Resveratrol - cancer, a xxi century approach

footlickertreeBiotechnology

Dec 3, 2012 (4 years and 8 months ago)

561 views

RESVERATROL

BELZUZARRI 2

.
-


90 CAPSULES with 500 MG of RESVERASTROL. , 40 Euros.

Dose.
-

Two capsules daily.

You can order
BELZUZARRI 2
by email to
alfredobelzuzarri@gmail.com

a
nd we will send them
to
your ho
me by SEUR

(in Spain)
.
You will pay them when you recieve them.


What they say about Resveratrol



Resveratrol a "very hot topic
."



Rhoda Cobin, MD, a clinical professor of medicine at Mount Sinai Medical Center in
New York



"
People think this may be
t
he

elixir
,'‘



Dr. Cobin, a past president of the American Association of Clinical Endocrinologists.



"
This is a potential medication that could be used in multiple areas
,"



Kimberly Martin, MD, a pediatric endocrinology fellow at Case Western Reserve
University in Cleveland, Ohio.



Mimics caloric restriction

.
-
“Caloric restriction has a powerful, protective effect
against diseases associated with aging. We don’t know how long

each individual will
end up living, but they certainly have a longer life expectancy than average.” Mason
M. ,
New York Times
, October 31, 2006. Available at:
http://www.nytimes.com
.



Fit and healthy
.
-

Those given
a high
-
calorie diet plus resveratrol steadily improved
their motor skills as they aged, to the point where they were indistinguishable from
the standard
-
diet group.
Dr Rafael de Cabo (National Institute on Aging) heart
wire




“This is important, as it
suggests that this compound may not just extend life but may
also enable individuals to lead healthy and functional lives for longer," Dr Rafael de
Cabo (National Institute on Aging) heart
wire



neurodegenerative disease
.
-

“In mice, calorie restriction doe
sn’t just extend life span,
it mitigates many diseases of aging: cancer, cardiovascular disease, neurodegenerative
disease. The gain is just enormous.” Dr Leonard P Guarente (Massachusetts Institute of
Technology, Cambridge



Cardiovascular effects
.
-

In term
s of cardiovascular effects, the researchers found that
mice given resveratrol along with a high
-
fat diet had less damage to cardiac muscle
and healthier aortic tissue than those given a high
-
fat diet without resveratrol. Drs
Joseph Baur (Harvard Medical S
chool, Boston, MA) and Kevin Pearson (National
Institute on Aging, Baltimore, MD). published online in
Nature

on November 1, 2006



Improved

glucose tolerance
.
-

Resveratrol improved glucose tolerance and prevented
the detrimental effects of the high
-
calorie
diet on the liver.
“I was not a believer until I
did the autopsies in the mice and I saw the pathologies of the liver. I was blinded to
which group was which, but there were clear differences between those on resveratrol
and those not. I was floored by so
me of these effects." De Cabo heart
wire




Resveratrol improves glycemia by stimulating glucose transport in certain tissues,
including the skeletal muscle that expresses the insulin
-
sensitive GLUT4 isoform of
glucose transporters.



AIDS too.
-

Resveratrol
. A novel inhibitor of ribonucleotide reductase.



Resveratrol potentiates the anti
-
HIV activity of nucleoside analogues such as ddI, ddC,
and ZDV.



The mechanism of action is believed to be similar to that of hydroxyurea, but
Resveratrol has less of an antip
roliferative effect than hydroxyurea.



Resveratrol plus ddI resulted in a 200
-
fold increase in anti
-
HIV activity in vitro
(resveratrol has no intrinsic antiviral activity).



Resveratrol plus ddI also resulted in marked inhibition of 2 ddI
-
resistant viral
isolates.



Davis C, Heredia A, Redfield R. The synergistic inhibition of HIV
-
1 with nucleoside
analogs combined with a natural product, resveratrol. Program and abstracts of the
7th Conference on Retroviruses and Opportunistic Infections; January
30
-
February 2,
2000; San Francisco, Calif. Abstract 509. on of 2 ddI
-
resistant viral isolates.



Anticancer effects too.
-

Resveratrol is also being studied as an anticancer agent, with
potent anticancer activity having been shown in vitro and in animal stud
ies. “Its
anticancer action may be related to its antiaging effects, but it has many other actions
as well that may be more relevant to the antiaging observations," Dr Rafael de Cabo
(National Institute on Aging) heart
wire



Resveratrol blocked the formatio
n of preneoplastic lesions, suppressed mammary
carcinogenesis, reduced tumor incidence, and increased tumor latency in Sprague
-
Dawley rats treated with dimethylbenz[
a
]anthracene (DMBA). (Whitsett et al. 2006).



Resveratrol bind both ER
-
α
and ER
-
ß and to

induce the transcription of estrogen
-
responsive target genes in a dose
-
dependent manner.
(Bowers et al. 2000; Kuiper et
al. 1997, 1998; Maggiolini et al. 2001).

Resveratrol

From Wikipedia, the free encyclopedia

Resveratrol




Chemical structures
of

cis
-

((Z)
-
resveratrol, left) and

trans
-
resveratrol ((E)
-
resveratrol, right)
[1]

Other names
[hide]

trans
-
3,5,4'
-
Trihydroxystilbene;

3,4',5
-
Stilbenetriol;

trans
-
Resveratrol;

(
E
)
-
5
-
(
p
-
Hydroxystyryl)resorcinol;

(
E
)
-
5
-
(4
-
hydroxystyryl)benzene
-
1,3
-
diol

Identifiers

CAS
number

501
-
36
-
0


PubChem

445154

ChemSpider

392875


UNII

Q369O8926L


DrugBank

DB02709

KEGG

C03582


ChEBI

CHEBI:45713


ChEMBL

CHEMBL165


RTECS number

CZ8987000

Jmol
-
3D images

Image 1

SMILES

[show]

InChI

[show]

Properties

Molecular formula

C
14
H
12
O
3

Molar mass

228.24 g mol

1

Appearance

white powder with

slight yellow cast

Melting point

261
-

263°C /
501.8
-

505.4°F
[2]

Solubility

in
water

0.03 g/L

Solubility

in
DMSO

16 g/L

Solubility

in
ethanol

50 g/L

λ
max

304nm (trans
-
resveratrol, in water)

286nm (cis
-
resveratrol,
in water)
[1]

Hazards

MSDS

Fisher Scientific
[2]

Sigma Aldrich
[3]

R
-
phrases

R36

(irritating to eyes)
[3]

S
-
phrases

S26

(in case

of contact with eyes, rinse immediately
with plenty of water and

seek medical advice)
[3]

LD
50

23.2 µM (5,29 g)
[4]


Except where noted otherwise, data are given for materials in
their

standard state (at 25

°C, 100

kPa)

Resveratrol

(3,5,4'
-
trihydroxy
-
trans
-
stilbene) is a

stilbenoid
, a type of

natural phenol
, and
a

phytoalexin

produced naturally by several plants when under attack by

pathogens

such
as

bacteria

or

fungi
.

The effects of resveratrol
are currently a topic of numerous animal and human studies. Its effects on
the lifespan of many model organisms remain controversial, with uncertain effects in fruit flies,
nematode worms,
[5]

and short
-
lived fish. In mouse and rat experiments, anticancer,

anti
-
inflammatory
, blood sugar
-
lowering and other beneficial
cardiovascular

effects of resveratrol have
been reported. In humans, however, while reported effects are generally positive, resveratrol may
have lesser benefits.
[6]

In one positive human trial, extremely high doses (3

5

g) of resveratrol, in a
proprietary formulation designed to enhance its

bioavailability
, significantly lowered

blood
sugar
.
[7]
This 28
-
day Phase 1b study was conducted privately in

India

by the pharmaceutical
company,

Si
rtris
, and was announced at an investor conference in 2008.
[8]

Although it has been
alluded to in review articles, the study has never been published in a peer
-
rev
iewed scientific
publication. Despite the mainstream press alleging resveratrol's anti
-
aging effects,
[9]

there are no
accepted data to form a scientific basis for the application of
these claims to mammals (see

life
extension

section below). At the present time, research on resveratrol is in its infancy and the long
-
term effects of supplementation in human
s are not known.
[10]
[11]

Resveratrol is found in the skin of red grapes and in other fruits. Red wine contains very little of it,
however, on the order of 0.1
-
14.3

mg/l.
[12]

Res
veratrol also has been produced by chemical
synthesis

[13]

and by biotechnological synthesis (metabolic engineered microorganisms),
[14]
[15]

and it is
sold as a

nutritional supplement

derived primarily from
Japanese knotweed
.
[
citation needed
]

Contents



1

Discovery and name



2

Recent studies

o

2.1

Life extension

o

2.2

Cancer prevention

o

2.3

Cardioprotective effects

o

2.4

Antidiabetic effects

o

2.5

Other a
pplications

o

2.6

Applications that have been demonstrated ineffective



3

Pharmacokinetics

o

3.1

Adverse effects and unknowns



3.1.1

Possible carcinogenicity



4

Mechanisms of action



5

Chemical and physical properties



6

Metabolism

o

6.1

Biosynthesis

o

6.2

Biotransformation



7

Occurrences

o

7.1

In pla
nts

o

7.2

In foods



7.2.1

Content in wines and grape juice



7.2.2

Content in selected foods

o

7.3

Supplementation



8

Related compounds



9

See also



10

References



11

External links

Discovery and name

The first mention of resveratrol was in a

Japanese

article in 1939 by Michio Takaoka, who isolated it
from the poisonous, but medicinal,

veratrum album
, variety

grandiflorum
.
[16]
The name presumably
comes from the fact that it is a

resorcinol

derivative coming from a
veratrum

species.
[17]

[
edit
]
Recent studies

Life extension

The groups of Howitz and Sinclair reported in 2003 in the journal,

Nature
, that resveratrol significantly
extends the lifespan of the

yeast

Saccharomyces cerevisiae
.
[18]

Later studies conducted by Sinclair
showed

that resveratrol also prolongs the lifespan of the worm,

Caenorhabditis elegans
, and the fruit
fly,

Drosophila melanogaster
.
[19]

In 2007, a different group of researchers were able to reproduce
Sinclair's results with

C. elegans
,
[20]
but a third group could not achieve consistent increases in
lifespan of either

D. melanogaster

or

C. elegans
.
[5]

In 2006,

Italian

scientists obtained the first positive result of resveratrol
supplementation in
a

vertebrate
. Using a short
-
lived fish,
Nothobranchius furzeri
, with a median life span of nine weeks.
They found a maximal dose of resveratrol increased the median lifespan by 56%. Compared with the
control fish at nine weeks, that is, by the end of control fish's life, the fish supplemented with
resveratrol showed
significantly higher swimming activity and better learning to avoid an unpleasant
stimulus. The authors noted a slight increase of mortality in young fish caused by resveratrol, and
hypothesized that its weak toxic action stimulated the defense mechanisms
and resulted in the life
span extension.
[21]

Later the same year, Sinclair reported resveratrol counteracted the detrimental effects of a high
-
fat
diet in mice. The hi
gh
-
fat diet was compounded by adding hydrogenated

coconut oil

to the standard
diet; it provided 60% of energy from fat, and the mice on it consumed about 30% more calories than
the m
ice on standard diet and became obese and diabetic. Mice on the high
-
fat diet exhibited a high
mortality rate compared to mice fed the standard diet; mice fed the high
-
fat diet plus 22

mg/kg
resveratrol had a 30% lower risk of death than the mice on the hi
gh
-
fat diet alone, making their death
rates similar to those on the standard diet. The supplement also partially corrected a subset of the
abnormal

gene expression

profile an
d abnormal

insulin

and

glucose

metabolism. Resveratrol
supplements did not change the levels of free fatty acids and
cholesterol, however, which were much
higher than in the mice on standard diet.
[22]

A further study by a group of scientists, which included Sinclair, indicated resveratrol

treatment had a
range of beneficial effects in elderly mice, but did not increase the longevity of

ad libitum

fed (freely
-
feeding) mice when started midlife.
[23]

Later, the

National Institute on Aging
's Interventions Testing
Program (ITP)

[24]

also tested three different doses of resveratrol in mice on a normal diet beginning
in young adulthood, and again found no effect on lifespan, even at doses roughly eight

times higher
than those that had normalized the lifespan of the high
-
fat
-
fed, obese mice in the earlier study.
[25]

2011 study published in

Nature

suggested that some of
the benefits demonstrated in previous
studies were overrepresented,
[26]
[27]
however, this study was challen
ged immediately,
[28]

and few
experiments were suggested to be of inferior quality.
[29]

Johan Auwerx (at the Institute of Genetics and Molecular and Cell Biology in Illkirch,

France
) and
coauthors published an online article in the journal

Cell

in November 2006. Mice fed resveratrol for
fifteen weeks had better treadmill endurance than controls. The study supported Sinclair's hypothesis
that the effects of resveratrol are indeed due to the

activation

of the

Sirtuin 1

gene.
[
citation needed
]

Nicholas Wade's interview
-
article with Dr. Auwerx
[30]

stated the dose was
400

mg/kg of body weight
(much higher than the 22

mg/kg of the Sinclair study). For an 80

kg (175

lb) person, the 400

mg/kg of
body weight amount used in Auwerx's mouse study would total 30,000

mg/day. Compensating for
the fact that humans have slower meta
bolic rates than mice would change the equivalent human
dose to roughly 4000

mg/day. Again, there is no published evidence anywhere in the scientific
literature of any clinical trial for efficacy in humans. There are limited human safety data. Long
-
term
sa
fety has not been evaluated in humans.
[
citation needed
]

In a study of 123

Finnish

adults, those born with certain increased variations of the SIRT1 gene had
faster metabolisms, helping them to burn more energy, indicating the same pathway shown in the
laboratory mice works in humans.
[31]

Cancer prevention

In 1997, Jang reported that topical resveratrol applications prevented skin cancer development in
mice treated with a

carcinogen
.
[32]
There have since been many studies of the anti
-
cancer activity of
resveratrol in animal models.
[12]

Resveratrol has been shown to induce

apoptosis

in platelets,
[33]
[34]

and smooth muscle.
[35]
[35]
[36]

No results of human clinical trials for cancer have been reported.
[37]

Clinical trials to investigate the effects on

colon cancer

and

melanoma

(skin cancer) are currently
recruiting patients.
[38]

The study of pharmacokinetics of resveratrol in humans concluded,
however,
that even high doses of resveratrol might be insufficient to achieve the resveratrol concentrations
required for the systemic prevention of cancer.
[39]

This is

consistent with the results from the animal cancer models, which indicate the

in
vivo

effectiveness of resveratrol is limited by its poor systemic bioavailability.
[40]
[41]

The strongest
evidence of anticancer action of resveratrol exists for tumors it can contact direc
tly, such as skin
and

gastrointestinal tract

tumors. For other cancers, the evidence is uncertain, even if massive doses
of resveratrol are used.
[37]

Thus, resveratrol (1

mg/kg orally) reduced the number and size of the

esophageal tumors

in
rats
treated with a carcinogen;
[42]

and in several studies, small doses (0.02

8

mg/kg) of resveratrol,
given

prophylactically
, reduced or prevented the development of intestinal and colon tumors in rats
given different carcinogens.
[37]

Similarly,

topical application

of resveratrol in mice, both before and
after the
UVB

exposure, inhibited the skin damage and decrease
d skin cancer incidence, however,
oral resveratrol was ineffective in treating mice

inoculated

with melanoma cells. Resveratrol given
orally also had no effect on

leukemia

and lung cancer;
[37]
[43]

however, injected
intraperitoneally
, 2.5 or
10

mg/kg of resveratrol slowed the growth of metastatic

Lewis lung carcinomas

in mice.
[37]
[44]

Resveratrol treatment appeared to prevent the development of mammary tumors in animal models;
however, it had no effect on the growth of existing tumors. Paradoxically, treatment of prepubertal
mice with hig
h doses of resveratrol enhanced formation of tumors. Injected in high doses into mice,
resveratrol slowed the growth of

neuroblastomas
.
[37]

All of the aforementioned

in vivo

studies have been in animal models in which the cancer has been
artificially induced by some experimental means. Three other studies have investigated the effect of
resvera
trol on the risk of cancer in normal mice living out a normal lifespan; all of them have found
resveratrol supplementation has no significant effect on the burden of tumors, nor on the rate of
cancer death.
[23]
[25]
[45]

Cardioprotective effects

Moderate
drinking of red wine has long been known to reduce the risk of heart disease.
[46]

This is
best known as “the

French paradox
”.
[47]
[48]
[49]

Studies suggest resveratrol in red wine may play an important role in this phenomenon.
[50]

It achieves
the effec
ts by the following functions: (1) inhibition of vascular cell adhesion molecule
expression;
[51]
[52]

(2) inhibition of vascular smooth muscle cell proliferation;
[53]
[54]
[55]

(3) stimulation of
endolethelial nitric oxide synthase (eNOS) activity;
[56]
[57]
[58]

(4) inhibition of platelet
aggregation;
[59]
[60]
[61]
[62]

and (5) inhibition of LDL peroxidation.
[63]
[64]

The cardioprotective effects of resveratrol also are theorized to be a form of preconditioning

the
best method of cardioprotection, rather than

direct therapy.
[65]

Study into the cardioprotective effects
of resveratrol is based on the research of

Dipak K. Das
, however, who has been found guilty of
scientific fraud and many of his publications related to resveratrol have been retracted.
[66]
[67]

A 2011
study concludes, “Our data demonstrate that both melatonin and resveratrol, as found in red wine,
protect the heart in an experimental model of myocardial infarction via the

SAFE

pathway.”
[68]

Antidiabetic effects

Studies have shown resveratrol possesses

hypoglycemic

and

hypolipidemic

effects in
both

streptozotocin

(STZ)
-
induced diabetes rats and STZ
-
nicotinamide
-
induced diabetes rats.
Resveratrol ameliorates common diabetes symptoms, such as

polyphagia
,

polydipsia
, and body
weight loss.
[69]

Other diabetic anim
al model studies by different researchers have also demonstrated
the antidiabetic effects of resveratrol.
[22]
[31]
[70]
[71]
[72]
[73]
[74]

In human clinical trials, resveratrol has lowered

blood sugar levels

in both Phase Ib and Phase IIa
research, conducted by Sirtris Pharmaceuticals, I
nc.
[75]
[76]

Other applications

Neuroprotective effects

In November 2008, researchers at the

Weill Medical College

of

Cornell University

reported dietary
supplementation

with resveratrol significantly reduced plaque formation in animal brains, a critical
part of the pathogenesis of

Alzheimer's disease

and other neurodegenerative di
seases.
[77]

In mice,
oral resveratrol produced large reductions in CNS plaque formation in the hypothalamus (−90%),
striatum (−89%), and medial cortex (−48%) sections o
f the brain. In humans, oral doses of
resveratrol theoretically may reduce beta amyloid plaque associated with aging changes in the brain.
Researchers theorize that one mechanism for plaque eradication is the ability of resveratrol to
chelate (bind) copper
. The neuroprotective effects have been confirmed in several animal model
studies.
[78]
[79]
[80]
[81]
[82]

These effects may be in part caused by its

RIMA

effects.

Anti
-
inflammatory effects

The anti
-
inflammatory
effects of resveratrol have been demonstrated in several animal model
studies. In a rat model of

carrageenan
-
induced paw

edema
, resveratrol inhibited both acute and
chronic phases of the inflammatory process.
[83]

Similarly, preincubation with resveratrol decreased
arachidonic acid releas
e and COX
-
2 induction in mouse peritoneal macrophages stimulated with
tumor promoter PMA, ROI, or lipopolysaccharides (LPS).
[84]

In an experimental rabbit inflammatory
arthritis model, resveratrol showed promise as a potential therapy for arthritis. When administered to
rabbits with induced inflammatory arthritis, resveratrol protected cartilage against the progression of
inflammatory arthritis.
[85]

Antiviral effects

Studies show resveratrol inhibits

herpes simplex virus

(HSV) types 1 and 2 repl
ication by inhibition of
an early step in the virus replication cycle.

In vivo

studies in mice found resveratrol inhibits or reduces
HSV replication in the vagina and limits extravaginal disease. The skin of resveratrol
-
treated animals
showed no apparent
dermal toxicity, such as

erythema
, scaling, crusting,
lichenification
,
or

excoriation
.
[86]
[87]
[88]

Studies also show resveratrol inhibits

varicella
-
zoster virus
, certain

influenza
viruses
, respiratory viruses, and

human cytomegalovirus
. Furthermore, re
sveratrol synergistically
enhances the anti
-
HIV
-
1 activity of several anti
-
HIV drugs.
[89]
[90]
[91]
[92]
[93]
[94]

Effect on testosterone levels

A

Korean

study showed that

trans
-
resveratrol supplementation increased testosterone levels in
mice

in vivo
,
[95]

which has led to its marketing as a bodybuilding supplement. A

Spanish

study has
also shown the antioxidant to increase sperm production in rats.
[96]

Selective and Reversible

MAO
-
A

inhibiting effects (
RIMA
)

Resveratrol
has been found to be a potent and highly selective reversible inhibitor of monoamine
oxidase type A (RIMA) with an IC
50

of 2.0μM and a K
i

value of 2.5μM in rat brains. This effect is
expected to be related to its potent antioxidant activity.

[97]

[
edit
]
Applicat
ions that have been demonstrated ineffective

Antimicrobial effect

Resveratrol has been shown to be ineffective in inhibiting the growth of the yeast

Candida
albicans

and
other

Candida

species.
[98]

Pharmacokinetics

One way of administering resveratrol in humans may be

buccal

delivery, that is without swallowing,
by direct absorption through tissues on the inside of the mouth. When one milligram of resveratrol in
50 ml 50% alcohol/ water solut
ion was retained in the mouth for one minute before swallowing,
37

ng/ml of free resveratrol were measured in plasma two minutes later. This level of unchanged
resveratrol in blood can only be achieved with 250

mg of resveratrol taken in a pill form.
[99]

However,
the viability of a buccal delivery method is called into question due to the low aqueous solubility of the
molecule. For a drug to be absorbed via the transmuco
sal membrane, the drug must be in free
-
form
or dissolved.
[100]
[101]

Resveratrol

fits the criteria for oral transmucosal dosing, except for this caveat.
The low aqueous solubility greatly limits the amount that can be absorbed through the buccal
mucosal, and is why the method has not been seriously explored further. All resveratrol th
at is
attempted to be taken buccaly will fail to pass through the mucous membrane of the mouth and be
absorbed as an oral dose,
[102]

however, a need to explore buccal
delivery in future pharmaceutical
formulations has been expressed.
[101]
[103]

A
bout 70% of the resveratrol dose given orally as a pill is absorbed; nevertheless, oral bioavailability
of resveratrol is low because it is rapidly metabolized in intestines and liver
into

conjugated

forms:

glucuronate

and

sulfonate
.
[104]

Only trace amounts (below 5

ng/ml) of
unchanged resveratrol could be detected in the blood after 25

mg oral dose.
[104]

Even when a very
large

dose (2.5 and 5 g) was given as an uncoated pill, the concentration of resveratrol in blood failed
to reach the level claimed to be necessary for the systemic cancer prevention.
[39]

A formulation of
resveratrol in a chewing gum form is now in production, and this would be expected to achieve much
higher blood levels than oral formulations. Resveratrol given in a proprietary formulation SRT
-
501 (3
or 5 g), developed by S
irtris Pharmaceuticals, reached five to eight times higher blood levels. These
levels did approach the concentration necessary to exert the effects shown in animal models and

in
vitro

experiments.
[7]

On May 5, 2010, however,

GlaxoSmithKline

(GSK) said it had suspended a
small clinical

trial of SRT501, a proprietary form of resveratrol, due to safety concerns, and
terminated the study on December 2, 2010.
[105]

Sirtris Pharmaceuticals, which U.K.
-
based
GlaxoSmith
Kline bought for $720 million in 2008, was developing the drug. GlaxoSmithKline is now
focusing its efforts on more potent and selective SIRT1 activators

SRT2104 and SRT2379

both of
which are involved in several exploratory clinical trials.
[
citation needed
]

Full formal pharmacokinetics of oral resveratrol 2000

mg twice daily in humans, studying interaction
with concurrent ethanol, quercetin, and fat meal
has been published.
[106]

Mean peak serum
resveratrol concentration was 1274

ng/ml at steady
-
state, which was reduced 46% by a fat meal at
dosing. There was no effect o
f concurrent oral quercetin or ethanol. Healthy volunteers had
frequently reported minor diarrhea, and laboratory measures identified slight changes in liver function
tests and in serum potassium. No adverse effect on renal function was identified, althoug
h only eight
healthy adults were observed in the two
-
week study.

In humans and rats less than 5% of the oral dose was observed as free resveratrol in blood
plasma.
[39]
[104]

[41]
[107]
[108]

The most abundant resveratrol metabolites in humans, rats, and mice
are

trans
-
resveratrol
-
3
-
O
-
glucuronide

and trans
-
resveratrol
-
3
-
sulfate.
[109]
Walle suggests sulfate
conjugates are the primary
source of activity,
[104]

Wang et al. suggests the glucuronides,
[110]

and
Boocock et a
l. also emphasized the need for further study of the effects of the

metabolites
, including
the possibility of deconjugation to free resveratrol inside cells. Goldberd, who studied
the

pharmacokinetics

of resveratrol,

catechin

and

quercetin

in humans, concluded "it seems that the
potential health benefits of these compounds based upon the in vitro activities of the unconjugated
compounds are unrealistic and have been greatly exaggerated. Indeed, the profusion of papers
d
escribing such activities can legitimately be described as irrelevant and misleading. Henceforth,
investigations of this nature should focus upon the potential health benefits of
their

glucuronide
and

sulfate

conjugates."
[111]

The hypothesis that resveratrol from wine could have
higher bioavailability than resveratrol from a
pill

[12]
[112]

has been refuted
by experimental data.
[111]
[113]

For example, after five men took 600 ml of
red

wine with the resveratrol content of 3.2

mg/l (total dose about 2

mg) before breakfast, unchanged
resveratrol was detected in the blood of only two of them, and only in trace amounts (below
2.5

ng/ml). Resveratrol levels appeared to be slightly higher if
red wine (600 ml of red wine
containing 0.6

mg/ml resveratrol; total dose about 0.5

mg) was taken with a meal: trace amounts (1

6

ng/ml) were found in four out of ten subjects.
[113]

In another study, the pharmacokinetics of
resveratrol (25

mg) did not change whether it was taken with vegetable juice, white wine, or white
grape juice. The highest level of unchanged resveratrol in the

serum

(7

9

ng/ml) was achieved after
30 minutes, and it completely disappeared from blood after four hours.
[111]

The authors of
both
studies concluded the trace amounts of resveratrol reached in the blood are insufficient to explain the
French paradox. The beneficial effects of wine apparently could be explained by the effects of
alcohol

[111]

or the whole complex of substances wine contains;
[113]

for example, the cardiovascular
benefits of wine appear to co
rrelate with the content of
procyanidins
.
[114]

Adverse effects and unknowns

Long
-
term effects of using resveratrol are currently unknown.
[10]

One study has theorized it may
stimulate the growth of human

breast cancer

cells, possibly because of resveratrol's chemical
structure, which is similar to a

phytoestrogen
.
[11]
[115]

Other studies have found
resveratrol intake is
inversely associated with breast cancer risk, however, and acts to slow the progression of breast
cancer that has been transplanted into mice.
[11
6]
[117]

Some studies suggest resveratrol slows the
development of blood vessels, which suppresses tumors, but also slows healing.
[118]

Citing the
evidence that resveratrol is

estrogen

antagonistic, some retailers of resveratrol advise that the
compound may int
erfere with oral contraceptives and that women who are pregnant or intending to
become pregnant should not use the product, while others advise that resveratrol should not be
taken by children or young adults under eighteen, as no studies have shown how it

affects their
natural development. A small study found a single dose of up to 5 g of

trans
-
resveratrol caused no
serious adverse effects in healthy volunteers.
[39]

Possible carcinogenicity

Resveratrol in common with other polyphenols, was found to be a strong

topoisomerase inhibitor
,
sharing similarities to
chemotherapeutic anticancer drugs, such
as

etoposide

and

doxorubicin
.
[119]
[120]

This may simultaneously contribute to both the potential
anticarcinogenic and carcinogenic properties of the substanc
e in given circumstances. Harmful
properties of resveratrol may be pronounced in the human fetus, as it has diminished detoxification
systems. Therefore, resveratrol as commonly sold combined with other "bioflavonoids", should not be
used by pregnant women
.
[121]

Mechanisms of action

See

Calorie
restriction#Sir2.2FSIRT1 and resveratrol

for the details of the debate on resveratrol,
calorie restriction and life extension.

The mechanisms of resveratrol's apparent effects on life extension are not fully understood, but they
appear to mimic several of
the
biochemical

effects of

calorie restriction
. Some studies indicates
resveratrol activates
Sirtuin 1 (SIRT1)
[122]

and PGC
-
1α and improves the functioning of
the

mitochondria
.
[31]

Other research calls into question the theory connecting resveratrol, SIRT1, and
calorie restriction.
[123]
[124]

In addition resveratrol's ability to directly activate sirtuin 1 has been called
into question.
[124]
[125]
[126]

A paper by Robb

et al.

discusses resveratrol action in cells. It reports a fourteen
-
fold increase in the
action of MnSOD (
SOD2
).
[1
27]
MnSOD reduces

superoxide

to

hydrogen peroxide

(H
2
O
2
), but H
2
O
2

is
not increased due to other
cellular activity. Superoxide O
2
-

is a byproduct of respiration in complexes
1 and 3 of the

electron transport chain
. It is "not highly toxic, [but] can ext
ract an electron from
biological membrane and other cell components, causing free radical chain reactions. Therefore it is
essential for the cell to keep superoxide anions in check."
[128]

MnSOD reduces superoxide and
thereby, confers resistance to

mitochondrial dysfunction
, permeability transition, and apoptotic death
in various diseases.
[129]

It has been implicated in lifespan extension, inhibits cancer, (e.g. pancreatic
cancer)

[130]
[131]

and provides resistance to

reperfusion injury

and irradiation
damage.
[132]
[133]
[134]

These
effects have also been observed with resveratrol. Robb et al. propose MnSOD is increased by the
pathway RESV → SIRT1 / NAD+ → FOXO3a → MnSOD. Resveratrol has been shown to cause
SIRT1 to cause migration of FOXO transc
ription factors to the nucleus,
[135]

which stimulates FOXO3a
transcriptional activity

[136]

and it has been shown to enhance the sirtuin
-
catalyzed deacetylation
(activity) of
FOXO3a
. MnSOD is known to be a target of FOXO3a, and MnSOD expression is strongly
induced in cel
ls overexpressing FOXO3a.
[137]

Resveratrol interferes with all three stages of

carcinogenesis

initiation, promotion and progression.
Experiments in

cell cultures

of varied types and isolated subcellular systems

in vitro

imply many
mechanisms in the

pharmacological

activity of resveratrol. These mechanisms include modulation of
the

transc
ription factor

NF
-
κB
,
[138]

inhibition of the

cytochrome P450

isoenzyme

CYP1A1
[139]
(although
this may not be relevant to
the CYP1A1
-
mediated bioactivation of the
procarcinogen

benzo(a)pyrene
),
[140]

alteration
s in
androgenic

[141]

actions, and expression and activity
of

cyclooxygenase

(COX) enzymes. In vitro, resveratrol "inhibited the proliferation of human
pancreatic cancer cell lines." In some lineages of cancer

cell culture
, resveratrol has been shown to
induce apoptosis, which means it kills cells and may kill cancer cells.
[141]
[142]
[143]
[144]
[145]
[146]

Resveratrol
has been shown to induce Fas/Fas

ligand

mediated apoptosis,

p53

and

cyclins

A, B1, and

cyclin
-
dependent kinases

cdk 1 and 2. Resveratrol also possesses

antioxidant

and anti
-
angiogenic

properties.
[118]
[147]
[148]

Resveratrol was reported to be effective against

neuronal

cell dysfunction and cell
death, and, in
theory, could be effective against diseases such as

Huntington's disease

and Alzheimer's
disease.
[149]
[150]

Again, this has not yet been tested in humans for any disease.

Research at the

Northeastern Ohio Universities College of Medicine

and

Ohio State
University

indicated resveratrol has direct inhibitory action on cardiac fibroblasts, and may inhibit the
progression of

cardiac

fibrosis
.
[151]

Resveratrol also significantly increases natural

testosterone

production from being both a

selective
estrogen receptor modulator

[96]
[152]
and an

aromatase inhibitor
.
[153]
[154]

In December 2007, work from Irfan Rahman's laboratory at the

University of Rochester

demonstrated
resveratrol increased intracellular glutathione levels via Nrf2
-
dependent upregulation of

gamma
-
glutamylcysteine

ligase in lung epithelial cells, which protected them against cigarette smoke extract
-
induced oxidative stress.
[155]

Another potentially important mechanism common to both resveratrol supplementation and caloric
restriction is the modulation of
autophagy

[156]

SIRT1 is a hypothesized target of both resveratrol and
caloric restriction, and has been shown to facilitate autophag
y through the inhibition of mTOR, which
itself negatively regulates autophagy.
[157]

In 2012, it was shown that resveratrol is capable of competitively inhibiting
vario
us

phosphodiesterases
, which results in an increase in cytosolic concentration of

cAMP
, which
acts as a

second messenger

for the activation of the pathway
Epac1
/
CaMKKβ
/
AMPK
/
SIRT1
/
PGC
-

.
This rise of cAMP concentration allows an increase in oxidation of fatty acids, mitochondrial
biogenesis, mitocho
ndrial respiration, and gluconeogenesis.
[158]
[159]

[
edit
]
Chemical and physical properties

Resveratrol (3,5,4'
-
trihydroxystilbene) is a stilbenoid, a derivate of

stilbene
.

It exists as two

geometric isomers
:

cis
-

(
Z
) and

trans
-

(
E
), with the

trans
-
isomer

shown in the top
image. The

trans
-

and

cis
-
resveratrol can be either free or bound to glucose.
[160]

The

trans
-

form can
undergo isomerisation to the

cis
-

form when exposed t
o

ultraviolet
irradiation.
[161]

Trans
-
resveratrol in
the powder form was found to be stable under "accelera
ted stability" conditions of 75% humidity and
40

°C in the presence of air.
[162]

Resveratrol content also was stable in the skins of grapes
and

pomace

taken after fermentation and stored for a long period.
[163]

l
H
-

and

13
C
-
NMR data for the
four most common forms of
resveratrols are reported in literature.
[160]

Metabolism

Biosynthesis

Resveratrol is produced in plants with the help of the enzyme,

resveratrol synthase
.
[164]

Biotransformation

The grapevine fungal

pathogen

Botrytis cinerea

is able to oxidise resveratrol into metabolites
showing attenuated a
ntifungal activities. Those include the resveratrol dimers

restrytisol A
,

B
,
and

C
,

resveratrol trans
-
dehydrodimer
,

leachinol F
, and

pallidol
.
[165]

The soil bacterium

Bacillus cereus

can be used to transform resveratrol into

piceid

(resveratrol 3
-
O
-
beta
-
D
-
glucoside
).
[166]

Occurrences

In plants

Resveratrol was originally isolated by Takaoka from the roots of
hellebore in 1940, and later, in 1963,
from the roots of Japanese knotweed. It attracted wider attention only in 1992, however, when its
presence in wine was suggested as the explanation for cardioprotective effects of wine.
[12]

In grapes,

trans
-
resveratrol is a phytoalexin produced against the growth of fungal pathogens such
as

Botrytis cinerea
.
[167]

Its presence in

Vitis vinifera

grapes can also be constitutive, with
accumulation in ripe berries of different levels of bound and free resveratrols, according to the
genotype.
[168]

In grapes, resveratrol is found primarily in the skin,
[169]

and, in

muscadine

grapes,

also
in the seeds.
[170]

The amount found in grape skins also varies with the grape cultivar, its geographic
origin, and exposure to fungal infection. The amount of ferment
ation time a wine spends in contact
with grape skins is an important determinant of its resveratrol content.
[160]
[169]

In foods

The levels of resveratrol found in food varies greatly. Red wine contains between 0.2 and
5.8

mg/l,
[171]

depending on the grape
variety, while white wine has much less, because red wine
is

fermented

with the skins, allowing the wine to extract the resveratrol, whereas
white wine

is
fermented after the skin has been removed.
[169]
[172]

The composition of wine is different from that of
grapes since the extraction of resveratrols from grapes depends on the duration of the skin contact,
and the resveratrol 3
-
glucosides are in part hydrolised, yielding both

trans
-

an
d

cis
-
resveratrol.
[160]

A
number of reports have indicated muscadine grapes may contain high concentrations of resveratrol,
and that wines produced from these grapes, both re
d and white, may contain more than
40

mg/l,
[170]
[173]
however, subsequent studies have
found little or no resveratrol in different varieties of
muscadine grapes.
[174]
[175]

One of

the most promising sources is

peanuts
, especially

sprouted

peanuts where the content rivals
that in grapes. Before sprout
ing, it was in the range of 2.3 to 4.5 μg/g, and after sprouting, in the
range of 11.7 to 25.7 μg/g depending upon peanut cultivar.
[176]

The fruit of the

mulberry

(esp. the skin)
[177]

is a source, and is sold as a nutritional supplement.

Cocoa powder
,

baking chocolate
, and

dark chocolate

also have low levels of resveratrol in normal
consumption quantities (0.35 to 1.85

mg/kg).
[178]

Of growing importance is Japanese knotwee
d, which is being used by some manufacturers for its
high level of resveratrol.
[179]

[
edit
]
Content in wines and grape juice

Beverage

Total resveratrol (mg/l)
[169]
[170]

Total resveratrol (mg/150ml)
[169]
[170]

Red wine (global)

1.98


7.13

0.30


1.07

Red wine (Spanish)

1.92


12.59

0.29


1.89

Red grape juice (Spanish)

1.14


8.69

0.17


1.30

Rose wine (Spanish)

0.43


3.52

0.06



0.53

Pinot noir

0.40


2.0

0.06


0.30

White wine (Spanish)

0.05


1.80

0.01


0.27

The

trans
-
resveratrol concentration in 40 Tuscan wines ranged from 0.3 to 2.1

mg/l in the 32
red
wines tested and had a maximum of 0.1

mg/l in the 8 white wines in the test. Both the

cis
-

and

trans
-
isomers of resveratrol were detected in all tested samples.

cis
-
resveratrol levels were comparable to
those of the

trans
-
isomer. They ranged from 0.5

m
g/l to 1.9

mg/l in red wines and had a maximum of
0.2

mg/l in white wines.
[180]

In a review of published resveratrol concentrations, the average in red wines is 1.9 ± 1.7

mg
trans
-
resveratrol/L (8.2 ± 7.5 μM), ranging from nondetectable levels to 14.3

mg/l (62.7 μM)

trans
-
resveratrol. Levels of

cis
-
resveratrol follow the same trend as

trans
-
resveratrol.
[181]

Reports suggest some aspect of the wine making process converts piceid to resveratrol in wine, as
wine seems to have twice the average resveratrol concentration of the equivalent commercial
juices.
[170]

In general, wines made from grapes of the Pinot Noir and St. Laurent varieties showed the highest
level of

trans
-
resveratrol, though no wine or region can yet be said t
o produce wines with significantly
higher concentrations than any other wine or region.
[181]

[
edit
]
Content in selected foods

Food

Serving

Total resveratrol (mg)
[178]
[182]

Peanuts (raw)

1 c (146 g)

0.01


0.26

Peanuts (boiled)

1 c (180 g)

0.32


1.28

Peanut butter

1 c (258 g)

0.04


0.13

Red grapes

1 c (160 g)

0.24


1.25

Cocoa powder

1

c (200 g)

0.28


0.46

Ounce for ounce, peanuts have about half as much resveratrol as red wine. The average amount in
peanuts in the marketplace is 79.4

µg/ounce.

In comparison, some red wines contain approximately 160

µg/fluid ounce.
[183]

Resveratrol was
detected in grape, cranberry, and wine samples. Concentrations ranged from 1.56 to 1042 nmol/g in
Concord grape products, and from 8.63 to 24.84

µmol/L in
Italian red wine. The concentrations of
resveratrol were similar in cranberry and grape juice at 1.07 and 1.56 nmol/g, respectively.
[184]

Blueberries

have about twice as much resveratrol as

bilberries
, but there is great regional variation.
These fruits have less than 10% of the resveratrol o
f grapes. Cooking or heat processing of these
berries will contribute to the degradation of resveratrol, reducing it by up to half.
[185]

Supplementation

As a result of extens
ive news coverage,
[186]
[187]

sales of supplements greatly increased in
2006.
[188]

This was despite the existence of studies cautioning that benefits to humans are
unproven.
[1
88]
[189]
[190]

Supplements vary in purity and can contain anywhere from 50 percent to 99 percent resverat
rol.
Many brands consist of an unpurified extract of Japanese knotweed (
Polygonum cuspidatum
),
an

introduced species

in many countries. These contain about 50 percent
resveratrol by weight, as
well as

emodin
, which, while considered safe in moderate quantities, can have a

laxative effect

in

high amounts.
[191]

Resveratrol can be produced from its glucoside piceid from Japanese knotweed
fermented by

Aspergillus oryzae
.
[15]

Harvard University

scientist and profes
sor,

David Sinclair
, is often quoted in online ads, however,
Sinclair, who has studied resveratrol extensively, has gone on record in

Bloomberg Businessweek

to
say he never uttered many of the statements attributed to him on these sites.
[192]

[
edit
]
Related compounds



Dihydro
-
resveratrol



Epsilon
-
viniferin

and

Pallidol
, two different resveratrol dimers



Trans
-
diptoindonesin B
, a resveratrol trimer



Hopeaphenol
, a resveratrol tetramer



Oxyresveratrol
, the aglycone of

mulberroside A
, a compound found in

Morus alba
, the white
mulberry
[193]



Piceatannol
, an active metabolite of resveratrol found in red wine



Piceid
, a resveratrol glucoside



Pterostilbene
, a doubly methylated resveratrol



4'
-
Methoxy
-
(E)
-
resveratrol 3
-
O
-
rutinoside
, a compound found in the stem bark of

Boswellia
dalzielii
[194]

See also


Pharmacy and Pharmacology portal



Phenolic compounds in wine



Polyphenol antioxidant



Wine and health

References

1.

^

a

b

Camont, L; Cottart, C; Rhayem, Y; Nivetantoine, V; Djelidi, R; Collin, F; Beaudeux, J;
Bonnefontrousselot, D (2009). "Simple spectrophotometric assessment of the trans
-
/cis
-
r
esveratrol ratio in aqueous solutions".

Analytica Chimica Acta
634

(1): 121

8.

doi
:
10.1016/j.aca.2008.12.003
.
PMID

19154820
.

2.

^

a

b

Resveratrol MSDS on Fisher Scientific website

3.

^

a

b

c

Resveratrol MSDS on www.sigmaaldrich.com

4.

^

Bechmann, LP; Zahn, D; Gieseler, RK; Fingas, CD; Marquitan, G; Jochum, C; Gerken, G;
Friedman, SL et al. (2009).
"Resveratrol amplifies profibrogenic effects of free fatty acids on
human hepatic stellate cells"
.

Hepatology research

: the official journal of the Japan Society of
Hepatology

39

(6): 601

8.
doi
:
10.1111/j.1872
-
034X.2008.00485.x
.

PMC

2893585
.
PMID

19207580
.

5.

^

a

b

Bass TM, Weinkove D, Houthoofd K, Gems D, Partridge L (October
2007). "Effects of
resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans".

Mech. Ageing
Dev.

128

(10): 546

52.

doi
:
10.1016/j.mad.2007.07.007
.
PMID

17875315
.

6.

^

"Micronutrient Information Center: Resveratrol"
. Linu
s Pauling Institute at Oregon State
University
. Retrieved 2012
-
01
-
13
.

7.

^

a

b

Elliott PJ, Jirousek M (April 2008). "Sirtuins: novel targets for metabolic disease".

Curr Opin
Investig Drugs

9

(4): 371

8.
PMID

18393104
.

8.

^

"Sirtris Announces Positive Results with Proprietary Version of Resveratrol, SRT501, in a
Phase
1b Type 2 Diabetes Clinical Study
-

Drugs.com MedNews"
.

Press Release
. Drugs.com.
2008
-
01
-
07
. Retrieved 2012
-
02
-
22
.

9.

^

"Pharma seeks genetic clues to healthy aging"
.

Reuters
. 6 April 2010.

10.

^

a

b

The Connecticut Post, "Selling resveratrol: Wonder drug or snake oil?," 08/04/2009, by
Melissa Healy for the Los Angeles Times news service

11.

^

a

b

Gehm BD, McAndrews JM, Chien PY, Jameson JL (December 1997).

"Resveratrol, a
polyphenolic compound found in grapes and wine, is an agonist for the estrogen re
ceptor"
.

Proc.
Natl. Acad. Sci. U.S.A.

94

(25): 14138

43.
doi
:
10.1073/pnas.94.25.14138
.

PMC

28446
.
PMID

9391166
.

12.

^

a

b

c

d

Baur JA, Sinclair DA (June 2006). "Therapeutic potential of resveratrol: the

in vivo
evidence".

Nat Rev Drug Discov

5

(6): 493

506.

doi
:
10.1038/nrd2060
.

PMID

16732220
.

13.

^

Farina

A, Ferranti C, Marra C (March 2006). "An improved synthesis of resveratrol".

Nat. Prod.
Res.

20

(3): 247

52.
doi
:
10.1080/14786410500059532
.

PMID

16401555
.

14.

^

Trantas E, Panopoulos N, Ververidis F (November 2009).
"Metabolic engineering of the
complete pathway leading to heterologous biosynthesis of various flavonoids and stilbenoids
in
Saccharomyces cerevisiae".

Metab. Eng.

11

(6): 355

66.

doi
:
10.1016/j.ymben.2009.07.004
.
PMID

19631278
.

15.

^

a

b

Wang, H.; Liu, L.; Guo, Y.
-
X.; Dong, Y.
-
S.; Zhang, D.
-
J.; Xiu, Z.
-
L. (2007).
"Biotransformation of piceid in Polygonum cuspidatum to resveratrol by Aspergillus
oryzae".

Applie
d Microbiology and Biotechnology

75

(4): 763

8.
doi
:
10.1007/s00253
-
007
-
0874
-
3
.

PMID

17333175
.

16.

^

Resveratrol, a new ph
enolic compound, from Veratrum grandiflorum. M Takaoka, Journal of
the Chemical Society of Japan, 1939, volume 60, pages 1090
-
1100 (
abstract
)

17.

^

Schröder, Joachim (March 6, 2010).

"Discovery of resveratrol"
.

Res
veratrol
.
[
self
-
published source?
]

18.

^

Howitz KT, Bitterman KJ, Cohen HY, Lamming DW,
Lavu S, Wood JG, Zipkin RE, Chung P,
Kisielewski A, Zhang LL, Scherer B, Sinclair DA (September 2003). "Small molecule activators of
sirtuins extend Saccharomyces cerevisiae lifespan".

Nature

425

(6954): 191

6.
doi
:
10.1038/nature01960
.

PMID

12939617
.

19.

^

Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D (August 2004). "Sirtuin
activato
rs mimic caloric restriction and delay ageing in metazoans".

Nature

430

(7000): 686

9.

doi
:
10.1038/nature02789
.

PMID

15254550
.

20.

^

Gruber J, Tang SY, Halliwell B (April 2007). "Evidence for a trade
-
off between survival and
fitness caused by resveratrol treatment of Caenorhabditis elegans".

Ann. N. Y. Acad. Sci.
1100
:
530

42.

doi
:
10.1196/annals.1395.059
.
PMID

17460219
.

21.

^

Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, Cellerino A (February 2006).
"Resveratrol prolongs lifespan and retards the onset of age
-
related markers in a short
-
lived
vertebrate".

Curr. Biol.

16

(3): 296

300.
doi
:
10.1016/j.cub.2005.12.038
.

PMID

16461283
.

22.

^

a

b

Baur JA, Pea
rson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS,
Lopez
-
Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M,
Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P,
Puigserver P, Ingra
m DK, de Cabo R, Sinclair DA (November 2006). "Resveratrol improves
health and survival of mice on a high
-
calorie diet".

Nature

444
(7117): 337

42.

doi
:
10.1038/nature05354
.
PMID

17086191
.

23.

^

a

b

Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR,
Kamara
D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA,
Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari
Z, Sinclair DA, de Cabo R (August 2008).

"Resveratrol delays age
-
related deterioration and
mimics transcriptional aspects of dietary restriction without extending life span"
.

Cell
Metab.

8

(2): 157

68.

doi
:
10.1016/j.cmet.2008.06.011
.

PMC

2538685
.
PMID

18599363
.

24.

^

Miller RA, Harrison DE, Astle CM, Floyd RA, Flurkey K, Hensley KL, Javors MA,
Leeuwenburgh C, Nelson JF, Ongini E, Nadon NL, Warner HR, Strong R (August 2007). "An
Aging Interventions Te
sting Program: study design and interim report".

Aging Cell

6
(4): 565

75.

doi
:
10.1111/j.1474
-
9726.2007.00311.x
.
PMID

17578509
.

25.

^

a

b

Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R, Fernandez E, Flur
key K,
Javors MA, Nelson JF, Orihuela CJ, Pletcher S, Sharp ZD, Sinclair D, Starnes JW, Wilkinson JE,
Nadon NL, Strong R (February 2011).
"Rapamycin, but not resveratrol or simvastatin, ex
tends life
span of genetically heterogeneous mice"
.

J. Gerontol. A Biol. Sci. Med. Sci.

66

(2): 191

201.

doi
:
10.1093/gerona/glq178
.
PMC

3021372
.

PMID

20974732
.

26.

^

"'Longevity gene' may be dead end: study"
.

Agence France
-
Presse
.

The Raw Story
.
September 12, 2011.

27.

^

Ledford, Heidi (2011). "Longevity genes challenged".

Nature
.
doi
:
10.1038/news.2011.549
.

28.

^

Viswanathan M, Guarente L (September 2011). "Regulation of Caenorhabditis elegans lifespan
by sir
-
2.1 transgenes".

Nature
477

(7365): E1

2.

doi
:
10.1038/nature10440
.
PMID

21938026
.

29.

^

Lombard DB, Pletcher SD, Cantó C, Auwerx J (September 2011). "Ageing: longevity hits a
roadblock".

Nature

477

(7365): 410

1.

doi
:
10.1038/477410a
.

PMID

21938058
.

30.

^

Wade, Nicholas (November 16, 2006).

"Red Wine Ingredient Increases Endurance, Study
Shows"
.

New York Times
.

31.

^

a

b

c

Lagouge M, Argmann C, Gerhart
-
Hines Z, Meziane H, Lerin C, Daussin F, Messadeq

N,
Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (December 2006).
"Resveratrol improves mitochondrial function and protects against metabolic disease by
activating SIRT1 and PGC
-
1alpha".

Cell

127

(6): 1109

22.
doi
:
10.1016/j.cell.2006.11.013
.

PMID

17112576
.

32.

^

Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR,

Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM (January 1997). "Cancer chemopreventive
activity of resveratrol, a natural product derived from grapes".
Science

275

(5297): 218

20.
doi
:
10.1126/science.275.5297.218
.

PMID

8985016
.

33.

^

Lin, KH; Hsiao, G; Shih, CM; Chou, DS; Sheu, JR (2009). "Mechanisms of resveratrol
-
induced
platelet

apoptosis".
Cardiovascular research

83

(3): 575

85.
doi
:
10.1093/cvr/cvp139
.

PMID

19423619
.

34.

^

Wang Z
, Huang Y, Zou J, Cao K, Xu Y, Wu JM (January 2002). "Effects of red wine and wine
polyphenol resveratrol on platelet aggregation in vivo and in vitro".

Int. J. Mol. Med.

9

(1): 77

9.
PMID

11745001
.

edit

35.

^

a

b

Zou J, Huang Y, Chen Q,
Wang N, Cao K, Hsieh TC, Wu JM (October 1999). "Suppression
of mitogenesis and regulation of cell cycle traverse by resveratrol in cultured smooth muscle
cells".

Int. J. Oncol.

15

(4): 647

51.

PMID

10493944
.

edit

36.

^

Brito PM, Devillard R, Nègre
-
Salvayre A, Almeida LM, Dinis TC, Salvayre R, Augé N (July
2009). "Resveratrol inhibits the mTOR mitogenic signaling evoked by oxidized LD
L in smooth
muscle cells".

Atherosclerosis

205

(1): 126

34.
doi
:
10.1016/j.atherosclerosis.2008.11.011
.
PMID

19108833
.

edit

37.

^

a

b

c

d

e

f

Athar M, Back JH, Tang X, Kim KH, Kopelovich L, Bickers DR,

Kim AL (November
2007).

"Resveratrol: a review of preclinical studies for human cancer prevention"
.

Toxicol. Appl.
Pharmacol.

224

(3): 274

83.
doi
:
10.1016/j.taap.2006.12.025
.

PMC

2083123
.
PMID

173063
16
.

38.

^

Resveratrol
. From

Clinicaltrials.gov
. Retrieved August 15, 2008.

39.

^

a

b

c

d

Boocock DJ, Faust GE, Patel KR, Schinas AM, Brown VA, Ducharme MP, Booth TD,
Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE (June 2007). "Phase I dose
escalation pharmacokinetic study in healthy volunteers of resveratrol, a potent
ial cancer
chemopreventive agent".

Cancer Epidemiol. Biomarkers Prev.

16

(6): 1246

52.
doi
:
10.1158/1055
-
9965.EPI
-
07
-
0022
.

PMID

17548692
.

40.

^

Niles RM, Cook CP, Meadows GG, Fu YM, McLaughlin JL, Rankin GO (October
2006).

"Resveratrol is rap
idly metabolized in athymic (nu/nu) mice and does not inhibit human
melanoma xenograft tumor growth"
.

J. Nutr.

136

(10): 2542

6.
PMC

1612582
.

PMID

16988123
.

41.

^

a

b

Wenzel E, Soldo T, Erbersdobler H, Somoza V (May 2005). "Bioactivity and metabolism of
trans
-
resveratrol orally administered to Wistar rats".

Mol Nutr Food Res

49

(5): 482

94.
doi
:
10.
1002/mnfr.200500003
.

PMID

15779067
.

42.

^

Li ZG, Hong T, Shimada Y, Komoto I, Kawabe A, Ding Y, Kaganoi J, Hashimoto Y, Imamura M
(September 2002). "Suppression of N
-
nitrosomethylbenzylamine (NMBA)
-
induced eso
phageal
tumorigenesis in F344 rats by resveratrol".
Carcinogenesis

23

(9): 1531

6.
doi
:
10.109
3/carcin/23.9.1531
.

PMID

12189197
.

43.

^

Gao X, Xu YX, Divine G, Janakiraman N, Chapman RA, Gautam SC (July 2002). "Disparate in
vitro and in vivo antileukemic effects of resveratrol, a natural polyphenolic c
ompound found in
grapes".

J. Nutr.

132

(7): 2076

81.
PMID

12097696
.

44.

^

Kimura Y, Okuda H (June 2001).
"Resveratrol isolated from Polygonum cuspidatum root
prevents tumor growth and metastasis to lung and tumor
-
induced neovascularization i
n Lewis
lung carcinoma
-
bearing mice".

J. Nutr.

131

(6): 1844

9.
PMID

11385077
.

45.

^

Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, Wang Y, Raederstorff D, Morrow
JD, Leeuwenburgh C, Allison DB, Saupe KW, Cartee GD, Weindruch R, Prolla TA (2008
). Tomé,
Daniel. ed.

"A low dose of dietary resveratrol partially mimics caloric restriction and retards aging
parameters in mice"
.

PLoS ONE

3

(6):
e2264.
doi
:
10.1371/journal.pone.0002264
.

PMC

2386967
.
PMID

18
523577
.

46.

^

Szmitko PE, Verma S (January 2005). "Cardiology patient pages. Red wine and your
heart".

Circulation

111

(2): e10

1.
doi
:
10.1161/01.CIR.0000151608.29217.62
.
PMID

15657377
.

47.

^

Ferrières J (January 2004).

"The French paradox: lessons for other countries"
.

Heart

90

(1):
107

11.
doi
:
10.1136/heart.90.1.107
.

PMC

1768013
.
PMID

14676260
.

48.

^

Simini B (January 2
000). "Serge Renaud: from French paradox to Cretan
miracle".

Lancet

355

(9197): 48.
doi
:
10.1016/S0140
-
6736(05)71990
-
5
.

PMID

106158
98
.

49.

^

Renaud S, de Lorgeril M (June 1992).
"Wine, alcohol, platelets, and the French paradox for
coronary heart disease".
Lancet

339

(8808): 1523

6.

doi
:
10.1016/0140
-
6736(92)91277
-
F
.

PMID

1351198
.

50.

^

Kopp P (J
une 1998). "Resveratrol, a phytoestrogen found in red wine. A possible explanation
for the conundrum of the 'French paradox'?".

Eur. J. Endocrinol.

138

(6): 619

20.
doi
:
10.1530/eje.0.1380619
.

PMID

9678525
.

51.

^

Ferrero ME, Bertelli AE, Fulgenzi A, Pellegatta F, Corsi MM, Bonfrate M, Ferra
ra F, De
Caterina R, Giovannini L, Bertelli A (December 1998).
"Activity in vitro of resveratrol on
granulocyte and monocyte adhesion to endothelium".

Am. J. Clin. Nutr.

68
(6): 1208

14.

PMID

9846848
.

52.

^

Rotondo
S, Rajtar G, Manarini S, Celardo A, Rotillo D, de Gaetano G, Evangelista V, Cerletti C
(April 1998).

"Effect of trans
-
resveratrol, a natural polyphenolic compound, on human
polymorphonucl
ear leukocyte function"
.

Br. J. Pharmacol.

123
(8): 1691

9.

doi
:
10.1038/sj.bjp.0701784
.

PMC

1565338
.
PMID

9605577
.

53.

^

Haider UG, Roos TU, Kontaridis MI, Neel BG, Sorescu D, Griendling KK, Vollmar AM, Dirsch
VM (July 2005).

"Resveratrol inhibits angiotensin II
-

and epidermal growth factor
-
mediated Akt
activation: role of Gab1 and Shp2".

Mol. Pharmacol.

68

(1): 41

8.

doi
:
10.1124/mol.104.005421
.

PMID

15849355
.

54.

^

Wang Z, Chen Y, Labinskyy N, Hsieh TC, Ungvari Z, Wu JM (July 2006). "Regulation of
proliferation and gene expression in cultured human aortic smooth muscle cells by resveratrol
and standardized grape extracts".

Biochem. Biophys. Res. Commun.

346

(1): 367

76.

doi
:
10.10
16/j.bbrc.2006.05.156
.
PMID

16759640
.

55.

^

Poussier B, Cordova AC, Becquemin JP, Sumpio BE (December 2005). "Resveratrol inhibits
vascular smooth muscle cell proliferation and induces apoptosis".

J. Vasc. Surg.
42

(6): 1190

7.

doi
:
10.1016/j.jvs.2005.08.014
.
PMID

16376213
.

56.

^

Duffy SJ, Vita JA (February 2003). "Effects of
phenolics on vascular endothelial function".

Curr.
Opin. Lipidol.

14

(1): 21

7.
doi
:
10.1097/01.mol.0000052857.26236.f2
.
PMID

12544657
.

57.

^

Wallerath T, Deckert G, Ternes T, Anderson H, Li H, Witte K, Förstermann U (September
2002). "Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and
activity of endothelial nitric oxide synthase"
.

Circulation

106

(13): 1652

8.

doi
:
10.1161/01.CIR.0000029925.18593.5C
.
PMID

12270858
.

58.

^

Chen CK
, Pace
-
Asciak CR (March 1996). "Vasorelaxing activity of resveratrol and quercetin in
isolated rat aorta".

Gen. Pharmacol.

27

(2): 363

6.

doi
:
10.1016/0306
-
3623(95)02001
-
2
.

PMID

8919657
.

59.

^

Olas B, Wachowicz B (August 2005). "Resveratrol, a phenolic antioxidant with effects on blood
platelet functions".

Platelets

16
(5): 251

60.

doi
:
10.1080/09537100400020591
.
PMID

16011975
.

60.

^

Stef G, Csiszar A, Lerea K, Ungvari Z, Veress G (August 2006).
"Resveratrol inhibits
aggregation of platelets from high
-
risk cardiac patients with aspirin resistance".

J. Cardiovasc.
Pharmacol.

48

(2): 1

5.
doi
:
10.1097/01.fjc.0000238592.67191.ab
.

PMID

16954814
.

61.

^

Wang Z, Zou J, Huang Y, Cao K, Xu Y, Wu JM (March 2002).
"Effect of resveratrol on platelet
aggregation in vivo and in vitro"
.

Chin. Med. J.

115

(3): 378

80.

PMID

11940369
.

62.

^

The red wine phenolicstrans
-
resveratrol and quercetin block human platelet aggregation
and

eicosanoid

synthesis: Implications for protection against

coronary heart disease
. Cecil R.

Pace
-
Asciak, Susan Hahn, Eleftherios P. Diamandis, George Soleas and David M. Goldberg,
Clinica Chimica Acta, 31 March 1995, Volume 235, Issue 2, Pages 207

219,

doi
:
10.1016/0009
-
8981(95)06045
-
1

63.

^

Frémont L, Belguendouz L, Delpal S (1999). "Antioxidant

activity of resveratrol and alcohol
-
free
wine polyphenols related to LDL oxidation and polyunsaturated fatty acids".

Life Sci.

64
(26):
2511

21.

doi
:
10.1016/S0024
-
3205(99)00209
-
X
.
PMID

1040351
1
.

64.

^

Ungvari Z, Orosz Z, Rivera A, Labinskyy N, Xiangmin Z, Olson S, Podlutsky A, Csiszar A (May
2007). "Resveratrol increases vascular oxidative stress resistance".

A
m. J. Physiol. Heart Circ.
Physiol.

292

(5): H2417

24.
doi
:
10.1152/ajpheart.01258.2006
.

PMID

17220179
.

65.

^

Das
DK, Maulik N (February 2006). "Resveratrol in cardioprotection: a therapeutic promise of
alternative medicine".
Mol. Interv.

6

(1): 36

47.

doi
:
10.1124/mi.6.1.7
.
PMID

16507749
.

66.

^

Investigation Finds UConn Professor Fabricated Rese
arch
-

Work Focused On Resveratrol,
Chemical In Red Wine
Hartford Courant
, January 11, 2012)

67.

^

Retraction Watch

68.

^

Lamont KT, Somers S, Lacerda L, Opie LH, Lecour S (May 2011). "Is red wine a SAFE sip
away from cardioprotection? Mechanisms involved in resveratrol
-

and melatonin
-
induced
cardioprotection".

J. Pineal Res.

50

(4): 374

80.
doi
:
10.1111/j.1600
-
079X.2010.00853.x
.

PMID

21342247
.

69.

^

Su HC, Hung LM, Chen JK (June 2006). "Resveratrol, a
red wine antioxidant, possesses an
insulin
-
like effect in streptozotocin
-
induced diabetic rats".

Am. J. Physiol. Endocrinol.
Metab.

290

(6): E1339

46.
doi
:
10.1152/ajpendo.00487.2005
.

PMID

16434553
.

70.

^

Deng JY, Hsieh PS, Huang JP, Lu LS, Hung LM (July 2008).
"Activation of estrogen receptor is
crucia
l for resveratrol
-
stimulating muscular glucose uptake via both insulin
-
dependent and
-
independent pathways"
.

Diabetes

57

(7): 1814

23.

doi
:
10.2337/db07
-
1750
.

PMC

2453636
.
PMID

18426865
.

71.

^

Palsam
y P, Subramanian S (November 2008). "Resveratrol, a natural phytoalexin, normalizes
hyperglycemia in streptozotocin
-
nicotinamide induced experimental diabetic rats".

Biomed.
Pharmacother.

62

(9): 598

605.
doi
:
10.1016/j.biopha.2008.06.037
.

PMID

18675532
.

72.

^

Sharma S, Anjaneyulu M, Kulkarni SK, Chopra K (2006). "Resver
atrol, a polyphenolic
phytoalexin, attenuates diabetic nephropathy in rats".

Pharmacology

76

(2): 69

75.
doi
:
10.1159/000089720
.

PMID

16286809
.

73.

^

Schmatz R, Mazzanti CM, Spanevello R, Stefanello N, Gutierres J, Corrêa M, da Rosa MM,
Rubin MA, Chitolina Schetinger MR, Morsch VM (May 2009). "Resveratrol prevents memory
deficits and the

increase in acetylcholinesterase activity in streptozotocin
-
induced diabetic
rats".

Eur. J. Pharmacol.

610

(1

3): 42

8.
doi
:
10.1016/j.ejphar.2009.03.032
.

PMID

19303406
.

74.

^

Penumathsa SV, Thirunavukkarasu M, Zhan L, Maulik G, Menon VP, Bagchi D, Maulik N
(December 2008). "Resveratrol enhances GLUT
-
4 translocation to the caveolar lipid raf
t fractions
through AMPK/Akt/eNOS signalling pathway in diabetic myocardium".

J. Cell. Mol. Med.

12

(6A):
2350

61.
doi
:
10.1111/j.1582
-
4934.2008.00251.x
.

PMID

18266981
.

75.

^

"Sirtris Announces SR
T501 Lowers Glucose in Twice
-
Daily Dosing Clinical Trial; Study
Suggests Dose Response for Proprietary Formulation of Resveratrol in Type 2 Diabetics"
(Press
release). Sirtris Pharmaceuticals. April 17, 2008
. Retrieved August 9, 2010
.

76.

^

"Sirtris Continues to Lead The Way In Resveratrol Based Research"
. My
Resveratrol
Experience. 2009
-
04
-
10
. Retrieved 2011
-
01
-
22
.

77.

^

Karuppagounder SS, Pinto JT, Xu H, Chen HL, Beal MF, Gibson GE (February 2009).

"Dietary
supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's
disease"
.

Neurochem. Int.

54

(2): 111

8.
doi
:
10.1016/j.neuint.2008.10.008
.

PMC

2892907
.
PMID

19041676
.

78.

^

Anekonda TS (September 2006). "Resveratrol
--
a boon for treating Alzheimer's
disease?".

Brain Res Rev

52

(2): 316

26.
doi
:
10.1016/j.brainresrev.2006.04.004
.

PMID

16766037
.

79.

^

Sharma M, Gupta YK (October 2002). "Chronic treatme
nt with trans resveratrol prevents
intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in
rats".

Life Sci.

71

(21): 2489

98.

doi
:
10.1016/S0024
-
3205(02)02083
-
0
.
PMID

12270754
.

80.

^

Kumar P, Padi SS, Naidu PS, Kumar A (September 2006).
"Effect of resveratrol on 3
-
nitropropionic acid
-
induced biochemical and behavioural changes: possible neuroprotective
mechanisms".

Behav Pharmacol

17

(5

6): 485

92.

doi
:
10.1097/00008877
-
200609000
-
00014
.
PMID

16940769
.

81.

^

Yang YB, Piao YJ (July 2003). "Effects of resveratrol on secondary damages after acute spinal
cord injury in rats".

Acta Pharmacol. Sin.

24

(7): 703

10.

PMID

12852839
.

82.

^

Sinha K, Chaudhary G, Gupta YK (June 2002). "Protective effect of resveratrol against
oxidative stress in middle cerebral artery occlusion model of stroke in rats".

Li
fe Sci.

71

(6): 655

65.

doi
:
10.1016/S0024
-
3205(02)01691
-
0
.

PMID

12072154
.

83.

^

Gentilli M, Mazoit JX,
Bouaziz H, Fletcher D, Casper RF, Benhamou D, Savouret JF (February
2001). "Resveratrol decreases hyperalgesia induced by carrageenan in the rat hind paw".

Life
Sci.

68

(11): 1317

21.

doi
:
10.1016/S0024
-
3205(00)01018
-
3
.

PMID

11233998
.

84.

^

Tsai SH, Lin
-
Shiau SY, Lin JK (February 1999).

"Suppression of nitric oxide synthase and the
down
-
regulation of the activation of NFkappaB in macrophages by resveratrol"
.

Br. J.
Pharmacol.

126

(3): 673

80.

doi
:
10.1038/sj.bjp.0702357
.
PMC

1565862
.

PMID

10188978
.

85.

^

Elmali N, Baysal O, Harma A, Esenkaya I, Mizrak B (April 2007). "Effects of resveratrol in
inflammatory arthritis".
Inflammation

30

(1

2): 1

6.

doi
:
10.1007/s10753
-
006
-
9012
-
0
.

PMID

17115116
.

86.

^

Docherty JJ, Fu MM, Stiffler BS, Limperos RJ, Pokabla CM, DeLucia AL (October 1999).
"Resveratrol inhibition of herpes simplex virus replication".

Antiviral Res.

43

(3): 145

55.
doi
:
10.1016/S0166
-
3542(99)00042
-
X
.

PMID

10551373
.

87.

^

Docherty JJ, Fu MM, Hah JM, Sweet TJ, Faith SA, Booth T (September 2005). "Effect of
resveratrol
on herpes simplex virus vaginal infection in the mouse".

Antiviral Res.

67

(3): 155

62.
doi
:
10.1016/j.antiviral.2005.06.008
.

PMID

161252
58
.

88.

^

Docherty JJ, Smith JS, Fu MM, Stoner T, Booth T (January 2004). "Effect of topically applied
resveratrol on cutaneous herpes simplex virus infections in hairless

mice".

Antiviral Res.
61

(1):
19

26.

doi
:
10.1016/j.antiviral.2003.07.001
.
PMID

14670590
.

89.

^

Docherty JJ, Sweet TJ, Bailey E, Faith SA, Booth T (December 2006). "Resveratrol inhibition of
varicella
-
zoster virus replication in vitro".

Antiviral Res.

72

(3): 171

7.
doi
:
10.1016/j.antiviral.2006.07.004
.

PMID

16899306
.

90.

^

Guan WD, Yang ZF, Liu N, Qin S, Zhang FX, Zhu YT (September 2008). "[In vitro experimental
study on the effect of resveratrol against
several kinds of respiroviruses]" (in Chinese).

Zhong
Yao Cai

31

(9): 1388

90.

PMID

19180966
.

91.

^

Palamara AT, Nencioni L, Aquilano K, De Chiara G, Hernandez L, Cozzolino F, Ciriolo MR,
Garaci E (May 2005).
"Inhibition of influenza A virus replication by resveratro
l".

J. Infect.
Dis.

191

(10): 1719

29.

doi
:
10.1086/429694
.
PMID

15838800
.

92.

^

Li YQ,

Li ZL, Zhao WJ, Wen RX, Meng QW, Zeng Y (September 2006). "Synthesis of stilbene
derivatives with inhibition of SARS coronavirus replication".

Eur J Med Chem

41

(9): 1084

9.
doi
:
10.1016/j.ejmech.2006.03.024
.

PMID

16875760
.

93.

^

Evers DL, Wang X, Huong SM, Huang DY, Huang ES (August 2004).

"3,4',5
-
Trihydroxy
-
trans
-
stilbene (resveratrol) inhibits human cytomegalovirus replication and virus
-
induced cellular
signaling".

Antiviral Res.

63

(2): 85

95.
doi
:
10.1016/j.antiviral.2004.03.002
.

PMID

15302137
.

94.

^

Heredia A, Davis C, Redfield R (November 2000). "Synerg
istic inhibition of HIV
-
1 in activated
and resting peripheral blood mononuclear cells, monocyte
-
derived macrophages, and selected
drug
-
resistant isolates with nucleoside analogues combined with a natural product,
resveratrol".

J. Acquir. Immune Defic. Synd
r.

25

(3): 246

55.

doi
:
10.1097/00126334
-
200011010
-
00006
.

PMID

11115955
.

95.

^

Shin
S, Jeon JH, Park D, Jang MJ, Choi JH, Choi BH, Joo SS, Nahm SS, Kim JC, Kim YB
(January 2008). "trans
-
Resveratrol relaxes the corpus cavernosum ex vivo and enhances
testosterone levels and sperm quality in vivo".

Arch. Pharm. Res.

31

(1): 83

7.

doi
:
10.1007/s12272
-
008
-
1124
-
7
.
PMID

18277612
.

96.

^

a

b

Juan ME, González
-
Pons E, Munuera T, Ballester J, Rodríguez
-
Gil JE, Planas JM (April
2005).
"trans
-
Resveratrol, a natural antioxidant from grapes, increases sperm outp
ut in healthy
rats".

J. Nutr.

135

(4): 757

60.

PMID

15795430
.

97.

^

Yong Nam Han, Shi Yong Ryu, Byung Hoon Han. Antioxidant activity of resveratrol closely
correlates with its monoamine oxidase
-
A inhibitory activity.

Archives of Pharmacal Research
.
1
990;13(2):132

135.

doi
:
10.1007/BF02857789
.

98.

^

Weber, K; Schulz, B; Ruhnke, M (2011). "Resveratrol and its antifungal activity against
Candida species".

Mycoses

54

(1): 30

3.

doi
:
10.1111/j.1439
-
0507.2009.01763.x
.
PMID

19703269
.

99.

^

Asensi M, Medina I, Ortega A, Carretero J, Baño MC, Obrador E, Estrela JM (August 2002).
"Inhibit
ion of cancer growth by resveratrol is related to its low bioavailability".

Free Radic. Biol.
Med.

33

(3): 387

98.

doi
:
10.1016/S0891
-
5849(02)00911
-
5
.
PMID

1212676
1
.

100.

^

Madhav NV, Shakya AK, Shakya P, Singh K (November 2009). "Orotransmucosal drug
delivery systems: a review".

J Control Release

140

(1): 2

11.

doi
:
10.1016/j.jconrel.2009.07.016
.
PMID

19665039
.

101.

^

a

b

Ansari KA, Vavia PR, Trotta F, Cavalli R (March 2011).
"Cyclodextrin
-
based nanosponges
for deliver
y of resveratrol: in vitro characterisation, stability, cytotoxicity and permeation
study"
.

AAPS PharmSciTech

12

(1): 279

86.
doi
:
10.1208/s12249
-
011
-
9584
-
3
.

PMC

3066340
.
PMID

21240574
.

102.

^

Shojaei AH (
1998). "Buccal mucosa as a route for systemic drug delivery: a review".

J Pharm
Pharm Sci

1

(1): 15

30.
PMID

10942969
.

103.

^

Santos AC, Veiga F, Ribeiro AJ (August 2011).
"New delivery systems to improve the
bioavailability of resveratrol".

Expert Opin Drug Deliv

8

(8): 973

90.
doi
:
10.1517/17425247.2011.581655
.

PMID

21668403
.

104.

^

a

b

c

d

Wal
le T, Hsieh F, DeLegge MH, Oatis JE, Walle UK (December 2004). "High absorption
but very low bioavailability of oral resveratrol in humans".

Drug Metab. Dispos.

32

(12): 1377

82.

doi
:
10.1124/dmd.104.000885
.

PMID

15333514
.

105.

^

ClinicalTrials.gov

NCT00920556

106.

^

la Porte C, Voduc N, Zhang G, Seguin I, Tardiff D, Singhal N, Cameron

DW (July 2010).
"Steady
-
State pharmacokinetics and tolerability of trans
-
resveratrol 2000 mg twice daily with
food, quercetin and alcohol (ethanol) in healthy human subjects".
Clin Pharmacokinet

49

(7):
449

54.

doi
:
10.2165/11531820
-
000000000
-
00000
.

PMID

20528005
.

107.

^

Marier JF, Vachon P, Gritsas A, Zhang J, Moreau JP, Ducharme MP (July 2002). "Metabolism
and di
sposition of resveratrol in rats: extent of absorption, glucuronidation, and enterohepatic
recirculation evidenced by a linked
-
rat model".

J. Pharmacol. Exp. Ther.

302

(1): 369

73.
doi
:
10.1124/jpet.102.033340
.

PMID

12065739
.

108.

^

Abd El
-
Mohsen M, Bayele H, Kuhnle G, Gibson G, Debnam E, Kaila Srai S,

Rice
-
Evans C,
Spencer JP (July 2006). "Distribution of [3H]trans
-
resveratrol in rat tissues following oral
administration".

Br. J. Nutr.

96

(1): 62

70.
doi
:
10.1079/BJN20061810
.

PMID

16869992
.

109.

^

Yu C, Shin YG, Chow A, Li Y, Kosmeder JW, Lee YS, Hirschelman WH, Pezzuto JM, Mehta
RG, van Breemen RB (December 2002). "Human, rat, and mouse metabolism of
resveratrol".

Pharm.
Res.

19

(12): 1907

14.
doi
:
10.1023/A:1021414129280
.

PMID

12523673
.

110.

^

Wang LX, Heredia A, Song H, Zhang Z, Yu B,
Davis C, Redfield R (October 2004).
"Resveratrol glucuronides as the metabolites of resveratrol in humans: characterization,
synthesis, and anti
-
HIV activity".

J Pharm Sci

93

(10): 2448

57.
doi
:
10.1002/jps.20156
.

PMID

15349955
.

111.

^

a

b

c

d

Goldberg DM, Yan J, Soleas GJ (February 2003). "Absorption of three wine
-
r
elated
polyphenols in three different matrices by healthy subjects".

Clin. Biochem.

36

(1): 79

87.
doi
:
10.1016/S0009
-
9120(02)00397
-
1
.

PMID

125540
65
.

112.

^

Wenzel E, Somoza V (May 2005).
"Metabolism and bioavailability of trans
-
resveratrol".

Mol
Nutr Food Res

49

(5): 472

81.

doi
:
10.1002/mnfr.200500010
.

PMID

15779070
.

113.

^

a

b

c

Vitaglione P, Sforza S, Galaverna G, Ghidini C, Caporaso N, Vescovi PP, Fog
liano V,
Marchelli R (May 2005). "Bioavailability of trans
-
resveratrol from red wine in humans".
Mol Nutr
Food Res

49

(5): 495

504.
doi
:
10.1002/mnfr.200500002
.

PMID

15830336
.

114.

^

Corder R, Mullen W, Khan NQ, Marks SC, Wood EG, Carrier MJ, Crozier A (November 2006).
"Oenology: red wine procyanidins and vascular health".

Nature

444

(7119):
566.
doi
:
10.1038/444566a
.

PMID

17136085
.

115.

^

Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge CM (October 2000). "Resveratrol acts as
a
mixed agonist/antagonist for estrogen receptors alpha and beta".

Endocrinology

141

(10): 3657

67.

doi
:
10.1210/en.141.10.3657
.

PMID

11014220
.

116.

^

Levi F, Pasche C, Lucchini F, Ghidoni R, Ferraroni M, La Vecchia C (April 2005).
"Resveratrol
and breast cancer risk".
Eur. J. Cancer Prev.

14

(2): 139

42.

doi
:
10.1097/00008469
-
200504000
-
00009
.

PMID

15785317
.

117.

^

Garvin S, Ollinger K, Dabrosin C (January 2006). "Re
sveratrol induces apoptosis and inhibits
angiogenesis in human breast cancer xenografts in vivo".

Cancer Lett.

231

(1): 113

22.
doi
:
10.1016/j.canlet.2005.01.031
.

PMID

16356836
.

118.

^

a

b

Bråkenhielm E, Cao R, Cao Y (August 2001). "Suppression of angiogenesis,

tumor growth,
and wound healing by resveratrol, a natural compound in red wine and grapes".
FASEB
J.

15

(10): 1798

800.

doi
:
10.1096/fj.01
-
0028fje
.
PMID

11481234
.

119.

^

Leone S, Cornetta T, Basso E, Cozzi R (September 2010). "Resveratrol induces DNA double
-
strand breaks through human topoisomerase II interaction".

Cancer Lett.

295

(2):

167

72.

doi
:
10.1016/j.canlet.2010.02.022
.

PMID

20304553
.

120.

^

Jo JY, Gon
zalez de Mejia E, Lila MA (March 2006).
"Catalytic inhibition of human DNA
topoisomerase II by interactions of grape cell culture polyphenols".

J. Agric. Food Chem.

54

(6):
2083

7.

doi
:
10.1021/jf052700z
.

PMID

16536579
.

121.

^

Paolini M, Sapone A, Valgimigli L (June 2003).
"Avoidance of bioflavonoid
supplements during
pregnancy: a pathway to infant leukemia?".

Mutat. Res.

527

(1

2): 99

101.

doi
:
10.1016/S0027
-
5107(03)00057
-
5
.

PMID

127879
18
.

122.

^

Alcaín FJ, Villalba JM (April 2009). "Sirtuin activators".

Expert Opin Ther Pat

19

(4): 403

14.
doi
:
10.1517/13543770902762893
.

PMID

19441923
.

123.

^

Kaeberlein M, Kirkland KT, Fields S, Kennedy BK (September 2004).

"Sir2
-
independent life
span extension by calorie restriction in yeast"
.

PLoS Biol.

2

(9):
E296.
doi
:
10.1371/journal.pbio.0020296
.

PMC

514491
.
PMID

1532
8540
.

124.

^

a

b

Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA,
Caldwell SD, Napper A,
Curtis R, DiStefano PS, Fields S, Bedalov A, Kennedy BK (April 2005). "Substrate
-
specific
activation of sirtuins by resveratrol".

J. Biol. Chem.

280

(17): 17038

45.

doi
:
10.1074/jbc.M500655200
.

PMID

15684413
.

125.

^

Beher D, Wu J, Cumine S, Kim KW, Lu SC, Atangan L, Wang M (December 2009).
"Resveratrol is not a

direct activator of SIRT1 enzyme activity".

Chem Biol Drug Des

74

(6): 619

24.
doi
:
10.1111/j.1747
-
0285.2009.00901.x
.

PMID

19843076
.

126.

^

Pacholec M, Bleasdale JE, Chrunyk B, Cunningham D, Flynn D, Garofalo RS, Griffith D, Griffor
M, Loulakis P, Pabst B, Qiu X, Stockman B, Thanabal V, Varghese A, Ward J, Withka J, Ahn K
(March 2010).

"SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of
SIRT1"
.

J. Biol. Chem.

285

(11): 8340

51.

doi
:
10.1074/jbc.M109.088682
.

PMC

2832984
.
PMID

20061378
.

127.

^

Robb EL, Page MM, Wiens BE, Stuart JA (March 2008). "Molecular mechanisms of oxidative
stress resistance induced by resveratrol: Specific and progressive induction of

MnSOD".
Biochem. Biophys. Res. Commun.

367

(2): 406

12.
doi
:
10.1016/j.bbrc.2007.12.138
.

PMID

18167310
.

128.

^

Radák, Zsolt (2000).

Free radicals in exercise and aging
. Champaign, IL: Human Kinetics.
p.

39.

ISBN

978
-
0
-
88011
-
881
-
1
.

129.

^

Macmillan
-
Crow LA, Cruthirds DL (April 2001). "Invited review: manganese superoxide
dismutase in disease".

Free Radic. Res.

34

(4): 325

36.

doi
:
10.1080/10715760100300281
.
PMID

11328670
.

130.

^

Cullen JJ, Weydert C, Hinkhouse MM, Ritchie J, Domann FE, Spitz D, Oberley LW (March
2003). "The role of manganese superoxide dismutase in the growth of pancreatic
ad
enocarcinoma".

Cancer Res.

63

(6): 1297

303.
PMID

12649190
.

131.

^

"Mounting evidence shows red wine antioxidant kills cancer"

(Press release).

University of
Rochester Medical Center
. March 26, 2008
. Retrieved August 10, 2010
.

132.

^

Sun J, Folk D, Bradley TJ, Tower J (June 2002).

"Induced overexpression of mitochondrial Mn
-
superoxide dismutase extends the life span of adul
t Drosophila melanogaster"
.
Genetics

161

(2):
661

72.

PMC

1462135
.

PMID

12072463
.

133.

^

Hu D,

Cao P, Thiels E, Chu CT, Wu GY, Oury TD, Klann E (March 2007).

"Hippocampal long
-
term potentiation, memory, and longevity in mice that overexpress mitochondrial superoxide
dismutase"
.

Ne
urobiol Learn Mem

87

(3): 372

84.

doi
:
10.1016/j.nlm.2006.10.003
.

PMC

1847321
.
PMID

17129739
.

134.

^

Wong GH (May 1995). "Protective roles of cytokines against radiation: induction of
mitochondrial
MnSOD".

Biochim. Biophys. Acta

1271

(1): 205

9.

PMID

7599209
.

135.

^

Stefani M, Markus MA, Lin RC, Pinese M, Dawes IW, Morris BJ (October 2007). "The effect of
resveratrol on a cell model of human aging".

Ann. N. Y. Acad. Sci.

1114
: 40
7

18.
doi
:
10.1196/annals.1396.001
.

PMID

17804521
.

136.

^

Brune
t A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky
R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg
ME (March 2004). "Stress
-
dependent regulation of FOXO transcription factors by the
SIRT1
deacetylase".

Science

303
(5666): 2011

5.

doi
:
10.1126/science.1094637
.
PMID

14976264
.

137.

^

Kops
GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL,
Medema RH, Burgering BM (September 2002). "Forkhead transcription factor FOXO3a protects
quiescent cells from oxidative stress".

Nature

419
(6904): 316

21.

doi
:
10.1038/nature01036
.
PMID

12239572
.

138.

^

Leiro J, Arranz JA, Fraiz N, Sanmartín ML, Quezada E, Orallo F (February 2005).
"Effect of cis
-
resveratrol on genes involved in nuclear factor kappa B signaling".

Int. Immunopharmacol.

5

(2):
393

406.

doi
:
10.1016/j.intimp.2004.10.006
.
PMID

15652768
.

139.

^

Chun YJ, Kim MY, Guengerich FP (August 1999). "Resveratrol is a selective human
cytochrome P450
1A1 inhibitor".

Biochem. Biophys. Res. Commun.

262

(1): 20

4.
doi
:
10.1006/bbrc.1999.1152
.

PMID

10448061
.

140.

^

Schwa
rz D, Roots I (April 2003). "In vitro assessment of inhibition by natural polyphenols of
metabolic activation of procarcinogens by human CYP1A1".

Biochem. Biophys. Res.
Commun.

303

(3): 902

7.

doi
:
10.1016/S0006
-
291X(03)00435
-
2
.

PMID

12670496
.

141.

^

a

b

Benitez DA, Pozo
-
Guisado E, Alvarez
-
Barrientos A, Fernandez
-
Salguero PM, Castellón EA
(2007).
"Mechanisms involved in resveratrol
-
induced apoptosis and cell cycle arr
est in prostate
cancer
-
derived cell lines".

J. Androl.

28

(2): 282

93.
doi
:
10.2164/jandrol.106.000968
.

PMID

17050787
.

142.

^

Faber AC, Chiles TC (December 2006).

"Resveratrol induces apoptosis in transformed
follicular lymphoma OCI
-
LY8 cells: evidence for a novel

mechanism involving inhibition of BCL6
signaling"
.

Int. J. Oncol.

29

(6): 1561

6.

PMID

17088997
.

143.

^

Riles WL, Erickson J, Nayyar S, Atten MJ, Attar BM, Holian O (September 2006). "Resveratrol
engages selective apoptotic signals in gastric adenocarcinoma cells".

World
J.
Gastroenterol.

12

(35): 5628

34.

PMID

17007014
.

144.

^

Sareen D, van Ginkel PR, Takach JC, Mohiuddin A, Darjatmoko SR, Albert DM, Polans AS
(September 2006). "Mitochondria as the primary target of resveratrol
-
induced apopt
osis in
human retinoblastoma cells".

Invest. Ophthalmol. Vis. Sci.

47

(9): 3708

16.

doi
:
10.1167/iovs.06
-
0119
.
PMID

16936077
.

145.

^

Tang HY, Shih A, Cao HJ, Davis FB, Davis PJ, Lin HY (August 2006). "Resveratrol
-
induced
cyclooxygenase
-
2 facilitates p53
-
dependent apoptosis in human breast cancer cells".

Mol.
Cancer Ther.

5

(8): 2034

42.

doi
:
10.1158/1535
-
7163.MCT
-
06
-
0216
.

PMID

16928824
.

146.

^

Aziz MH, Nihal M, Fu VX, Jarrard DF, Ahmad N (May 2006). "Res
veratrol
-
caused apoptosis of
human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3'
-
kinase/Akt pathway and Bcl
-
2 family proteins".

Mol. Cancer Ther.

5

(5): 1335

41.

doi
:
10.1158/1535
-
7163.MCT
-
05
-
0526
.
PMID

16731767
.

147.

^

Cao Y, Fu ZD, Wang F, Liu HY, Han R (June 2005).
"Anti
-
angiogenic activity of resveratrol, a
natural compound from medicinal plants".

J Asian Nat Prod Res

7

(3): 205

13.
doi
:
10.1080/10286020410001690190
.

PMID

15621628
.

148.

^

Hung LM, Chen JK, Huang SS, Lee RS, Su MJ (August 2000). "Cardioprotective effect of
resveratrol, a natural antioxidant derived from grapes".

Cardiovasc. Res.

47

(3):

549

55.
doi
:
10.1016/S0008
-
6363(00)00102
-
4
.

PMID

10963727
.

149.

^

Parker JA, Arango M, Abderrahmane S, Lambert

E, Tourette C, Catoire H, Néri C (April 2005).
"Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian
neurons".

Nat. Genet.

37

(4): 349

50.

doi
:
10.1038/ng1534
.
PMID

15793589
.

150.

^

Marambaud P, Zhao H, Davies P (November 2005). "Resveratrol promotes clearance of
Alzheimer's disease amyloid
-
beta peptides".

J. Biol. Chem.

280

(45): 37377

82.
doi
:
10.1074/jbc.M508246200
.

PMID

16162502
.

151.

^

Olson ER, Naugle JE, Zhang X, Bomser JA, Meszaros JG (March 2005). "Inhi
bition of cardiac
fibroblast proliferation and myofibroblast differentiation by resveratrol".

Am. J. Physiol. Heart Circ.
Physiol.

288

(3): H1131

8.
doi
:
10.1152/ajpheart.00763.2004
.

PMID

15498824
.

152.

^

Bhat KP, Lantvit D, Christov K, Mehta RG, Moon RC, Pezzuto JM (October 2001). "Estrogenic
and antiestrogenic properties of resveratrol in mammary tumor models".

Cancer
Res.

61

(20):
7456

63.

PMID

11606380
.

153.

^

Wang Y, Lee KW, Chan FL, Chen S, Leung LK (July 2006). "The red wine polyphenol
resveratrol displays bilevel inhibition on aromatase in breast cancer cells".

Toxicol. Sci.

92

(1):
71

7.
doi
:
10.1093/toxsci/kfj190
.

PMID

16611627
.

154.

^

Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C (March 2004).
"Effects of aromatase
inhibition in elderly men with low or borderline
-
low serum testosterone levels".

J. Clin. Endocrinol.
Metab.

89

(3): 1174

80.

doi
:
10.1210/jc.2003
-
031467
.

PMID

15001605
.

155.

^

Kode A, Rajendrasozhan S, Caito S, Yang SR, Megson IL, Rahman I (March 2008).
"Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against ci
garette
smoke
-
mediated oxidative stress in human lung epithelial cells".

Am. J. Physiol. Lung Cell Mol.
Physiol.

294

(3): L478

88.
doi
:
10.1152/ajplung.00361.2007
.

PMID

18162601
.

156.

^

Ghosh HS, McBurney M, Robbins PD (2010). Blagosklonny, Mikhail V.. ed.

"SIRT1 negatively
regulate
s the mammalian target of rapamycin"
.

PLoS ONE

5

(2):
e9199.
doi
:
10.1371/journal.pone.0009199
.

PMC

2821410
.
PMID

20169165
.

157.

^

Morselli E, Galluzzi L, Kepp O, Criollo A, Maiuri MC, Tavernarakis N,

Madeo F, Kroemer G
(December 2009).
"Autophagy mediates pharmacological lifespan extension by spermidine and
resveratrol"
.

Aging (Albany NY)

1

(12): 961

70.

PMC

2815753
.

PMID

20157579
.

158.

^

Tennen RI, Michishita
-
Kioi E, Chua KF (February 2012). "Finding a target for
resveratrol".

Cell

148

(3): 387

9.
doi
:
10.1016/j.cell.2012.01.032
.

PMID

22304906
.

159.

^

Park
SJ, Ahmad F, Philp A, Baar K, Williams T, Luo H, Ke H, Rehmann H, Taussig R, Brown
AL, Kim MK, Beaven MA, Burgin AB, Manganiello V, Chung JH (February 2012). "Resveratrol
ameliorates aging
-
related metabolic phenotypes by inhibiting cAMP
phosphodiesterases"
.

Cell

148

(3): 421

33.
doi
:
10.1016/j.cell.2012.01.017
.

PMID

22304913
.

160.

^

a

b

c

d

Mattivi F,
Reniero F, Korhammer S (1995). "Isolation, characterization, and evolution in
red wine vinification of resveratrol monomers".

J Agric Food Chem.

43

(7): 1820

3.
doi
:
10.1021/jf00055a013
.

161.

^

Lamuela
-
Raventos RM, Romero
-
Perez AI, Waterhouse AL, de la Torre
-
Boronat MC (1995).
"Direct
HPLC Analysis of cis
-

and trans
-
Resveratrol and Piceid Isomers in Spanish Red Vitis
vinifera Wines".

Journal of Agricultural and Food Chemistry

43
(2): 281

283.

doi
:
10.1021/jf00050a003
.

162.

^

Prokop J, Abrman P, Seligson AL, Sovak M (2006). "Resveratrol and its glycon
piceid are
stable polyphenols".

J Med Food

9

(1): 11

4.

doi
:
10.1089/jmf.2006.9.11
.
PMID

16579722
.

163.

^

Berte
lli AA, Gozzini A, Stradi R, Stella S, Bertelli A (1998). "Stability of resveratrol over time
and in the various stages of grape transformation".

Drugs Exp Clin Res

24

(4): 207

11.
PMID

10051967
.

164.

^

Schroder, Gudrun; Jo
hn W. S. Brown and Joachim Schroder (1988). "Molecular analysis of
resveratrol synthase cDNA, genomic clones and relationship with chalcone synthase".
European
Journal of Biochemistry

172

(1): 161
-
169.

165.

^

Cichewicz, RH; Kouzi, SA; Hamann, MT (2000). "Dimerization of resveratrol by the grapevine
pathogen Botrytis cinerea".
Journal of Natural Products

63

(1): 29

33.

PMID

10650073
.

166.

^

Cichewicz, RH; Kouzi, SA (1998).
"Biotransformation of resveratrol to piceid by Bacillus
cereus".

Journal of Natural Products

61

(10): 1313

4.

doi
:
10.1021/np980139b
.
PMID

9784180
.

167.

^

"The role of grape polyphenols on trans
-
resveratrol activity against Botrytis cinerea and of
fungal laccase on
the solubility of putative grape PR proteins, F. Favaron, M. Lucchetta, S.
Odorizzi, A.T. Pais da Cunha and L. Sella, Journal of Plant Pathology (2009), 91 (3), 579

588,
2009 579"

(PDF)
. Retrieved 2011
-
01
-
22
.

168.

^

Gatto P, Vrhovsek U, Muth J, Segala C, Romualdi C, Fontana P, Pruefer D, Stefanini M, Moser
C, Mattivi F, Velasco R (December 2008). "Ripening and genotype control stilbene accumulation
in healthy grapes".

J. Ag
ric. Food Chem.

56

(24): 11773

85.

doi
:
10.1021/jf8017707
.

PMID

19032022
.

169.

^

a

b

c

d

e

Roy, H., Lundy, S.,

Resveratrol
, Pennington Nutrition Series, 2005 No. 7

170.

^

a

b

c

d

e

LeBlanc, Mark Rene (13 December 2005).

"Cultivar, Juice Extraction, Ultra Violet
Irradiation and Storage Influence the Stilbene Content of Muscadine Grapes (Vitis Rotundifolia
Michx.)"
. Retrieved 2007
-
08
-
15
.

171.

^

Gu X, Creasy L, Kester A, Zeece M (August 1999). "Capillary electrophoretic determination of
resveratrol in wines".

J. Agric. Food Chem.

47

(8): 3223

7.

doi
:
10.1021/jf981211e
.
PMID

10552635
.

172.

^

Mattivi F (June 1993). "Solid phase extraction of trans
-
resveratrol from wines for
HPLC
analysis".

Z Lebensm Unters Forsch

196

(6): 522

5.

doi
:
10.1007/BF01201331
.
PMID

8328217
.

173.

^

Ector BJ, Magee JB, Hegwood CP,
Coign MJ.,

Resveratrol Concentration in Muscadine
Berries, Juice, Pomace, Purees, Seeds, and Wines.

174.

^

Pastrana
-
Bonilla E, Akoh CC, Sellappan S, Krewer G (August 2003). "Phenolic content and
antioxidant capacity of muscadine grapes".

J. Agric. Food Chem.

51

(18): 5497

503.
doi
:
10.1021/jf030113c
.

PMID

12926904
. "Contrary to previous results, ellagic acid and not
resveratrol was the major phenolic in muscadine grapes. The HPLC solvent system used
coupled with fluorescence detection a
llowed separation of ellagic acid from resveratrol and
detection of resveratrol." "[T]rans
-
resveratrol had the lowest concentrations of the detected
phenolics, ranging from not detected in two varieties to 0.2 mg/ 100 g of FW (Tables 1 and 2).
Our result f
or resveratrol differed from previous results [Ector et al., 1996] indicating high
concentrations. These researchers apparently were not able to separate ellagic acid from
resveratrol with UV detection alone."

175.

^

Hudson TS, Hartle DK, Hursting SD, Nunez NP, Wang TT, Young HA, Arany P, Green JE
(September 2007). "Inhibition of prostate cancer growth by muscadine grape skin extract and
resveratrol through distinct mechani
sms".

Cancer Res.

67

(17): 8396

405.

doi
:
10.1158/0008
-
5472.CAN
-
06
-
4069
.
PMID

17804756
. "MSKE [muscadine grape skin extract] does not contain
significant quantities of resveratrol and d
iffers from MSEE. To determine whether MSKE contains
significant levels of resveratrol and to compare the chemical content of MSKE (skin) with MSEE
(seed), HPLC analyses were done. As depicted in Supplementary Fig. S1A and B, MSKE does
not contain signific
ant amounts of resveratrol (<1

?g/g by limit of detection)."

176.

^

Wang KH, Lai YH, Chang JC, Ko TF, Shyu SL, Chiou RY (January 2005). "Germination of
peanut kernels to e
nhance resveratrol biosynthesis and prepare sprouts as a functional
vegetable".

J. Agric. Food Chem.

53

(2): 242

6.
doi
:
10.1021/jf048804b
.

PMID

15656656
.

177.

^

Stewart JR, Artime MC, O'Brian CA (July 2003). "Resveratrol: a candidate nutritional
substance for prostate cancer prevention".
J. Nutr.

133

(7 Suppl): 2440S

2443S.

PMID

12840221
.

178.

^

a

b

Hurst WJ, Glinski JA, Miller KB, Apgar J, Davey MH, Stuart DA (September 2008). "Survey
of the trans
-
resveratrol and trans
-
piceid content of cocoa
-
containing and chocola
te products".

J.
Agric. Food Chem.

56

(18): 8374

8.
doi
:
10.1021/jf801297w
.

PMID

18759443
.

179.

^

"Resveratrol sources"
. Zalet (a site that specializes in Resveratrol information). August 4, 2009
.
Retrieved October 26, 2011
.

180.

^

Mozzon M (1996).

"Resveratrol content in some Tuscan wines"
.

Ital. J. Food Sci.

(Chiriotti,
Pinerolo, ITALIE)

8

(2): 145

52
. Retrieved 2007
-
06
-
18
.

181.

^

a

b

Stervbo U, Vang O, Bonnesen C (2007).
"A review of the content of the putati
ve
chemopreventive phytoalexin resveratrol in red wine".

Food Chemistry

101

(2): 449

57.
doi
:
10.1016/j.foodchem.2006.01.047
.

182.

^

Higdon, Jane; Drake, Victoria J.; Steward, William P. (May 2008).

"Resveratrol"
.

Micronutrient
Information Center
. Linus Pauling Institute.

183.

^

<Please add first missing

authors to populate metadata.> (1999).

"Resveratrol In
Peanuts"
.

Kids Food for Thought

(The Peanut Institute)

1

(4). Archived from

the original

on
August 24, 2000.
[
unreliable source?
]

184.

^

Wang Y, Catana F, Yang Y, Roderick R, van Breemen RB (January 2002). "An LC
-
MS method
for analyzing total resveratrol in grape juice, cranberry juice, and in wine".

J. Agric. Food
Chem.

50

(3): 431

5.

doi
:
10.1021/jf010812u
.
PMID

11804508
.

185.

^

Lyons MM, Yu C, Toma RB, Cho SY, Reiboldt W, Lee J, van Breemen RB
(September 2003).
"Resveratrol in raw and baked blueberries and bilberries".

J. Agric. Food Chem.

51

(20): 5867

70.

doi
:
10.1021/jf034150f
.

PMID

13129286
.

186.

^

Rimas A (2006
-
12
-
11).

"His research targets the aging pr
ocess"
.

The Boston Globe
.

187.

^

Stipp D (2007
-
01
-
19).

"Can red wine help you live forever?"
.
Fortune magazine
.

188.

^

a

b

Seward ZM (2006
-
11
-
30).

"Quest for youth drives craze for 'wine' pills"
. The Wall Street
Journal.

189.

^

"Caution urged with resveratrol"
. United Press International. November 30, 2006
-
11
-
30.

190.

^

Aleccia J (2008
-
04
-
22).

"Longevity quest moves slowly from lab to life"
.

MSNBC
.

191.

^

Gocze T (2008
-
09
-
08).

"Japanese Knotweed a Resilient Invader"
.

Bangor Daily News
.

192.

^

Weintraub A (2009
-
07
-
29).

"Resveratrol: The Hard Sell on Anti
-
Aging"
. Bloo
mberg
Businessweek.

193.

^

Biotransformation of mulberroside A from Morus alba results in enhancement of tyrosinase
inhibition. Jeong
-
Keun Kim, Mijin Kim, Ssang
-
Goo Cho, Myung
-
Kyoo Kim,
Suhng Kim and
Young
-
Hee Lim, Journal of Industrial Microbiology & Biotechnology, Jun 2010, Vol. 37, Issue 6,
page 631,

PubMed

194.

^

Antibacterial phenolics from Boswellia dalzielii. Alemika Taiwo E, Onawunmi Grace O and
Olugbade Tiwalade O, Nigerian Journal of Natural Products and Medicines, 2006 (
abstract
)

External links



Félicien Breton (2008).

"Resveratrol and polyphenols in wines"
.



CTD's Resveratrol page

from the

Comparative Toxicogenomics Database



U.S. National Library of Medicine: Drug Information Portal


Resveratrol



Detailed Micro
-
Nu
trient information on Resveratrol

from the

Linus Pauling Institute



Resveratrol: Don't Buy the Hype



Stay young on red wine drugs?
Think again



Zalet


a site that specializes in Res
veratrol information