Resveratrol

from Wikipedia, the free encyclopedia
Structural formula
Resveratrol structural formula
General
Surname Resveratrol
other names
  • trans -3,5,4'-trihydroxystilbene
  • 3,4 ', 5-stilbene triol
  • trans -resveratrol
  • ( E ) -5- ( p -hydroxystyryl) resorcinol
Molecular formula C 14 H 12 O 3
Brief description

white solid

External identifiers / databases
CAS number 501-36-0
EC number 610-504-8
ECHA InfoCard 100.121.386
PubChem 445154
ChemSpider 392875
DrugBank DB02709
Wikidata Q407329
properties
Molar mass 228.25 g · mol -1
Physical state

firmly

Melting point

254 ° C (decomposition)

safety instructions
GHS labeling of hazardous substances
05 - Corrosive 07 - Warning

danger

H and P phrases H: 302-315-317-318-335
P: 261-280-305 + 351 + 338
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Resveratrol is an organic compound with the empirical formula C 14 H 12 O 3 from the group of polyphenols . It is one of the phytoalexins with antioxidant properties.

History and naming

It was first described and named as resveratrol in Japan in 1939 by Michio Takaoka. He isolated the compound from the medicinal plant Veratrum grandiflorum . In 1963, resveratrol was isolated from the roots of Reynoutria japonica . The name resveratrol can be understood as a suitcase word which, due to the chemical relationship, is composed of the first syllable of the name of res orcinols , the generic name Veratrum and the systematic ending " -ol " for alcohols . In 1976, the successful detection of resveratrol in grapes .

Occurrence

Red grapes are particularly rich in resveratrol.

Both isomers of resveratrol exist in nature, the trans form being much more common and the cis form less common. In addition, there are also derived glucosides , which are also known as piceids .

3- β - D -glucopyranoside of resveratrol (piceid)

Resveratrol is found in a number of plants and plant foods, most notably in grapes , raspberries , mulberries , plums , peanuts, and Japanese knotweed . Resveratrol has been found in at least 72 species of plants. In red wine (especially in Pinot Noir and St. Laurent , regardless of the growing area) the concentration is high and higher than in white wine compared to other resveratrol sources. The concentration is between 0 and 14.3  mg / l trans -resveratrol. White wine and rosé contain lower concentrations of resveratrol, but proportionally more cis -resveratrol.

drink Resveratrol (mg / 100 ml)
Average Span
red wine 0.27 0 - 2.78
Rose wine 0.12 0.005-0.29
White wine 0.04 0.00-0.17
Sparkling wine 0.009 0.008 - 0.01
Grape juice (white) 0.00508 0.00 - 0.01

In its function as a phytoalexin, it protects plants from parasites and fungal infections in wet periods . It is mainly formed by the vines in the leaves and berry skins when attacked by downy mildew or botrytis . Stress, such as ultraviolet light, also leads to increased resveratrol formation.

properties

Resveratrol crystals under a polarizing microscope , with crossed polarizers.

Resveratrol is a white solid that is readily soluble in alcohol and oils and slightly soluble in water. Chemically, resveratrol is a stilbenoid , a derivative of stilbene . In plants it is produced under the catalytic action of the enzyme stilbene synthase .

Resveratrol comes as trans - and cis - isomer before. The trans form can be converted into the cis form under the action of UV radiation . trans -resveratrol is the more stable form of the two isomers.

Photoisomerization of resveratrol, the trans form on the left , the cis form on the right

Resveratrol survives the fermentation process and long storage times in the skin of grapes, such as in the marc .

biochemistry

Resveratrol has been identified as a pan-assay interference material that gives positive results in a wide variety of laboratory tests. Its ability to engage in multiple interactions can be due to direct effects on cell membranes. By 2015, many specific biological targets for resveratrol had been identified, including NQO2 (alone and in interaction with AKT1 ), GSTP1 , estrogen receptor beta, CBR1, and integrin αVβ . At the time, it was unclear whether one or all of these factors were responsible for the observed effects in cells and model organisms.

In vitro studies suggest that resveratrol activates sirtuin 1 , although this may be a directed effect from its immediate biological target (s). The signal transduction seems PGC-1α to run, which mitochondria are affected. An increase in the effect of MnSOD ( SOD2 ) and in GPER activity was observed in cells treated with resveratrol . In vitro, resveratrol was shown to be an agonist of peroxisome proliferator- activated receptor gamma ( PPARG ), a core receptor from pharmacological research for the possible treatment of type 2 diabetes. Resveratrol increases the concentrations of serum and bone alkaline phosphatase .

One way to administer resveratrol to humans is through direct absorption through saliva. However, the functionality of such an application method is unlikely due to the low water solubility of the molecule. The bioavailability of resveratrol is around 0.5% due to the extensive hepatic glucuronidation and sulfation . Resveratrol is largely metabolized in the body, with the liver and lungs being the primary sites of its metabolism.

effect

By 2019, decades of extensive research on resveratrol in numerous laboratory models of human diseases had shown no anti-disease effects in randomized clinical trials in humans. In-vitro studies have provided evidence of possible effectiveness against cancer cells . Other studies have shown positive effects of the substance in diseases such as arteriosclerosis , heart disease, Alzheimer's disease , arthritis and some autoimmune diseases .

longevity

To date, there is insufficient evidence that resveratrol has an effect on longevity in humans. A systematic review ( meta-analysis ) of existing resveratrol research in 2011 found that there was insufficient evidence of its effects on longevity or human disease, nor could there be any recommendations for intake in excess of what is commonly obtained from dietary sources, which was estimated to be less than 4 mg / day. Much of the studies with beneficial effects have been carried out on animals, with insufficient clinical research in humans. A meta-analysis was also carried out in 2012. Resveratrol is still being researched in animals and humans. Resveratrol, just like a low-calorie diet ( calorie restriction ), promotes the expression of sirtuin genes such as Sir2 . As a result, a life-prolonging effect was observed in some studies in various test animals. Several attempts to repeat these studies failed, but there was also a successful repeat. In an animal study, mice were given a particularly high-fat diet. The simultaneous administration of resveratrol significantly reduced the weight gain. With particularly high doses of resveratrol, a doubling of endurance performance was observed.

cancer

There is currently insufficient evidence that resveratrol has anti-cancer effects in humans. Even when high doses of resveratrol are used, the results of animal or human clinical studies on the effects of resveratrol on cancer are inconsistent. Resveratrol could help kill cancer cells by inhibiting a protein that is critical to cancer cell survival. This key protein, known as NF-κB (nuclear factor kappa B), is found in the nuclei of all cells. There it is responsible for activating genes that are responsible for cell survival. Resveratrol acts on NF-κB in such a way that it can no longer develop its survival-promoting effect. This in turn triggers apoptosis in the affected cancer cells . H. Self destruct one. Researchers hope that the use of NF-κB inhibitors such as resveratrol can significantly increase the effectiveness of established therapeutic approaches against cancer. However, the insolubility of resveratrol in water could still pose a problem: it may not be able to be absorbed by the body in sufficient quantities and so its effects against cancer and cardiovascular diseases may not develop sufficiently. The latest findings also show an effect of resveratrol on various cancer cells that is independent of NF-kB. In this way, it causes a reduction in the expression of the protein Bcl-2 , which protects the degenerated cells from cell death. At the same time, an increased expression of the proapoptotic protein Bax, which promotes cell death, was found.

When it comes to cancer, it must always be mentioned that most studies with resveratrol were done in vitro or in animal models. There is a lack of clinical trials and possible interactions with chemotherapy should always be considered and carefully considered. Two studies illustrate this aspect. In rats implanted with human cancer cells, resveratrol improved the effect of the chemotherapeutic agents cisplatin and doxorubicin and at the same time developed a cardioprotective effect, i.e. protected the heart cells from the toxicity of these active substances. If resveratrol was administered at the same time as the active ingredient paclitaxel (taxol) against cancer cells in vitro, it weakened the cancer-killing effect of paclitaxel. This is due to the fact that resveratrol inhibits the entry of cancer cells into the S phase of the cell cycle and the effect of paclitaxel unfolds precisely in this phase. Pretreatment of the cancer cells at an earlier point in time, i.e. prior to chemotherapy with paclitaxel, in turn led to a synergistic effect and caused increased cell death of the treated cancer cells.

Neurological Studies

Resveratrol is currently being investigated for its potential to limit sequelae after ischemia , such as stroke or acute brain trauma , and its possible effect on cognition . The activation of NF-κB also plays a role in the course of multiple sclerosis . NF-κB inhibitors could therefore also represent a therapeutic option here in the future. Resveratrol could have a neuroprotective effect in glaucoma . Increased intraocular pressure increases oxidative stress on the retina and trabecular meshwork. This leads to increased inflammation markers such as interleukin-1α, interleukin-6 , interleukin-8 and faster cell aging due to oxidative species such as lipofuscin in the cells of the trabecular meshwork and the optic nerve. Resveratrol reduces the expression of these substances and therefore has an antioxidant and antiapoptotic effect in the trabecular meshwork and in the neurons of the optic nerve.

Cardiovascular Studies

So far there is insufficient evidence of an effect of resveratrol in cardiovascular diseases. A 2015 meta-analysis found a decrease in systolic blood pressure of 11.9  mmHg with resveratrol doses of 150 mg / day. A 2018 meta-analysis, on the other hand, showed no effect on systolic or diastolic blood pressure ; a partial analysis showed a systolic pressure drop of 2 mmHg only due to resveratrol doses of 300 mg per day and only in diabetic people . A 2015 meta-analysis found no effect on systolic or diastolic blood pressure; an under-analysis found an 11.90 mmHg reduction in systolic blood pressure from resveratrol doses of 150 mg per day. In animal experiments, resveratrol was able to significantly reduce the aortic root diameter in mice with Marfan syndrome . Resveratrol has no effect on blood lipid levels .

diabetes

A 2015 review found little evidence of resveratrol's use to treat diabetes mellitus . A meta-analysis from 2015 found little evidence of an effect of resveratrol on diabetes biomarkers . There is insufficient evidence of an influence of resveratrol on metabolic syndrome .

skin

Despite extensive in vitro and animal research, there is no evidence that resveratrol, taken orally or topically , has any effect on human skin. Preliminary studies of resveratrol were conducted to investigate its potential as a therapy for melanoma .

Side effects

In a clinical study of Alzheimer's disease and resveratrol, the most common side effects were diarrhea , weight loss, and nausea . A study of blood pressure and resveratrol reported increased intestinal peristalsis and loose stools, and an itchy rash in one person.

trade

Resveratrol supplements can now be purchased over the counter in the USA as dietary supplements . Also in Germany are now resveratrol supplements, usually made of grape extract, produced and offered for sale. The pharmaceutical company GlaxoSmithKline bought the biotech company Sirtris, which specializes in the production of resveratrol and other active ingredients from the anti-aging sector, for US $ 720 million . But the hopes were not fulfilled, so that the group ended its commitment to resveratrol in 2011.

By introducing an additional stilbene synthase gene, Chinese scientists have developed a grape variety that has six times more resveratrol in red wine grapes than the original variety. The gene can also be introduced into other plants, which then produce resveratrol. This has been successfully carried out on an experimental basis with silver poplars ( Populus alba ).

literature

Web links

Commons : Resveratrol  - collection of pictures, videos and audio files

Individual evidence

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