cis- Resveratrol and trans- Resveratrol
Antiplatelet activity of cis-resveratrol.
Institute of Anatomy, University of Milan, Italy.
The anti-aggregating effect of cis-resveratrol (cis-3,4,5- trihydroxystilbene) has been evaluated in vitro in different concentrations on platelet-rich plasma from health volunteers. Cis-resveratrol at the concentration of 1 x 10(-5) and 1 x 10(-6) M was able to decrease collagen-induced platelet aggregation by 43.5 +/-11.4% and 26.8 +/- 14.6%, while trans-resveratrol at the same concentration showed a slightly lower activity. In view of the behaviour of these two isomers in biological fluids, the evaluation of resveratrol activity in animals and humans take into account the total amount of the two isomers.
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Resveratrol Isolated from Japanese Knotweed Extract (Polygonum cuspidatum) Root Prevents Tumor Growth and Metastasis to Lung and Tumor-Induced
Neovascularization in Lewis Lung Carcinoma-Bearing Mice
Yoshiyuki Kimura1 and Hiromichi Okuda
Second Department of Medical Biochemistry, School of Medicine, Ehime University, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan
Resveratrol is a naturally occurring phytoalexine found in medicinal plants. We found that resveratrol, at doses of 2.5 and 10 mg/kg, significantly reduced the tumor volume (42%), tumor weight (44%) and metastasis to the lung (56%) in mice bearing highly metastatic Lewis lung carcinoma (LLC) tumors, but not at a dose of 0.6 mg/kg. Resveratrol did not affect the number of CD4+, CD8+ and natural killer (NK)1.1.+ T cells in the spleen. Therefore, the inhibitory effects of resveratrol on tumor growth and lung metastasis could not be explained by natural killer or cytotoxic T-lymphocyte activation. In addition, resveratrol inhibited DNA synthesis most strongly in LLC cells; its 50% inhibitory concentration (IC50) was 6.8 Âµmol/L. Resveratrol at 100 Âµmol/L increased apoptosis to 20.6 Â± 1.35% from 12.1 Â± 0.36% (P < 0.05) in LLC cells, and decreased the S phase population to 22.1 Â± 1.03% and 29.2 Â± 0.27% from 35.2 Â± 1.72% (P < 0.05) at concentrations of 50 and 100 Âµmol/L, respectively. Resveratrol inhibited tumor-induced neovascularization at doses of 2.5 and 10 mg/kg in an in vivo model. Moreover, resveratrol significantly inhibited the formation of capillary-like tube formation from human umbilical vein endothelial cells (HUVEC) at concentrations of 10-100 Âµmol/L; the degree of the inhibition of capillary-like tube formation by resveratrol was 45.5% at 10 Âµmol/L, 50.2% at 50 Âµmol/L and 52.6% at 100 Âµmol/L. Resveratrol inhibited the binding of vascular endothelial growth factor (VEGF) to HUVEC at concentrations of 10-100 Âµmol/L, but not at concentrations of 1 and 5 Âµmol/L. The degree of inhibition of VEGF binding to HUVEC by resveratrol was 16.9% at 10 Âµmol/L, 53.2% at 50 Âµmol/L and 47.8% at 100 Âµmol/L. We suggest that the antitumor and antimetastatic 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.
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Resveratrol may help you lose weight
Study also shows resveratrol may promote longer life
THE WASHINGTON POST
A substance found in grape skins and Japanese Knotweed (polygonum cuspidatum) protected mice from the ill effects of obesity, raising the tantalizing prospects the compound could do the same for humans and may also help people live longer, healthier lives, researchers reported.
The substance, called resveratrol, enabled mice that were fed a high-calorie, high-fat diet to live normal, active lives despite becoming obese - the first time any compound has been shown to do that. Tests found the agent activated a host of genes that protect against the effects of aging, essentially neutralizing the adverse effects of a bad diet on the animals’ health and lifespan.
Although much more work is needed to explore the benefits and safety of the substance, which is sold over the counter as a nutritional supplement, the findings could lead to the long-sought goal of extending the healthy human lifespan, experts said. Preliminary tests in people are already underway.
"We’ve been looking for something like this for the last 100,000 years, and maybe it’s right around the corner - a molecule that could be taken in a single pill to delay the diseases of aging and keep you healthier as you grow old," said David A. Sinclair, a Harvard University molecular biologist who led the study. "The potential impact would be huge."
The findings triggered excitement among scientists studying aging, who hailed the findings as groundbreaking. "This represents a likely major landmark," said Stephen Helfand, who studies the molecular genetics of aging at Brown University. "This really pushes the field forward. It’s quite exciting."
The research, being published in today’s issue of the journal Nature, helps explain a host of observations that have long intrigued researchers, including why French people tend to get fewer heart attacks and why severely restricting the amount of calories animals ingest makes them live longer.
"This gives us hope that the idea of harnessing the power of calorie restriction is not a fantasy and can be brought to reality," said Leonard Guarente, who studies the biology of aging at the Massachusetts Institute of Technology. "This could produce a whole new approach to preventing and treating the diseases of aging." Previous research has shown that laboratory animals fed very low-calorie diets live significantly longer, which has prompted some people to strenuous "caloric restriction" diets as a possible fountain of youth, even though its effectiveness in humans remains unproven.
In the hope of finding a drug that could harness the natural life-extending capabilities activated by caloric restriction, Sinclair and his colleagues identified a number of the promising compounds, including resveratrol. Resveratrol, which increases the activity of enzymes known as sirtuins, prolonged the lifespan of every organism scientists have tested it on, including yeast, worms, fish and fruit flies.
The researchers cautioned that the findings should not encourage people to eat badly, thinking resveratrol could make gluttony completely safe. They also noted that a person would have to drink at least 100 bottles of red wine a day (average of 3 mg per bottle) or take mega doses of the commercially available supplements to get the levels given to the mice.
But the findings indicate that resveratrol or molecules like it could have myriad benefits, and several aging researchers said the results tempted them to start using the supplements in the meantime.
"I’m usually a very cautious person," said Cynthia Kenyon of the University of California in San Francisco. "But I’m seriously thinking about taking resveratrol myself."
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Resveratrol found to counter effects of obesity also aids endurance
NEW YORK TIMES
Resveratrol, already shown to reverse the effects of obesity in mice and make them live longer has now been shown to increase their endurance, as well.
Experts say the finding may open a new field of research on similar substances that may be relevant to the prevention of diabetes and other diseases. An ordinary lab mouse will run 1 kilometer on a treadmill before collapsing from exhaustion. But mice given resveratrol, a component of Japanese Knotweed (polygonum cuspidatum), and red wine, run twice as far. They also have a reduced heart rate and energy-charged muscles, just as trained athletes do according to an article published by Johan Auwerx and colleagues at the Institute of Genetics and Molecular and Cellular Biology in Illkirch, France.
He and his colleagues said the same mechanism seems likely to operate in humans, based on their analysis of a group of Finnish subjects of the gene that is influenced by resveratrol.
Their rationale for testing resveratrol was evidence obtained three years ago that it could trigger a genetic mechanism known to protect mice against the degenerative diseases of aging and prolong their lifespan.
Auwerx, whose interest is in the genetic control of metabolism, decided to see if resveratrol would offset the effects of a high-fat diet. In his report, he and his colleagues say very large doses of resveratrol protected mice from gaining weight and developing metabolic syndrome.
Auwerx attributes this chance in large part to the significantly increased number of mitochondria he detected in the muscle cells of treated mice.
Mitochondria are the organelles within the body’s cells that generate energy. With extra mitochondria, the treated mice were able to burn off more fat and thus avoid weight gain and decreased sensitivity to insulin, Auwerx said.
Ronald M. Evans, a leading expert on the hormonal control of metabolism at the Salk Institute, said the report by Auwerx’s team had "shown very convincingly that resveratrol improves mitochondrial function" and fends off metabolic disease. He described the study as "very important, because it is rare that we identify orally active molecules, especially natural molecules, that have such a broad-based, positive effect on a problem which is as wide spread in society as metabolic disease."
Auwerx’s study compliments one published earlier this month by David Sinclair of the Harvard Medical School, who found that much more moderate doses protected mice from the metabolic effects of a high-calorie diet. Though his mice did not lose weight, they lived far longer than the undosed mice fed the same high-calorie diet.
there," he said.
Edited by pembroke3355, 17 November 2008 - 07:31 PM.