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Supreme
antioxidant Resveratrol + grape seed & red wine.
Resveratrol, a natural component of Vitis vinifera L. (Vitaceae),
is abundant in
the skin of grapes and in the leaf epidermis and present in
wines, especially
red wines. It is a polyphenol found in the skin and seeds of
grapes, berries,
peanuts and other foods.
In in vitro, ex vivo and in vivo experiments, resveratrol
exhibits a number of
biological activities, including anti-inflammatory, antioxidant,
platelet antiaggregatory
and anti-carcinogenic properties, and modulation of lipoprotein
metabolism. Some of these activities have been implicated in the
cardiovascular protective effects attributed to resveratrol and
to red wine.
Prior to 2002, there had been no previous studies describing the
potential
effects of resveratrol on the lifespan extension. However, in
the last 5 years,
several researchers have reported that resveratrol is a potent
activator of
sirtuin enzymatic activity, mimics the beneficial effects of
caloric restriction,
retards the aging process and increases longevity in a number of
organisms
from different phyla such as yeasts, worms, flies and
short-lived fish.
In addition, resveratrol seems to be effective in delaying the
onset of a variety
of age-related diseases in mammals, such as rodents. Therefore,
it is possible
that resveratrol may play a role in extending life duration and
on some of the
mechanisms by which resveratrol may act as an anti-aging agent.
Resveratrol in high doses has been shown to extend lifespan in
some studies
in invertebrates and to prevent early mortality in mice fed a
high-fat diet. In a
study, US researchers examined the effect of low dose of dietary
resveratrol
and a calorie restricted (CR) diet on the lifespan of mice. They
fed mice from
middle age (14-months) to old age (30-months) either a control
diet, a low
dose of resveratrol, or a CR diet and examined genome-wide
transcriptional
profiles.
The researchers reported a striking transcriptional overlap of
CR and
resveratrol in heart, skeletal muscle and brain. Both dietary
interventions
inhibited gene expression profiles associated with cardiac and
skeletal muscle
aging, and prevented age-related cardiac dysfunction. Dietary
resveratrol also
mimicked the effects of CR in insulin mediated glucose uptake in
muscle.
Gene expression profiling suggested that both CR and resveratrol
might
retard some aspects of aging through alterations in chromatin
structure and
transcription. Resveratrol, at doses that could be readily
achieved in humans,
was demonstrated to fulfil the definition of a dietary compound
that mimicked
some aspects of CR and retarded some aging parameters.
Resveratrol also possesses chemopreventive and chemotherapeutic
properties and has been shown to increase lifespan in yeast and
metazoans,
including mice. Genetic evidence and in vitro enzymatic
measurements
indicate that the deacetylase Sir2/SIRT1, an enzyme promoting
stress
resistance and aging, is the target of resveratrol. Similarly,
down-regulation of
insulin-like pathways, of which PI3K (phosphoinositide 3-kinase)
is a key
mediator, promotes longevity and is an attractive strategy to
fight cancer.
In France, Fröjdö S. et al showed that resveratrol inhibited, in
vitro and in
cultured muscle cell lines, class IA PI3K and its downstream
signalling at the
same concentration range at which it activated sirtuins. The
observations
defined class IA PI3K as a target of resveratrol that might
contribute to the
longevity-promoting and anticancer properties, and identified
resveratrol as a
natural class-specific PI3K inhibitor.
In the 1997 study reported in the journal Science, resveratrol
was found to
exhibit major inhibitory activity against cancer initiation,
promotion and
progression. Specifically, its antioxidant and anti-mutagenic
potency and
induction of phase II drug-metabolizing enzymes were seen as
counter to
carcinogenic initiation.
Resveratrol hindered cyclooxygenase and hydroperoxidase and
initiated antiinflammatory
effects, thereby demonstrating anti-promotion activity. The
induction of human promyelocytic leukemia cell differentiation
by resveratrol
also thwarted the progress of carcinogenic activity. In
addition, resveratrol
demonstrated significant inhibitory effects in vitro with
carcinogen-induced
preneoplastic lesions in mouse mammary glands, and in vivo with
tumorigenesis in the two-stage mouse skin cancer model. The data
suggest
that resveratrol, a common constituent of the human diet, may be
used as a
potential cancer chemopreventive agent in humans.
Because of lack of early diagnosis and poor therapeutic
responsiveness,
median survival in patients with pancreatic cancer is less than
6 months, and
survival beyond 5 years is rare. Thus, a novel dimension in
chemotherapeutic
agents for pancreatic cancer would be beneficial to control this
metastatic
disease. The effect of resveratrol in pancreatic cancer was
investigated at
Northwestern University Medical School in USA. The potential
role of
resveratrol was evaluated on pancreatic cancer cell
proliferation using two
human pancreatic cancer cell lines, PANC-1 and AsPC-1.
The result showed that resveratrol inhibited proliferation of
both PANC-1 and
AsPC-1. Cell number of both cancer cell lines was also
significantly
decreased following resveratrol treatment. The growth inhibition
induced by
resveratrol was accompanied by apoptotic morphologic changes,
characterized by cell rounding and cell membrane blebbing
suggesting
apoptosis. The substantial apoptosis inducted by resveratrol on
these two cell
lines was confirmed by the terminal deoxynucleotidyl transferase-mediated
deoxyuridine triphosphate nick-end labeling assay.
These findings suggest that resveratrol may have a potent
anti-proliferative
effect on human pancreatic cancer with induction of apoptosis.
Hence
resveratrol is likely to be valuable for the management and
prevention of
human pancreatic cancer.
In a published article in journal Nutrition, Japanese
researchers found that
resveratrol significantly reduced the tumour volume, tumour
weight and
metastasis to the lung in mice bearing highly metastatic Lewis
lung carcinoma
(LLC) tumours. In addition, resveratrol inhibited DNA synthesis
most strongly
in LLC cells, increased apoptosis in LLC cells, and decreased
the S phase
population. Resveratrol inhibited tumour-induced
neovascularization in an in
vivo model. Moreover, resveratrol significantly inhibited the
formation of
capillary-like tube formation from human umbilical vein
endothelial cells
(HUVEC), and the binding of vascular endothelial growth factor (VEGF)
to
HUVEC.
The researchers suggest that the anti-tumour and anti-metastatic
activities of
resveratrol might be due to the inhibition of DNA synthesis in
LLC cells and
the inhibition of LLC-induced neovascularization and tube
formation
(angiogensis) of HUVEC by resveratrol.
Resveratrol has strong antioxidative properties that have been
associated
with the protective effects of red wine consumption against
coronary heart
disease, which is commonly known as "the French paradox". In a
Korean
study, Jang J.H. and Surh Y.J. investigated the effects of
resveratrol on betaamyloid-
induced oxidative cell death in cultured rat pheochromocytoma
(PC12)
cells. There has been compelling evidence supporting the idea
that betaamyloid-
induced cytotoxicity is mediated through the generation of
reactive
oxygen intermediates (ROIs).
PC12 cells treated with beta-amyloid exhibited increased
accumulation of
intracellular ROI and underwent apoptotic death. Beta-amyloid
treatment also
led to the decreased mitochondrial membrane potential, the
cleavage of
poly(ADP-ribose)polymerase, an increase in the Bax/Bcl-X(L)
ratio, and
activation of c-Jun N-terminal kinase.
Resveratrol was found to attenuate cytotoxicity, apoptosis, and
intracellular
ROI formation. The polyphenol also thwarted other effects of the
beta-amyloid
peptide, which is believed to account for the plaques that are
characteristic of
brain tissue in patients with Alzheimer's disease.
In India, Palsamy P. and Subramanian S. carried out a study to
evaluate the
anti-diabetic properties of resveratrol in
streptozotocin-nicotinamide induced
experimental diabetes in rats. The diabetic rats orally treated
with resveratrol
for 30 days resulted in significant decrease in the levels of
blood glucose,
glycosylated hemoglobin, blood urea, serum uric acid, serum
creatinine and
diminished activities of pathophysiological enzymes such as
aspartate
transaminase, alanine transaminase and alkaline phosphatase.
The anti-hyperglycemic nature of resveratrol is also evidenced
from the
improvement in the levels of plasma insulin and haemoglobin.
Further, the
results are comparable with glyclazide, an oral standard
anti-diabetic drug.
Thus, these findings suggest that resveratrol may be considered
as an
effective therapeutic agent for the treatment of diabetes
mellitus.
Many studies have shown that resveratrol has anti-inflammatory
properties,
and it has been ascribed as having health benefits that help to
prevent cancer
and coronary heart disease. A treatment that combines
anti-microbial and
anti-inflammatory actions may be desirable for alleviating many
skin
conditions that range in severity.
Chan M.M., from Department of Microbiology and Immunology at
Temple
University School of Medicine in Philadelphia, evaluated the
anti-microbial
activity of resveratrol against bacteria and dermatophytes that
are major
etiologic agents of human skin infections. Resveratrol inhibited
the growth of
the bacterial species Staphylococcus aureus, Enterococcus
faecalis, and
Pseudomonas aeruginosa, and the activity against the fungal
species
Trichophyton mentagrophytes, Trichophyton tonsurans,
Trichophyton rubrum,
Epidermophyton floccosum, and Microsporum gypseum.
Thus, this study indicates a novel application for resveratrol,
a molecule of
plant defense, to combat human fungal pathogens. Resveratrol may
have
wide application to skin conditions and may also have promising
clinical
potentials in diabetic wounds.
In summary, resveratrol, a naturally occurring antioxidant
primarily found in
red wine and grapes, exhibits a number of biological activities
in human body.
These include anti-inflammatory, antioxidant, anti-tumour,
anti-hyperglycemic,
anti-microbial, and anti-carcinogenic properties. Resveratrol
may also mimic
the effects of calorie restriction and retard the aspects of
aging.
Together with grape seed and red wine, resveratrol is a potent
antioxidant
boost, which helps to protect the body against free radical
damage that is
normally associated with premature aging and disease. It also
supports a
healthy cardiovascular and immune system for optimal wellness.
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