Resveratrol is a substance that is produced by several plants and that is sold as a nutritional supplement. A number of beneficial health effects, such as anti-cancer, anti-viral, neuroprotective, anti-aging, anti-inflammatory and life-prolonging effects have been reported. Resveratrol is found in the skins of red grapes, and as a constituent of red wine it has been implicated in the “French paradox” (that the incidence of coronary heart disease is relatively low in southern France despite high dietary intake of saturated fats). Resveratrol may also be synthesized.
Plants and foods
Resveratrol is produced by plants as an antifungal. It is found in the skins of certain red grapes, in peanuts, blueberries, some pines (Scots pine, eastern white pine) and the roots and stalks of Japanese knotweed (hu zhang in China) and giant knotweed. Resveratrol was first isolated from an extract of the Peruvian legume Cassia quinquangulata in 1974.
The amount of resveratrol in food substances varies greatly. Red wine contains approximately 5 mg/L, depending on the grape variety, whilst white wine has much less - the reason being that red wine is fermented with the skins, allowing the wine to absorb the resveratrol, whereas white wine is fermented after the skin has been removed.
Chemical & physical properties
Resveratrol is a polyphenolic phytoalexin. It is a stilbenoid, a derivate of stilbene, and is produced in plants with the help of the enzyme stilbene synthase.
It exists as two structural isomers: cis- (Z) and trans- (E), with the trans-isomer shown in the image. Trans-resveratrol can undergo isomerisation to the cis form when heated or exposed to UV irradiation.
Supplement
Resveratrol is available as a mass-produced nutritional supplement but not as a therapeutic agent (though it is now registered as an investigational drug). The supplement, first sourced as ground dried red grape skins, has shifted somewhat to include certain of the knotweeds as a raw material.
Resveratrol is often referred to as a nutraceutical, along with other bioactive plant compounds that are being studied for potential clinical applications such as curcumin, EGCG and silibinin, among others.
It appears that resveratrol, cholikan and activin GSE 2000 are the same chemical substance.
Physiological effects
Activities & mechanisms of action
Resveratrol interferes with all three stages of carcinogenesis - initiation, promotion and progression. Experiments in various cell types and isolated subcellular systems in vitro implicate a multitude of mechanisms in the pharmacological activity of resveratrol. These mechanisms include inhibition of the transcription factor NF-kB, cytochrome P450 isoenzyme CYP1A1, androgenic actions and expression and activity of cyclooxygenase (COX) enzymes. Resveratrol has been shown to induce Fas/ Fas ligand mediated apoptosis, p53 and cyclins A, B1 and cyclin-dependent kinases cdk 1 and 2, furthermore it possesses antioxidant and anti-angiogenic properties. Due to these discoveries resveratrol is currently being investigated extensively as a cancer chemopreventive agent.
Resveratrol has recently been reported to be effective against neuronal cell dysfunction and cell death, and may be of use for diseases such as Huntington's disease and Alzheimer's disease.
Recent research at Ohio State University indicated that resveratrol inhibits the development of cardiac fibrosis.
It is worth mentioning that resveratrol bioavailability is dependent on its conjugate forms: glucuronate and sulfonate, despite almost all in vitro studies use the aglycone form of resveratrol. Furthermore, if resveratrol is taken in with food, most of it is destroyed by the digestive system.
Life extension and anti-aging
Experiments from the laboratory of David Sinclair at Harvard were published in 2003 the journal Nature claiming that resveratrol significantly extends the lifespan of the yeast Saccharomyces cerevisiae. [1] Dr. Sinclair then founded Sirtris pharmaceuticals to commericalize resveratrol as an anti-aging drug.
Later studies showed that resveratrol prolongs the lifespan of the worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. In 2006 it was shown that it also extends the maximum lifespan of a short-lived fish, Nothobranchius furzeri, by 59% and the median lifespan by 56%. Also noted were an increase in swimming performance, an increase in cognitive performance (learning tasks), and no neurofibrillary degeneration (which was found in a control group). The authors wrote "the observation that [resveratrol's] supplementation with food extends vertebrate lifespan and delays motor and cognitive age-related decline could be of high relevance for the prevention of aging-related diseases in the human population."[2]
The mechanisms of resveratrol's apparent effects toward life extension are not fully understood. It was believed to have longevity-enhancing properties by acting as a CR-mimetic, but this has since been shown not to be true.
Only the trans-form is capable of activating the mammalian SIRT1 gene in vitro; it is also the form predominantly found in red grape skin (red wine).
Anti-viral effects
Resveratrol has also been seen to increase the potency of some antiretroviral drugs in vitro.
A cell culture study has found that resveratrol thwarts the ability of the influenza virus from carring viral proteins to the viral building site, hence restricting the ability to replicate. The effect was 90% when resveratrol was added six hours after infection and continued for 24 hours thereafter.[3]
In humans resveratrol rapidly undergoes phase II conjugation, both glucuronidation and sulphation at multiple sites on the molecule. The effect of conjugation on efficacy is debated ( see and see).
References
- ↑ Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003 Sep 11;425(6954):191-6. Epub 2003 Aug 24. PMID 12939617
- ↑ Valenzano et al.: "Resveratrol Prolongs Lifespan and Retards the Onset of Age-Related Markers in a Short-Lived Vertebrate." Publishing in Current Biology 16, 296-300, February 7, 2006. PMID 16461283
- ↑ Palamara AT, Nencioini L, Aquilano K, et al. Inhibition of influenza A virus replication by resveratrol. Journal of Infectious Diseases May 2005 15;191(10):1719-29. PMID 15838800
- Gescher AJ, Steward WP. Relationship between mechanisms, bioavailibility, and preclinical chemopreventive efficacy of resveratrol: a conundrum. Cancer Epidemiol Biomarkers Prev. 2003;12(10):953-957.Free full text
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