C H A P T E R

5
Biological Activities of Polyphenols from Grapes
Enqin Xia*, Xiran He†, Huabin Li‡, Shan Wu‡, Sha Li‡ and Guifang Deng‡
*Department of Nutrition and Food Safety, School of Public Health, Guangdong Medical College, Dongguan, PR China
†
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, PR China ‡Guangdong
Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-
Sen University, Guangzhou, China

1. INTRODUCTION parts of grape and its products are displayed in

The grape (Vitis vinifera) constitutes one of the major
sources of phenolic compounds among different fruits,
which is widely considered as responsible for its
improvement effect on health. From the clue of the
“French paradox,” polyphenolics from grapes and red
wines have attracted the attention of scientists to
define their chemical composition and their properties
for human health.1 Studies have shown the positive
health effects of the grape and its products in the
improvement of some degenerative diseases.2,3 This
chapter mainly discusses the updated knowledge on
the bioactivities of grape polyphenols, as well as their
occurrence, bioavailability, and potential toxicity. It
emphasizes the health-promoting properties of pheno-
lic compounds in the grape and in the prevention of
various diseases. In addition, it also tries to show some
indications for further research direction and full utili-
zation of grape polyphenols.
2. THE DISTRIBUTION AND
OCCURRENCE OF DIFFERENT TYPES OF
PHENOLIC COMPOUNDS IN GRAPE
Table 5.1. It can be seen from Table 5.1, that there are
different phenolic compounds in different parts of the
grape and its products. In fact, the total concentration
of phenolic compounds is also different in several
sections of the plant.8 The skin mostly contains the
highest amount of condensed tannins, monomeric fla-
vanols and flavonols, phenolic acids and resveratrol.
The seeds are highest in phenol content (5
8% phenol
by weight). The rich presence of the low molecular
weight flavan-3-ols (such as catechins) and procyani-
din oligomers in seeds make them taste bitter. Usually,
the amount of total polyphenols in white grape
varieties is lower compared to that of red grapes due
to the absence of anthocyanins in white grapes.
Anthocyanins, red components, are responsible for the
color of red grapes.4,5 Compared to the grape tissues,
the concentration of phenolic compounds can reach 10-
to 20-fold the bioactive concentration in wine.
Degradation of cell-wall polysaccharides is a funda-
mental step to improve the release of phenols from
grape skin during its veraison procedure.9 Therefore,
phenolic compounds in wine contain almost all types
of grape phenols, which make it a good source of
grape phenolic compounds.

A large number of different phenolic compounds

are present in grape skin, pulp, seeds, leaf, as well as
in its product, wine.4,5 Some polyphenols from grapes
and its products have been identified, and the
chemical nature of the phenolic substances in grapes
has been amply studied. The chemical structures of
some phenolic compounds from grapes are illustrated
in Figure 5.1. The phenolic compounds in different
3. BIOACTIVITIES OF PHENOLIC
COMPOUNDS FROM GRAPE
Growing interest has focused on researching
the bioactivities of grape polyphenols, and the
positive effects on human health are summarized in
Figure 5.2.

Polyphenols in Human Health and Disease.

DOI: http://dx.doi.org/10.1016/B978-0-12-398456-2.00005-0 47 © 2014 Elsevier Inc. All rights reserved.
48 5. BIOLOGICAL ACTIVITIES OF POLYPHENOLS FROM GRAPES

OH HO TABLE 5.1 The Different Phenols in Several Parts of Grape and

OH Its Products
OH
HO O Resource Phenolic Compounds References
6,7
Seed Gallic acid, (1)-catechin, epicatechin,
OH epigallocatechin, dimeric procyanidin, or
OH
OH proanthocyanidins, tannins, quercetin-3-
Catechin Resveratrol glucuronide, catechin, caftaric acid, flavan-
3-ols, gallic acid and astilbin
OH 8,9
Skin Proanthocyanidins, ellagic acid, myricetin,
R3
quercetin, kaempferol, trans-resveratrol,
HO O tannins, anthocyanins, quercetin and
R4 kaempferol glucosides and glucuronides,
R2 gallic acid and its glucosides, caftaric and
coutaric acid
R1 O
9
Flavonols Pulp Phenolic acids and monomeric flavonoids,
R1 R2 R3 R4 flavanols
Quercetin OH OH OH - 8
Rutin OH O-Rutinose OH - Leaf Myricetin, ellagic acid, kaempferol,
Morin OH OH - OH quercetin, gallic acid
Myricetin OH OH OH OH 10
Fisetin OH OH OH - Stem Rutin, quercetin 3-O-glucuronide, trans-
resveratrol, astilbin
R1 Juice Hydroxycinnamoyl tartaric acids 7

R2
9
+ Red Malvidin-3-glucoside, peonidin-3-glucoside,
HO o wine cyanidin-3-glucoside, petunidin-3-glucoside,
R3
catechin, quercetin, resveratrol,
O-Gluc hydroxycinnamic acid
OH O
Anthocyanins
R1 R2 R3
Peonidin-3-O-glucoside OCH3 OH - power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH)
Petunidin-3-O-glucoside OH OH OCH3 radical scavenging activity, the oxygen radical absor-
Malvidin-3-O-glucoside OCH3 OH OCH3
Cyanidin-3-O-glucoside OH OH - bance capacity (ORAL) assay, the β-carotene bleaching
Delphinidin-3-O-glucoside OH OH OH (BCB), 2,20 -azobis(2-amidino propane)dihydrochloride
(AAPH), the antioxidative capacities (TEAC values).12
16
FIGURE 5.1 The chemical structures of some phenolic com- The results of antioxidant capacities of phenolic
pounds from grapes.
compounds extracted from various grapes, or different
parts of grapes, are illustrated in Table 5.2. As seen from
Table 5.2, the antioxidant capacities of extracts from
seeds were found to be higher than that from the skin,
3.1 Antioxidant and the flesh displayed the lowest antioxidant capacity.8
Grape phenols are powerful natural antioxidants. Grape phenols exert an antioxidant effect under dif-
They even have higher antioxidant activities than the ferent conditions with oxidative stress in vivo.
other well-known antioxidants, such as vitamin C.11 They can induce the reduction of intracellular reactive
Researchers have found that antioxidant activities were oxygen species (ROS) in different kinds of cells.21
23
significantly correlated with polyphenol content in both Grape juice decreases oxidative DNA damage induced
grape juice and wine.2,3 The antioxidative characteristics by H2O2 in peripheral blood cells.24 In addition, an
of phenolic compounds from grapes have been widely effective radiation (RTx)-induced oxidative stress can
studied in in vitro assays, including scavenging of free be inhibited by grape seed extract.25 What is more, the
radicals, inhibition of lipid oxidation, reduction of grape seed extract enhances the antioxidant resistance
hydroperoxide formation, and so on. Various methods against ROS produced under hyperglycemic condi-
have been employed to demonstrate the antioxidant tions.26,27 In terms of ultraviolet (UV)radiation, grape
capacities of phenolic compounds extracted from vari- seed polyphenols could be useful in the attenuation
ous grapes or different parts of grapes, such as the of oxidative stress as well.28
31 Also, red grape juice
superoxide scavenging activity (SOSA), thiobarbituric polyphenols reduce superoxide anion production.32
acid-reactive substances (TBARS or ABTS), ferrous iron Finally, grape pomace, with its high content of poly-
chelation activity (FICA), the ferric-reducing antioxidant phenols, shows prominent antioxidative capacity in

1. OVERVIEW OF POLYPHENOLS AND HEALTH

 3. BIOACTIVITIES OF PHENOLIC COMPOUNDS FROM GRAPE 49

Antioxidant Anti-inflammation

Cardiovascularprotection Anti-aging

Grape polyphenols
Neuroprotection Antimicrobe

Antitumor Other

FIGURE 5.2 The bioactivities of grape polyphenols.

properties.39,40 The mechanism was mainly speculated

TABLE 5.2 The Antioxidant Capacities of Grape Polyphenols to react directly to generate phenoxyl radicals,41 which
were stable and cut off the reaction chains. Therefore,
Resource TEAC FRAP DPPH ORAC References
the number of OH groups and their position on the
Grape 0.91 g/L
0.20 g/L
17
ring of the molecule determined the antioxidant capac-
pomace (EC50 ) (EC50 ) ity of flavonols.42 Di Majo et al.43,44 proved that when
Whole 76.3 mol 58.04 mol

18
OH was added onto the flavonoid nucleus, the activity
seed TE/100 g TE/100 g was enhanced, while substitution by OCH3 groups led
Grape 236.1 μmol


8 to diminished activity. The bearing o-diphenoxyl groups
leaf TE/g in resveratrol were proved to exhibit higher antioxidant
Grape 12.8 μmol



activity than other compositions.45
skin TE/g
Grape 2.4 μmol


3.2 Cardiovascular Protective
flesh TE/g
Experimental studies indicate that grape polyphe-
Grape 25 mmol 32 mmol 15 mmol
19

juice TE/L Fe21/L TE/L

Grape
3.098 mg 70.7% 10.724
wine TE/L inhibition μmol/L
TE, Trolox antioxidant equivalent.
inhibiting age-related or Cd-induced increase of lipid
peroxidation and DNA damage.33 Grape polyphenols
increase glutathione peroxidase, superoxide dismutase
and catalase activity, which play an important role in
suppressing oxidative stress.34
37 Recently, it was
reported that the grape seed extract tested, considered
as an antioxidant nutritive supplement, showed that
grape polyphenols are important sources of natural
antioxidants and may have pro-oxidant activity as well,
depending on the dose, duration of administration, and
other dietary components.38
In vivo assays showed that the antioxidative charac-
teristics of phenolic compounds are mainly attributed to
their free radical scavenging and metal chelating
nols could reduce atherosclerosis by inhibiting oxida-
tion of low-density lipoprotein (LDL) and exerting
20
other favorable effects on the cellular redox state,
improvement of endothelial function, lowering blood
pressure, inhibition of platelet aggregation, and reduc-
ing inflammation.46,47 The improvement of the cardio-
vascular system acts on the four steps during
development of atherosclerosis. Firstly, phenolic com-
pounds from grapes could prevent early atheroscle-
rotic events. The polyphenol resveratrol was the most
effective agent and prevented the disruption of aortic
elastic fibers, decreased their alteration, and reduced
the intima thickness and accumulation of fatty cells
and O22 in aortic tissues.48 Secondly, resveratrol mod-
erately downregulated the expression of the suppres-
sors of cytokine signaling 1 (SOCS1) and 3 (SOCS3),
the key regulators of vascular cell responses, in periph-
eral mononuclear blood cells.48 Thirdly, the red grape
skin polyphenolic extract (SGE) could inhibit vascular
endothelial growth factor (VEGF) and sphingosine-1-
phosphate (S1P)-mediated chemotaxis, which contrib-
ute to angiogenesis, by downregulating ERK and

1. OVERVIEW OF POLYPHENOLS AND HEALTH

50 5. BIOLOGICAL ACTIVITIES OF POLYPHENOLS FROM GRAPES
p38/MAPK phosphorylation and decreasing acute
platelet-activating factor synthesis.49 Furthermore,
polyphenols from grapes retarded the development of
aortic atherosclerosis in males as demonstrated by
significantly lower cholesterol content in the abdomi-
nal part.50 Polyphenols from fresh grape powder
directly affect macrophage atherogenicity by reducing
macrophage-mediated oxidation of LDL and cellular
uptake of oxidized LDL, which can eventually
reduce macrophage cholesterol accumulation and foam
cell formation and hence attenuate atherosclerosis
development.51
This effect of grape polyphenols consumption may
favor the reduction in cardiovascular risk. They may
play an important role as components of human diet in
prevention of cardiovascular or inflammatory diseases,
where blood platelets are involved, because they reduce
platelet adhesion, aggregation and generation of O22 in
blood platelets.52,53 It is reported that grape seed extract
prolongs clotting time and decreases the maximal veloc-
ity of fibrin polymerization in human plasma.54 Their
ability to inhibit platelet adhesion may be due to
restraining adhesion to fibrinogen and dose-dependent
inhibition of thrombin receptor activating peptide- and
ADP-induced platelet aggregation, and Ca21 mobiliza-
tion or activation platelet endothelial cell adhesion
molecule-1.55,56 Grape polyphenols were able to reduce
plasma concentrations of total cholesterol, LDL choles-
terol, triglyceride, free fatty acids, apolipoprotein B, and
increase those of high-density lipoprotein (HDL) chole-
sterol, which resulted in less accumulation of choles-
terol in the artery.57
66 The hypocholesterolemic activity
of grape seed polyphenols is most likely mediated by
enhancement of bile acid excretion, inhibition of pancre-
atic cholesterol esterase and upregulation of cholesterol-
7-α-hydroxylase (CYP7A1).60,67 Due to such beneficial
effects, grape seed extract alleviated all the deleterious
effects of a high fat diet treatment, such as heart hyper-
trophy, inflammation, cardiac steatosis and lipotoxi-
city.68 Shanmuganayagam et al.53 employed rabbits to
investigate the potential of phenolic compounds to
defend the hypercholesterolemic-induced platelet aggre-
gation. After intake of grape juice (225 mL/day), which
was rich in polyphenolics, with a hypercholesterolemic
diet for 96 days, platelet aggregation in rabbits was sig-
nificantly ameliorated and the developing atheroma
was nearly 30% lower than that of the control group.
Besides, grape polyphenols also reduced in vitro neutro-
phil NADPH oxidase activity and plasma concentra-
tions of oxidized LDL, which may be due to its
capability to trap reactive oxygen species in aqueous
series such as plasma and interstitial fluid of the arterial
wall.57,58,69
72 Finally, grape polyphenols could disrupt
or delay LDL trafficking in order to keep intracellular
lipid homeostasis, which increased both the expression
1. OVERVIEW OF POLYPHENOLS AND HEALTH
of the LDL receptor and the levels of the active form of
sterol regulatory element-binding protein-1.73
Grape seed proanthocyanidins have cardioprotec-
tive effects against ischemia/reperfusion-induced
injury by improving postischemic ventricular recovery
and reducing the amount of myocardial infarction.74,75
Phenolic compounds reduce the malonaldehyde con-
tent of the heart during ischemia and reperfusion due
to directly scavenging superoxide and hydroxyl radi-
cals.74,75 Red wine polyphenols significantly normalize
oxidative stress, the expression of SKCa, IKCa and the
components of the angiotensin system.76 Grape seed
extract also displays antihypertensive effect by signifi-
cantly lowering blood pressure and heart rate.53,61,77
81
Polyphenols from grapes can induce endothelium-
dependent relaxation, which may protect against
coronary artery disease. The polyphenols significantly
suppress inducible nitric oxide synthase (iNOS) gene
expression and NO production in the acellular system,
which directly damage the vascular walls during
atherosclerosis.82 Simultaneously, grape polyphenols
could induce vasorelaxation by NO formation in
the intracellular, which involve a nitric oxide (NO)-
mediated component, endothelial nitric oxide synthase
(eNOS).82
90 In addition, polyphenols-induced vasore-
laxation may also be sustained by smooth muscle
phosphodiesterases (PDEs) inhibition by anthocyanins
present in red wines and grapes.40 Grape polyphenols
may also contribute to the cardioprotective efficacy by
inhibiting cardiac voltage-gated sodium channels,
which are associated with arrhythmia.91 Finally, grape
polyphenols can ameliorate endothelial progenitor
cells viability and function, while preventing endothe-
lial dysfunction.22
Furthermore, research has shown that phenolic com-
pounds from grapes could protect against cardiac cell
apoptosis. Incubation of cardiac H9C2 cells with poly-
phenols resulted in a significant induction of cellular
antioxidant enzymes in a concentration-dependent fash-
ion.92 Furthermore, polyphenols pretreatment led to a
marked reduction in xanthine oxidase (XO)/xanthine-
induced intracellular ROS accumulation and cardiac cell
apoptosis.93
3.3 Anticancer
Many assays have demonstrated that extracts from
grapes and their products could be employed to fight
against carcinogenesis. The grape skin extract induced
prostate tumor cell lines apoptosis with high rates.86
The extract from pomace remains expressed a signifi-
cant antiproliferative effect on human colon adenocarci-
noma cells (Caco-2).94,95 Phenolics of grape juice also
significantly inhibited carcinogen-induced DNA adduct
 3. BIOACTIVITIES OF PHENOLIC COMPOUNDS FROM GRAPE
formation in the rat model,96 and inhibited DNA syn-
thesis in breast cancer cells.97 Resveratrol was found to
be anticarcinogenic in the whole development of can-
cers, including tumor incidence, tumor multiplicity and
tumor volume, respectively.98,99 Resveratrol was deter-
mined mainly bearing o-diphenoxyl groups, which dis-
played inhibiting DNA damage induced by ROS. The
anticancer effects of phenols from grapes and their
mechanism are summarized in Table 5.3.
Generally, the regulation target of grape extracts in
anticancer capacities involves downregulating various
genes linked to the tumor and enhanced proteosome deg-
radation; such as NF-κB, phospholipase C, calcium signal-
ing pathways, prostate-specific antigen, cell cycle
regulation, and inhibiting topoisomerase II,114 and inflam-
matory responses, as well as improving pro-oxidant activ-
ity leading to enhancement of DNA damage.93,115
3.4 Neuroprotective Agent
Research has showed that grape polyphenols or their
metabolites were able to cross the blood-brain barrier to
reach the brain, which suggested their potential value
for applications in neurodegenerative disorders.116
In vivo assays displayed the proteins associated with
Alzheimer’s disease (AD) or other neurodegenerative
disease in 13 rat brains that were altered in amount
51
and/or charged by grape seed extract.117 Grape seed
extract reduced the β-amyloid (Aβ), considered to be
responsible for the formation of senile plaques, and
which later accumulated in the brains of patients with
AD.118,119 Aβ fibril formation, amyloid plaques and
microgliosis in the brain of AD patients were also atten-
uated by grape polyphenols.119,120 Grape polyphenols
could polarize the immune response towards an anti-
inflammatory pathway, which suggests a valid thera-
peutic measure in mitigating neuro-inflammation in
Parkinson’s disease and AD.121
Moreover, grape polyphenols could modulate
τ-mediated neuropathologic mechanisms, supporting
the development of grape polyphenols for the preven-
tion and/or treatment of τ-associated neurodegenera-
tive disorders.122,123 Oral administration of grape seed
polyphenolic extract significantly attenuated the motor
skill decay as well as extended the lifespan in the R6/2
mice, a rodent model of Huntington’s disease, relative
to vehicle-control mice.124 Grape seed polyphenolic
extract treatment could inhibit polyQ aggregation in
the phaeochromocytoma (PC)-12 cell line containing
an ecdysone-inducible protein comprising the first 17
amino acids of Huntington plus 103 glutamines fused
with enhanced green fluorescent protein.124
In terms of temporomandibular joint disorders, grape
seed extract was found to suppress the development of
peripheral and central sensitization, through repressing

TABLE 5.3 The Anticancer of Phenols from Grapes and Its Mechanism
Grape Polyphenols Tumor/Tumor Cells Mechanism References
100
Piceatannol T24 and HT1376 human Block cell cycle progression in the G0/G1 phase, induce apoptosis
bladder cancer cells
101,102
Resveratrol, SK-Mel-28 melanoma cells Induce growth inhibition, apoptosis, S-phase arrest, upregulate cyclins
piceatannol A, E, B1
103
105
Resveratrol, grape CaCo-2 cells Decrease ornithine decarboxylase and phenol sulfotransferases activity,
polyphenols induce DNA fragmentation
106
Grape polyphenols C26 colon carcinoma Blunt tumor vascularization, induce apoptosis
107
Grape seed extract MDA-MB-231 breast cancer Inhibit VEGF-induced endothelial cell proliferation and migration
cells
108
Anthocyanin HepG2 liver cancer cell DNA fragmentation
109
Resveratrol UVB-mediated skin tumors Reduce in Survivin, thus inducing apoptosis
110
Grape polyphenols Mammary tumor Upregulation of forkhead box O1 and IκBα, thus activating apoptosis
111
Red grape wine MCF-7 breast cancer cells Disrupt mitochondrial function and cause membrane damage
polyphenol
112
Piceatannol Prostate cancer cells Increased the levels of cleaved caspase-8, -9 and mitochondrial
membrane permeability
113
Piceatannol AH109A hepatoma cells Scavenge intracellular ROS and induce apoptosis

1. OVERVIEW OF POLYPHENOLS AND HEALTH

52 5. BIOLOGICAL ACTIVITIES OF POLYPHENOLS FROM GRAPES
phosphorylated-p38, OX-42, and glial fibrillary acidic
protein neuropeptide calcitonin gene-related peptide.125
Grape seed extract acting on astrocytes increased
interleukin-6 (IL-6) production, which functions as a
neuroprotective paracrine, and could protect neuronal
cells from death by oxidative stress.126
3.5 Anti-Inflammation
Grape polyphenols have a potential health effect on
inflammatory conditions. Resveratrol was found to
be able to enhance intraphagocytosis in human
promonocytes and reduce parenchymal inflammation in
ischemia/reperfusion in rat kidneys.127,128 Furthermore,
grape polyphenols exerted a protective effect on
recurrent colitis by inhibiting inflammatory cell infil-
tration and antioxidation damage, promoting dam-
aged tissue repair to improve colonic oxidative
stress, and inhibiting colonic iNOS activity to reduce
the production of NO.129 The antioxidative properties
of grape polyphenols attenuate inflammatory changes
induced by the coculture of adipocytes and macro-
phages.130 In a model of ear inflammation, extracts of
grape seed treatments significantly reduced ear
edema and ear biopsy weight.131
Importantly, grape polyphenols are able to inhibit
the production of inflammatory cytokines. The mecha-
nism involved in reducing myeloperoxidase (MPO)
activity and decreasing the production of inflamma-
tory mediators such as NO, NF-κB, prostaglandin (PG)
E2, prostaglandin (PG)D2, COX-2.132
136 The produc-
tion of pro-inflammatory cytokines such as C-Reactive
Protein (CRP), TNF-α, IL-1β and IL-6 can be attenuated
by polyphenols.137,138 The polyphenols from grapes
can enhance the production of the anti-inflammatory
cytokine adiponectin.138
3.6 Antimicrobial
Grape polyphenols have been used as a natural
antimicrobial agent. Researchers have demonstrated
that grape extracts inhibited the growth of
Staphylococcus aureus, including methicillin-resistant
Staphylococcus aureus strains, Helicobacter pylori
(H. pylori), Alicyclobacillus acidoterrestris,
Streptococcus mutans.139
146 In terms of Bacillus cereus,
Escherichia coli O157:H7, Salmonella infantis,
Campylobacter coli and Listeria monocytogenes, grape
polyphenols also exhibited antibacterial proper-
ties.147,148 Grape seed extract also had a bacteriostatic
effect on the anaerobes, which indicates that grape
seed extract could be used in oral hygiene for the pre-
vention of periodontitis.149 The inhibitory effect of
phenolic compounds from seed extracts is more
1. OVERVIEW OF POLYPHENOLS AND HEALTH
potent against Gram-positive than Gram-negative bac-
teria.150 Antibacterial activity of grape polyphenols
becomes bactericidal by a disruption of the bacterial
cell wall and folate-mediated one-carbon metabo-
lism.144,151,152 In terms of H. pylori, grape polyphenol
was able to inhibit VacA to prevent gastric epithelium
damage.145 Researchers have demonstrated that grape
polyphenols are effective against Candida albicans as
well.153,154
3.7 Anti-Aging
Studies showed that grape juice could enhance neu-
rocognitive function in older adults with mild memory
decline, because polyphenols (including anthocyanins
and flavanols) reduce semantic interference on mem-
ory tasks and improved verbal learning capabil-
ity.155,156 Relatively greater activation in anterior and
posterior regions of the right hemisphere was also
observed after consuming grape juice containing high-
er polyphenols.155 In addition, animal studies have
found that after an intake of grape seed extract in aged
rats, the memory retention could improve in a water
maze performance.157 Besides, phenolic phytochem-
icals extracted from grapes could scavenge carbonyl
and inhibit protein glycation, which could be beneficial
in preventing age-related chronic diseases.158
3.8 Other Activities
Polyphenols displayed some positive effects during
brain ischemia. Polyphenols alleviated the acute inacti-
vation of ERK1/2 and dendrite retraction in cultured
hippocampal neurons exposed to a toxic concentration
of glutamate, of which excitotoxicity is one of the
major events that takes place during brain ischemia.159
In addition, dietary grape polyphenol was able to pro-
tect neurons against ischemia/reperfusion (I/R)-
induced delayed neuronal death, DNA damage, and
apoptosis as well as attenuated glial cell activa-
tion.160,161 In addition, grape polyphenols may have
some benefit in altering the progression of diabetic
complications, anti-obesity, anti-HIV, improvement of
gastrointestinal health, and so on.162
166
and
4. BIOAVAILABILITY
Researchers have showed that procyanidins, quercetin
and flavanols from grapes could be absorbed into plasma
2 or 3 hours after ingestion.167 In other assays, after 2
weeks of daily red wine consumption (375 mL), plasma
levels of total phenolic concentrations increased signifi-
cantly, compared to the control groups. Moreover, the
 REFERENCES
trace levels of metabolites, mainly glucuronides and
methyl glucuronides of (1)-catechin and (2)-epicate-
chin, were detected in plasma.168 Employed as in vitro
digestion/Caco-2 cell culture model, Laurent et al.169
found that the availability of phenolic compounds was
not affected by salivary and gastric incubations but
decreased during intestinal digestion. These results indi-
cate that phenolic compounds could be absorbed by the
human digestion system, and enter into blood success-
fully. However, the mechanism of polyphenols entering
plasma is still unclear.
5. POTENTIAL TOXICITY
Several toxicity experiments have shown that
grape polyphenols are lowly toxic or non-toxic.
Studies on the polyphenolic fractions showed high
antioxidant capacity in a concentration range that
was not harmful to normal human cells.170,171 A toxic-
ity study found that a dietary concentration of 2.5%
grape seed extract or 2.5% grape skin extract was con-
sidered to be a no observed adverse effect level.172
Administration of the grape seed extract IH636 to
male and female Sprague-Dawley rats was conducted
at levels of 0.5, 1.0, or 2.0% for 90 days. The results
showed that grape seed extracts did not induce any
significant toxicological effects.173 The lethal dose of
50 grape polyphenols was higher than 5000 g/kg.174
In addition, the bacterial reverse mutation test
showed that the extracts were weakly mutagenic to
the dose of 5 mg/plate, and 19.5 and 9.7 μg/mL of
grape seeds and skins extract did not show signifi-
cant differences in the frequency of aberrant meta-
phases in relation to negative controls.174
6. CONCLUSION
Grape polyphenols as natural oxidants have proven
to be a dietary supplement that could express various
favorable effects on human health, including potential
agents to treat various kinds of chronic and degrada-
tive diseases. Grape wine could be considered as a
favorable source of grape phenolic compounds com-
pared to seeds and skins of grapes due to it containing
higher levels of potentially bioactive polyphenols.
Therefore, an economical and efficient extraction
method ought to be developed to make the best use of
the main sources of polyphenols in the seeds and skins
of grape. In addition, more research should be carried
out to study the bioavailability of grape polyphenols,
which determines whether they can be utilized widely
or not.
1. OVERVIEW OF POLYPHENOLS AND HEALTH
53
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