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.