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Topical resveratrol

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#1 tintinet

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Posted 09 February 2008 - 12:39 AM

Baxter RA.
Anti-aging properties of resveratrol: review and report of a potent new
antioxidant skin care formulation.
J Cosmet Dermatol. 2008 Mar;7(1):2-7.
PMID: 18254804



Resveratrol, an antioxidant polyphenol from red wine, has been the subject
of intense interest in recent years due to a range of unique anti-aging
properties. These include cardiovascular benefits via increased nitric oxide
production, down-regulation of vasoactive peptides, lowered levels of
oxidized low-density lipoprotein, and cyclooxygenase inhibition; possible
benefits on Alzheimer's disease by breakdown of beta-amyloid and direct
effects on neural tissues; phytohormonal actions; anticancer properties via
modulation of signal transduction, which translates into anti-initiation,
antipromotion, and antiprogression effects; antimicrobial effects; and
sirtuin activation, which is believed to be involved in the caloric
restriction-longevity effect.

Here we report a resveratrol-based skin care formulation, with 17 times
greater antioxidant activity than idebenone. The role of resveratrol in
prevention of photoaging is reviewed and compared with other antioxidants
used in skin care products.


The ideal anti-aging intervention should be applicable for both cosmetic
maintenance of an age-appropriate healthful appearance, stemming the
development of degenerative diseases, optimizing the function of the aging
brain and other tissues, and acting on biologic systems known to prolong
lifespan. Although there is continuing debate about defining anti-aging, and
whether there is indeed any true anti-aging intervention, 1,2 there is more
of a consensus about what factors contribute to biologic aging. The
oxidative theory 3 has gained scientific acceptance and considerable
traction in the public's mind, and antioxidants are a popular ingredient in
dietary and skin care products. Genetic factors play another important but
not overriding role, 4 and modulation of genetic expression is another front
in the anti-aging battle. 5 Caloric restriction remains the only proven
means of lifespan extension in the animal model and is believed to occur via
up-regulation of an evolutionarily conserved class of enzymes known as
sirtuins, 6 involved in mitochondrial metabolism. Reports in recent years
that the caloric restriction effect could be elicited in progressively
complex organisms via sirtuin activation by the polyphenolic phytoalexin
resveratrol 7-9 has generated considerable interest. Resveratrol has been
the subject of intensive investigation in recent years (Fig. 1) and is
reported to be an extremely potent antioxidant, a modulator of genetic
expression via signal transduction, an inhibitor of inflammatory mediators,
and to have other actions including phyto-hormonal effects. This combination
of biological properties and cosmetic effects makes resveratrol a unique
candidate anti-aging agent.

Resveratrol (3,5,4'-trihydroxystilbene) is a naturally occurring molecule
found in high concentrations in many red wines and is a member of a family
of compounds known as wine polyphenols, which also includes flavonoids. 10
Other sources of resveratrol include some colored berries and the nonedible
parts of the peanut plant. Of the two isoforms, the trans-resveratrol isomer
is more stable and biologically active than the cis-resveratrol isomer. 11
Resveratrol has been reported to be a strong inhibitor of NADPH- and
adenosine 5'-diphosphate (ADP)-Fe+-lipid peroxidation and ultraviolet (UV)
light-induced lipid peroxidation, and an efficient scavenger of
2,2'-azobis-(2-amidinopropane)-dihydrochloride peroxyl radicals. 12 Several
studies have evaluated the structure-activity relationship of resveratrol
and other stilbene derivatives. Olas and Wachowicz 13 evaluated the
activities of resveratrol in platelets and determined that the hydroxyl
group in ring B was important in the inhibition of the production of
reactive oxygen species, reduction of lipid peroxidation, and protection
against peroxynitrate-induced platelet lipid and protein oxidation.
Stojanovic et al. 14 also found resveratrol to be an extremely efficient
free radical scavenger in a model employing gamma-irradiation of liposomes,
with the para-hydroxyl configuration the most effective. Resveratrol was 95%
efficient at preventing lipid peroxidation, compared with ~65% for vitamin E
and ~37% for vitamin C. Flavonoid polyphenols are more ubiquitous.
Silymarin, derived from the milk thistle plant, has been found to share some
properties with resveratrol, including an antiapoptotic effect following UV
radiation, modulation of signal transduction, and sirtuin activation. 15
Topical and systemic administration of silymarin was shown to attenuate
burn-induced oxidative tissue injury in rats 16 and is being evaluated for
chemoprevention of prostate and skin cancers. 17 Direct comparisons of
silymarin's antioxidant capacity with other polyphenols has not been
reported, however, and this compound has not been extensively studied.


The inverse relationship between wine consumption and heart disease ('French
paradox') has been known for some time and well documented. 18-20
Resveratrol and other wine phenolics are believed to be largely responsible
for this correlation via increased nitric oxide production, 21
down-regulation of vasoactive peptides known as endothelins, 22 reduction of
oxidized low-density lipoprotein, 23 and anti-inflammatory effects via
cyclooxygenase (COX) inhibition and down-regulation of eicosanoid synthesis.

Brain function

Population studies reveal a consistent inverse relationship of moderate wine
consumption and Alzheimer's/senile dementia as well as overall better
maintenance of cognitive ability with advancing age. 25 Resveratrol has been
shown to facilitate the breakdown of beta-amyloid, which is associated with
Alzheimer's disease, via specific mechanisms unrelated to antioxidant
effects, 26 and to protect against beta-amyloid toxicity in vitro. 27
Mitogen-activated protein enzymes (MAP kinases), which are active in
learning and memory centers of the brain, are up-regulated by resveratrol in
neural tissues. 28 Neuronal AMP kinases are also activated by resveratrol.

Resveratrol has also been shown to protect the brain against the effects of
traumatic injury in a rat model. 30 In a gerbil stroke model, resveratrol
administered either during or after carotid artery occlusion significantly
decreased cerebral ischemic injury. 31 This same study documented the
ability of resveratrol to traverse the blood-brain barrier.

Phyto-hormonal effects

Resveratrol is known to bind the estrogen receptor, 32 and evidence suggests
that regular wine consumption attenuates perimenopausal symptoms 33 and
protects against osteoporosis. A report from China Medical University in
Taiwan 34 concluded that resveratrol's bone-protective effects were similar
to hormone replacement therapy (HRT), without increased risk of breast
cancer, via signal-transduction mediated effects resulting in activation of
forkhead proteins, which were also involved in anticancer effects. Given
current controversies about HRT following the Women's Health Initiative
report, 35 this may prove extremely valuable, but remains to be clinically
documented in prospective trials.

Phytoestrogens are being investigated as possible selective cytoplasmic and
membrane surface estrogen receptor agonists to slow skin aging without the
potential risks of estrogen. 36 Estrogen is known to enhance dermal
water-holding capacity, increase glycosaminoglycan content, maintain skin
elasticity and collagen content, and diminish wrinkling, although specific
data on stilbene phytestrogens such as resveratrol are lacking. 37


Wine polyphenols as a class are the most potent dietary antioxidants,
generally many times greater than vitamins A, C, and E. Large trials of
vitamin supplementation have consistently found no reduction in the
incidence of degenerative diseases. 38-40 Dietary intervention studies have
documented a reduction of serum oxidative damage markers to a greater degree
with the addition of red wine compared with vegetables rich in antioxidant
vitamins. A representative study from the Catholic University of Chile in
Santiago compared total plasma antioxidant capacity, levels of leukocyte DNA
8-OHdeoxyguanosine (8OHdG, a marker for DNA oxidation), and plasma
7C-hydroxycholesterol, in groups of volunteers given an occidental
(high-fat) diet, a Mediterranean diet, or a Mediterranean diet supplemented
isocalorically with either red wine or additional fruits and vegetables, for
3 months. 41 The wine-supplemented diet was more than twice as effective at
reducing serum markers of oxidative stress than the vegetable added diet. A
consensus is emerging that polyphenols, rather than antioxidant vitamins
alone, are responsible for the anti-aging benefits of the Mediterranean

Polyphenols from tea, primarily catechins and theaflavins, are also known to
be potent antioxidants, although comparison data are sparse. A few in vivo
studies document direct antioxidant activity through free radical scavenging
and chelation of redox-active transition metal ions, and indirect actions
including induction of the phase II antioxidant enzymes superoxide
dismutases and glutathione S-transferases. 42 Photoprotection has also been
seen with topical application or oral ingestion of the tea polyphenol
(-)-epigallocatechin-3-gallate, with inhibition of carcinogen chemical- or
UV radiation-induced skin carcinogenesis in various in vivo models. 43
Catechins, epicatechins, and gallic acids also occur in substantial amounts
in red wine, along with ellagic acid, the primary antioxidant polyphenol in
pomegranates. Peroxyl radical scavenging activities of these various
compounds have been compared, with results in decreasing order found to be
resveratrol > catechin > epicatechin = gallocatechin > gallic acid = ellagic
acid. 44

The synthetic coenzyme Q analog idebenone has been reported to be the
strongest topical antioxidant. 45 Although all antioxidants ultimately
function by scavenging reactive oxygen species, a variety of tests are
employed including direct chemical measurements of free radical
neutralization and biological in vitro and in vivo assays. A new product
with 1% resveratrol (FAMAR, Athens, Greece) developed for Calidora Skin
Clinics (Seattle, WA) was tested against 1% idebenone (Prevage MD, Allergan,
Inc., Irvine, CA) using the ORAC test (Oxygen Radical Absorbance Capacity,
Brunswick Laboratories, Norton, MA), an industry standard for cosmetics and
nutrition. The resveratrol product yielded 4845 µmole VE/g (vitamin E
equivalent per gram) compared with 279 for the 1% idebenone, approximately a
17-fold increase in antioxidant potency. Clinical testing is underway for
this promising formulation.

Go to sectionTop of pageAbstractIntroductionCardiovascularBrain
functionPhyto-hormonal effectsAntioxidantPrevention of
photoagingAnticancerInfectious diseasesResveratrol as a sirtuin
mimet...Outlook for clinical useReferences
Prevention of photoaging

Botanical antioxidant compounds as a key ingredient in skin care products
have received recent attention and validation of efficacy. The use of
resveratrol and other botanical antioxidants has been reviewed by Afaq and
Mukhtar 46 and Baliga and Katiyar. 47 Resveratrol has been demonstrated to
act on cellular signaling mechanisms related to UV-mediated photoaging,
including MAP kinases, nuclear factor kappa B (NF-kappa-B), and matrix
metalloproteinases. Topical application of resveratrol in a SKH-1 hairless
mouse model prior to UV-B radiation results in significant inhibition of
cellular proliferation, mRNA survivin expression, and survivin
phosphorylation. Resveratrol lowers levels of reactive oxygen species in
UVA-exposed HaCaT keratinocytes in a dose-dependent manner, and electron
microscopy confirmed that ultrastructural changes could be prevented. 48


Several lines of evidence point to a role for resveratrol and other wine
phenolics in chemoprevention of cancer as well as possible therapeutic
roles. 49,50 Mechanisms at each step in carcinogenesis have been mapped in
detail, with resveratrol acting as an anti-initiation, antipromotion, and
antiprogression agent. 51 At the initiation level, antioxidant capabilities
are believed to be important, whereas induction of apoptosis, decreased
expression of antiapoptotic proteins, and down-regulation of cell activation
pathways are involved in antipromotion effects. Antiprogression actions
include suppression of growth factor signaling pathways, suppression of
cancer cell growth, and inhibition of angiogenesis. 52 Direct suppression of
breast cancer cells, 53 melanoma, 54 and many others by resveratrol has been
reported. These effects are mediated through up-regulation of p12Cip1/WAF1,
p53, and Bax; down-regulation of survivin, cyclin E, Bcl-2, Bcl-xL, and
clAPS; activation of caspases; and suppression of transcription factors
including NF-kappa-B, AP-1, and Egr-1, and JAK-STAT. 55 Inhibition of
several protein kinases and COX-2 is also believed to be important.

Resveratrol has also been demonstrated to enhance the effectiveness of
cisplatin and doxorubicin in human ovarian (OVCAR-3) and uterine (Ishikawa)
cancer cell lines, attenuating the cardiotoxic effects in rodent ventricular
myocytes. 56 Resveratrol and other wine polyphenols act as chemosensitizers
and radiosensitizers by blocking pathways that lead to treatment resistance.

Infectious diseases

Resveratrol is produced in the skin of wine grapes in response to
environmental stress, and is known to have antifungal, antibacterial, and
antiviral properties. 58 Influenza virus replication has been shown to be
inhibited by resveratrol 59 via blockade of the nuclear-cytoplasmic
translocation of viral proteins, most likely related to protein kinase C
activity, and mice infected with the influenza virus showed significantly
better survival when treated with resveratrol. Antimicrobial effects on
dermatophytes and bacterial pathogens of the skin have also been documented.

Resveratrol as a sirtuin mimetic

Caloric restriction promotes longevity through activation of histone
deacetylase enzymes known as sirtuins, 6 a phenomenon documented across
animal species from simple organisms to vertebrates. 7,8 It is believed to
be based upon a survival response to nutritional or other environmental
stress, with altered mitochondrial metabolism, increased insulin
sensitivity, lowered levels of insulin-like growth factor-1, increased
AMP-activated protein kinase, and other downstream effects. Wine polyphenols
are the only known sirtuin mimetics capable of replicating the calorie
restriction effect by up-regulating sirtuin activity. The adverse effects of
a high-calorie diet on mice were reversed with resveratrol, 9 and studies in
primates are ongoing. The effects in humans have not yet been reported,
though at least two biotechnology companies are developing resveratrol
formulations for prescription use in diabetes and degenerative diseases.

Outlook for clinical use

Pending reports of prospective clinical trials in humans for specific
conditions, the benefits of oral supplementation of resveratrol remain
speculative. Questions about bioavailability, metabolism, and dosing remain
largely unanswered as yet. Resveratrol seems to be rapidly absorbed after
oral ingestion but quickly conjugated by glucuronic acid, although it may
accumulate in epithelial tissues. 61,62 In pigs, resveratrol has been
demonstrated to absorb well through the stratum corneum though not as well
as a phosphorylated conjugate. 63 Topical use therefore seems to pose little
theoretical risk and potentially large benefits. Synthetic resveratrol
derivatives may allow for more targeted applications, although the native
form is many times more potent in free radical absorption capacity than
antioxidant vitamins and derivatives currently in use.

#2 Eva Victoria

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Posted 24 February 2008 - 01:13 PM

The University of Massachusetts has stabilized resveratrol molecule which is being used in a patented form (Resveratrate™) by Estee Lauder Renutriv Ultimate youth Creme ($ 250).


Edited by Eva Victoria, 24 February 2008 - 01:14 PM.

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#3 edward

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Posted 24 February 2008 - 05:09 PM

The University of Massachusetts has stabilized resveratrol molecule which is being used in a patented form (Resveratrate™) by Estee Lauder Renutriv Ultimate youth Creme ($ 250).


That flash marketing video along with the $250 price tag for 1.7 oz of the stuff makes me gag. Think about the profit margins. Now we know that Resveratrol is stable without any special proccessing so there is really no need for their "Resveratrate", and they don't even tell you how much of the stuff is in their 1.7 oz cream. I think my $5 aveno cream spiked with 99% t-res that has lasted months is probably more potent then their 1.7 oz $250 stuff.

#4 edward

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Posted 24 February 2008 - 05:21 PM

Posted Image

umm I don't think so

Now I am the first to admit that I know very little about skin care from an external topical perspective. But I do have a grasp of pharmacology, supplementation, nutrition and for that matter marketing, and something here doesn't add up to $250 per 1.7 oz

#5 Eva Victoria

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Posted 24 February 2008 - 07:47 PM

I have to agree with you on this one. Nothing can justify $250 for "hope in a jar".

#6 missminni

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Posted 24 February 2008 - 11:39 PM

I have to agree with you on this one. Nothing can justify $250 for "hope in a jar".

Sounds like they are going to compete with La Mer.
I've mixed res with lots of different face creams. It blends really well.
Does anyone have a favorite cream they mix it with that they are seeing results from?

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