Parrilla, M.C.;
Troncoso, A.M. Antioxidant activity of wines and relation with
their polyphenolic composition. Anal. Chim. Acta, 2004, 513, 113-
Rodríguez-Bernaldo de Quirós, A.; Lage-Yusty, M.A.; López-
Hernández, J. HPLC-analysis of polyphenolic compounds in
Spanish white wines and determination of their antioxidant activity
by radical scavenging assay. Food Res. Int., 2009, 42, 1018-1022.
Roussis, I.G.; Lambropoulos, I.; Tzimas, P.; Gkoulioti, A.;
Marinos, V.; Tsoupeis, D.; Boutaris, I. Antioxidant activities of
some Greek wines and wine phenolic extracts. J. Food Compos.
Anal., 2008, 21, 614-621.
Alèn-Ruiz, F.; García-Falcón, M.S.; Pérez-Lamela, M.C.;
Martínez-Carballo, E.; Simal-Gándara, J. Influence of major
polyphenols on antioxidant activity in Mencía and Brancellao red
wines. Food Chem., 2009, 113, 53-60.
Rice-Evans, C.A.; Miller, N.J.; Paganga, G. Antioxidant properties
of phenolic compounds. Trends Plant Sci., 1997, 152-159.
Ami?, D.; Davidovi?-Ami?, D.; Be?lo, D.; Rastija, V.; Lu?i?, B.;
Trinajsti?, N. SAR and QSAR of the antioxidant activity of
flavonoids. Curr. Med. Chem., 2007, 14, 827-845.
Rice-Evans, C.; Miller, N.J.; Paganga, G. Structure-antioxidant
activity relationship of flavonoids and phenolic acids. Free Radical
Biol. Med., 1996, 20, 933-956.
Rastija, V; Medi?-?ari?, M. QSAR study of antioxidant activity of
wine polyphenols. Eur. J. Med. Chem., 2009, 44, 400-408.
Rastija, V., Medi?-?ari?, M. QSAR modeling of anthocyanins,
anthocyanidins and catechins as inhibitors of lipid peroxidation
using three-dimensional descriptors. Med. Chem. Res., 2009, 18,
Ami?, D.; Lu?i?, B., Kova?evi?, G.; Trinajsti?, N. Bond
dissociation enthalpies calculated by the PM3 method confirm
activity cliffs in radical scavenging of flavonoids. Mol. Divers.,
2009, 13, 27-36.
Sánchez-Moreno, C.; Jiménez-Escrig, A.; Saura-Calixto, F. LDL
oxidizability indexes in measurement of antioxidant activity in
selected Spanish wines. Nutr. Res., 2002, 22, 507-517.
Rivero-Pérez, M.D.; Muñiz,
Contribution of anthocyanin fraction to the antioxidant properties
of wine. Food Chem. Toxicol., 2008, 46, 2815-2822.
Ghiselli, A.; Nardini, M.; Baldi, A.; Scaccini, C. Antioxidant
activity of different phenolic fractions separated from an Italian red
wine. J. Agric. Food Chem., 1998, 46, 361-367.
Ou, H.-C.; Chou, F.-P.; Sheen, H.-M.; Lin, T.-M.; Yang, C.-H.;
Sheu, W. H.-H. Resveratrol, a polyphenolic compound in red wine,
protects against oxidized LDL-induced cytotoxicity in endothelial
cells. Clin. Chim. Acta, 2006, 364, 196-204.
 P.; Gonzálet-Sanjosé, M.L.
Innovations of Analysis and Health Effects of Wine Polyphenols
Mini-Reviews in Medicinal Chemistry, 2011, Vol. 11, No. 13 11
 Al-Awwadi, N.; Azay, J.; Poucheret, P.; Cassanas, G.; Krosniak,
M.; Auger, C.; Gasc, F.; Rouanet, J.-M.; Cros, G.; Teissèdre, P.L.
Red wine polyphenols alone or in association with ethanol prevent
hypertension, cardiac hypertrophy, and production of reactive
oxygen species in the insulin-resistant fructose-fed rat. J. Agric.
Food Chem., 2004, 52, 1008-1016.
Andriambeloson, E.; Kleschyov, A.L.; Muller, B.; Beretz, A.;
Stoclet, J.C.; Andriantsitohaina, R. Nitric oxide production and
polyphenols in rat aorta. Br. J. Pharmacol., 1997, 120, 1053-1058.
Agli, M.D.; Galli, G.V.; Vrhovsek, U.; Mattivi, F.; Bosisio, E. In
vitro inhibition of human cGMP-specific phosphodiesterase-5 by
polyphenols from red grapes. J. Agric. Food Chem., 2005, 53,
Diebolt, M.; Bucher, B.; Andriantsitohaina, R. Wine polyphenols
decrease blood pressure, improve NO vasodilatation, and induce
gene expression. Hypertension, 2001, 38, 159-165.
Burns, J.; Gardner, P.T.; O’Neil, J.; Crawford, S.; Morecroft, I.;
McPhail, D.B.; Lister, C.; Matthews, D.; MacLean, M.R.; Lean,
M.E.; Duthie, G.G.; Crozier, A. Relationship among antioxidant
activity, vasodilation capacity, and phenolic content of red wines.
J. Agric. Food Chem., 2000, 48, 220-230.
Mudni?, I.; Modun, D.; Rastija, V.; Vukovi?, J.; Brizic, I.;
Katalini?, V.; Kozina, B.; Medi?-?ari?, M.; Boban, M.
Antioxidative and vasodilatory effects of phenolic acids in wine.
Food Chem., 2010, 119, 1205–1210.
Yang, C.S.; Landau, J. M.; Huang, M.T.; Newmark, H.L. Inhibition
of carcinogenesis by dietary polyphenolic compounds. Annu. Rev.
Nutr., 2001, 21, 381-406.
Soleas, G.J.; Goldberg, D.M.; Grass, L.; Levesque, M.; Diamandis,
E.P. Do wine polyphenols modulate p53 gene expression in human
cancer cell lines? Clin. Biochem., 2001, 34, 415-420.
He, S.; Sun, C.; Pan; Y. Red wine polyphenols for cancer
prevention. Int. J. Mol. Sci., 2008, 9, 842-853.
Soleas, G.J.; Grass, L.; Josephy, P.D.; Goldberg, D.M.; Diamandis,
E.P. A comparison of the anticarcinogenic properties of four red
wine polyphenols. Clin. Biochem., 2002, 35, 119-124.
Sharif, T.; Auger, C.; Alhosin, M.; Ebel, C.; Achour, M.; Étienne-
Selloum, N.; Fuhrmann, G.; Bronner, C.; Schini-Kerth, V.B. Red
wine polyphenols cause growth inhibition and apoptosis in acute
lymphoblastic leukaemia cells by inducing a redoxsensitive up-
regulation of p73 and down-regulation of UHRF1. Eur. J. Cancer,
2010, 46, 983-994.
Mertens-Talcott, S.U.; Percival, S.S.; Talcott, S.T. Extracts from
red muscadine and cabernet sauvignon wines induce cell death in
MOLT-4 human leukemia cells. Food Chem., 2008, 108, 8516-
Dolara, P.; Luceri, C.; De Filippo, C.; Femia, A. P.; Giovannelli,
L.; Caderni, G.; Cecchini, C.; Silva, S.; Orpianesi, C.; Cresci, A.
Red wine polyphenols influence carcinogenesis, intestinal
microflora, oxidative damage and gene expression profiles of
colonic mucosa in F344 rats. Mutat. Res.-Fund. Mol. M., 2005,
Kim, M.-J.; Kim, Y.-J.; Park, H.-J.; Chung, J.-H.; Leem, K.-H.;
Kim, H.-K. Apoptotic effect of red wine polyphenols on human
colon cancer SNU-C4 cells. Food Chem. Toxicol., 2006, 44, 898-
Schneider, Y.; Vincent, F.; Duranton, B.; Badolo, L.; Gosseá, F.;
Bergmann, C.; Seiler, N.; Raul, F. Anti-proliferative effect of
resveratrol, a natural component of grapes and wine, on human
colonic cancer cells. Cancer Lett., 2000, 158, 58-91.
Eng, E.T.; Ye, J.J.; Williams, D.; Phung, S.; Moore, R. E.; Young,
M. K.; Ugis, G.; Braunstein, G.; Chen, S. Suppression of estrogen
biosynthesis by procyanidin dimers in red wine and grape seeds.
Cancer Res., 2003, 63, 8516-8522.
Bessaoud, F.; Daures, J. P. Patterns of alcohol (especially wine)
consumption and breast cancer risk: A case-control study among a
population in southern France, Ann. Epidemiol., 2008, 18, 467-475.
Gehm, B.D.; Levenson, A.S.; Liu, H.; Lee, E.-J.; Amundsen, B.M.;
Cushman, M.; Jordan, V.C.; Jameson, J. L. Estrogenic effects of
resveratrol in breast cancer cells expressing mutant and wild-type
estrogen receptors: role of AF-1 and AF-2. J. Steroid. Biochem.,
2004, 88, 223-234.
induced by wine
 Monteiro, R.; Faria, A.; Mateus, N.; Calhau, C.; Azevedo, I. Red
wine interferes with oestrogen signalling in rat hippocampus. J.
Steroid Biochem. Mol. Biol., 2008, 111, 74-79.
McDougall, G.J.; Shpiro, F.; Dobson, P.; Smith, P.; Blake, A.;
Stewart, D. Different polyphenolic components of soft fruits inhibit
?-amylase and ?-glucosidase. J. Agric. Food Chem., 2005, 53,
Gin, H.; Rigalleau, V.; Caubet, O.; Aubertin, J. Effects of red wine,
tannic acid, or ethanol on glucose tolerance in non-insulin
dependent diabetic patients and on starch digestibility in vitro.
Metabolism, 1999, 48, 1179-1183.
Montagut, G.; Bladé, C.; Blay, M.; Fernández-Larrea, J.; Pujadas,
G.; Salvadó, M.J.; Arola, L.; Pinent, M.; Ardévol, Effects of a
grapeseed procyanidin extract (GSPE) on insulin resistance. J.
Nutr. Biochem., 2010, 21, 961-967.
Yamakoshi, J.; Saito, M.; Kataoka, S.; Tokutake, S. Procyanidin-
rich extract from grape seeds prevents cataracta formation in
hereditary cataractous (ICR/f) rats. J. Agric. Food Chem., 2002, 50,
King, R.E.; Kenta, K.D.; Bomserb, J.A. Resveratrol reduces
oxidation and proliferation of human retinal pigment epithelial cells
via extracellular signal-regulated kinase inhibition. Chem.-Biol.
Interact., 2005, 151, 143-149.
Sheu, S.-J.; Wu, T.-T. Resveratrol protects against ultraviolet A-
mediated inhibition of the phagocytic function of human retinal
pigment epithelial cells via large-conductance calcium-activated
potassium channels. Kaohsiung J. Med. Sci., 2009, 25, 381-387.
Orgogozo, J.M.; Dartigues, J.F.; Lafont, S.; Letenneur, L.;
Commenges, D.; Salomon, R.; Renaud, S.; Breteler, M.B. Wine
consumption and dementia in the elderly: a prospective community
study in the Bordeaux area. Rev. Neurologia, 1997, 153, 185-192.
Truelsen T.; Thudium D.;, Gronbaek M. Amount and type of
alcohol and risk of dementia: the Copenhagen City Heart Study.
Neurology, 2002, 59, 1313–1319.
Luchsinger, J.A.; Tang, M.X.; Siddiqui, M.; Shea, S.; Mayeux, R.
Alcohol intake and risk of dementia. J. Am. Geriatr. Soc., 2004, 52,
Rodrigo, R.; Miranda, A.; Vergara, L. Modulation of endogenous
antioxidant system by wine polyphenols in human disease. Clin.
Chim. Acta, 2011, 412, 410–424.
Martin, S.; González-Burgos, E.; Carretero, M.E.; Gómez-
Serranillos, M.P. Neuroprotective properties of Spanish red wine
and its isolated polyphenols on astrocytes. Food Chem., 2011, 128,
Gao, Z.B.; Hu, G.-Y. Trans-resveratrol, a red wine ingredient,
inhibits voltage-activated potassium currents in rat hippocampal
neurons. Brain Res., 2005, 1056, 68-75.
Havsteen, B.H. The biochemistry and medical significance of the
flavonoids. Pharmacol. Therapeut., 2002, 96, 67-202.
Katalini?, V.; Smole Mo?ina, S.; Skroza, D.; Generali?, I.;
Abramovi?, H.; Milo?, M.; Ljubenkov, I.; Piskernik, S.; Pezo, I.;
Terpinc, P.; Boban, M. Polyphenolic profile, antioxidant properties
and antimicrobial activity of grape skin extracts of 14 Vitis vinifera
varieties grown in Dalmatia (Croatia). Food Chem., 2010, 119,
Papadopoulou, C.; Soulti, K.; Roussis, I.G. Potential antimicrobial
activity of red and white wine phenolic extracts against strains of
Staphylococcus aureus, Escherichia coli and Candida albicans.
Food Technol. Biotechnol., 2005, 43, 41-46.
Radovanovi?, A.; Radovanovi?, B.; Jovan?i?evi?, B. Free radical
scavenging and antibacterial activities of southern Serbian red
wines. Food Chem., 2009, 117, 326-331.
Király-Véghely, Z.; Móricz, A.M.; Ott, P.G.; Kátay, G.; Bélai, I.;
Tyihák, E. Comparison of components from red and white wines
for antimicrobial activity by biodetection after OPLC separation. J.
Liq. Chromatogr. Relat. Technol., 2009, 32, 1259-1272.
Ga?an, M.; Martínez-Rodríguez,
Antimicrobial activity of phenolic compounds of wine against
Campylobacter jejuni. Food Control, 2009, 20, 739-742.
Rodríguez Vaquero, M.J.; Alberto, M.R.; Manca de Nadra, M.C.
Infuence of phenolic compounds from wines on the growth of
Listeria monocytogenes. Food Control, 2007, 18, 587-593.
Daroch, F.; Hoeneisen, M.; González, C.L.; Kawaguchi, F.;
Salgado, F.; Solar, H.; García, A. In vitro antibacterial activity of
 A.J.; Carrascosa, A.V.
12 Mini-Reviews in Medicinal Chemistry, 2011, Vol. 11, No. 13 V. Rastija Download full-text
Chilean red wines against Helicobacter pylori. Microbios, 2001,
Just, J.R.; Daeschel, M.A. Antimicrobial effects of wine on
Escherichia coli O157 : H7 and Salmonella typhimurium in a
model stomach system. J. Food Sci., 2003, 68, 285-290.
Carneiro, A.; Couto, J.A.; Mena, C.; Queiroz, J.; Hogg, T. Activity
of wine against Campylobacter jejuni. Food Control, 2008, 19,
Daglia, M.; Stauder, M.; Papetti, A.; Signoretto, C.; Giusto, G.;
Canepari, P.; Pruzzo, C.; Gazzani, G. Isolation of red wine
components with anti-adhesion and anti-biofilm activity against
Streptococcus mutans. Food Chem., 2010, 119, 1182-1188.
Cleophas, T.J.: Wine, beer and spirits and the risk of myocardial
infarction: a systematic review. Biomed. @ Pharmacother. 1999,
Hvidtfeldt, U.A.; Tolstrup, J.S.; Jakobsen, M.U.; Heitmann, B.L.;
Grønbæk, M.; O'Reilly, E.; Bälter, K.; Goldbourt, U.; Hallmans,
G.; Knekt, P.; Liu, S.; Pereira, M.; Pietinen, P.; Spiegelman, D.;
Stevens, J.; Virtamo, J.; Willett, W.C.; Rimm, E.B.; Ascherio, A.:
Alcohol intake and risk of coronary heart disease in younger,
middle-aged, and older adults. Circulation, 2010, 121, 1589-1597.
Bleich, S.; Bleich, K.; Kropp, S.; Bittermann, H.-J.; Degner, D.;
Sperling, W.; Rüther, E.; Kornhuber, J.: Moderate alcohol
consumption in social drinkers raises plasma hamocysteine levels.
Alcohol & Alcoholism. 2001, 36, 189-192.
Ruidavets, J.-B.; Ducimetiére, P.; Evans, A.; Montaye, M.; Haas,
B.; Bingham, A.; Yarnell, J.; Amouyel, P.; Arveiler, D.; Kee, F.;
Bongard, V.; Ferriéres, J.: Patterns of alcohol consumption and
ischaemic heart disease in culturally divergent countries: the
Prospective Epidemiological Study of Myocardial Infarction
(PRIME). Brit. Med. J. 2010, 341, C6007.
Tolstrup, J.S.; Grønbæk, M.; Tybjærg-Hansen, A.; Nordestgaard,
B.G.: Alcohol intake, alcohol dehydrogenase genotypes, and liver
damage and disease in the Danish general population. Am. J.
Gastroenterol. 2009, 104, 2182-2188.
Cichoz-Lach, H.; Partycka, J.; Nesina, I.; Celinski, K.; Slomka, M.;
Wojcierowski, J.: Genetic polymorphism of alcohol dehydrogenase
3 in alcohol liver cirrhosis and in alcohol chronic pancreatitis.
Alcohol & Alcoholism. 2006, 41, 14-17.
Doberauer, C.; Henning, B.; Canner, B.: Early detection of
esophageal carcinoma in alcoholics by endoscopy with iodine
staining. Tumordiagnos. 1999, 20, 22-26.
Rod, N.H.; Hansen, Å.M.; Nielsen, J.; Schnohr, P.; Grønbæk, M.:
Low-risk factor profile, estrogen levels, and breast cancer risk
among postmenopausal women. Int. J. Cancer, 2009, 124, 1935-
Grønbæk, M.: The positive and negative health effects of alcohol-
and the public health implications. J. Intern. Med. 2009, 265, 407–
Strandberg-Larsen, K.; S?ndergaard Jensen, M.; Ramlau-Hansen,
C.H.; Gr?nb?k, M.; Olsen, J.: Alcohol binge drinking during
pregnancy and cryptorchidism. Hum. Reprod. 2009, 24, 3211-3219.
Goldberg, D. M.; Yan, J.; Soleas, G. J. Absorption of three wine-
related polyphenols in three different matrices by healthy subjects.
Clin. Biochem., 2003, 36, 79-87.
Manach, C.; Williamson, G.; Morand, C.; Scalbert, A.; Rémésy, C.
Bioavailability and bioefficacy of polyphenols in humans. I.
Review of 97 bioavailability studies. Am. J. Clin. Nutr., 2005, 81
Bertelli, A.A.E. Wine, research and cardiovascular disease:
Instructions for use. Atherosclerosis, 2007, 195, 242-247.
Pignatelli, P.; Ghiselli, A.; Buchetti, B.; Carnevale, R.; Natella, F.;
Germanò, G.; Fimognari, F.; Di Santo, S.; Lenti, L.; Violi, F.
Polyphenols synergistically inhibit oxidative stress in subjects
given red and white wine. Atherosclerosis, 2006, 188, 77-83.