Resveratrol Study Thread

[DAdams91982]

As my first step in as a rep, I would like to highlight some of the studies surrounding Resveratol. So you can see why IBE took the reighs, and developed a bioavailable Reservatrol Product.

First lets hit on Antioxidant activity.

Resveratrol effectively scavenges free radicals and other oxidants and inhibits low density lipoprotein oxidation.

Efficiency and mechanism of the antioxidant action of trans-resveratrol and its analogues in the radical liposome oxidation.

Stojanović S, Sprinz H, Brede O.

Research Unit Time-Resolved Spectroscopy, University of Leipzig, Permoserstrasse 15, D-04318 Leipzig, Germany.

trans-Resveratrol (trans-3,5,4'-trihydroxystilbene) is a nonflavonoid polyphenol reported to exert different biological activities, among them inhibition of the lipid peroxidation, scavenging of the free radicals, inhibition of the platelet aggregation, and anticancer activity as the most important. In order to enlighten the radical-scavenging mechanism of trans-resveratrol, stationary gamma-radiolytic experiments in liposomes and pulse radiolytic experiments in aqueous solutions were performed. Applying the stationary gamma-radiolysis together with the subsequent product analysis, reactions of lipid peroxyl radicals, LOO*, with trans-resveratrol and other natural antioxidants were investigated. It was found that trans-resveratrol was a better radical scavenger than vitamins E and C but similar to the flavonoids epicatechin and quercetin. The comparison of the radical-scavenging effects of trans-resveratrol and its analogues trans-4-hydroxystilbene and trans-3,5-dihydroxystilbene revealed that trans-resveratrol and trans-4-hydroxystilbene showed almost the same effect and were more efficient than trans-3,5-dihydroxystilbene. These findings indicate greater radical-scavenging activity of trans-resveratrols para-hydroxyl group than its meta-hydroxyl groups. Using the pulse radiolysis, reactions of trans-resveratrol and its analogues with trichloromethylperoxyl radicals, CCl(3)OO*, were studied. Spectral and kinetic properties of the observed transients showed great similarity between trans-resveratrol and trans-4-hydroxystilbene which seems to confirm that para-hydroxyl group of trans-resveratrol scavenges free radicals more effectively than its meta-hydroxyl groups. Copyright 2001 Academic Press.

The interaction of resveratrol with ferrylmyoglobin and peroxynitrite; protection against LDL oxidation.

Brito P, Almeida LM, Dinis TC.

Laboratório de Bioquímica, Faculdade de Farmácia, Universidade de Coimbra and Centro de Neurociências, Couraça dos Apóstolos, 51, r/c, 3000-295 Coimbra, Portugal.

Resveratrol (3,4',5-trihydroxystilbene) is a natural phytoalexin synthesized in response to injury or fungal attack, found in the grape skin and wine, specially red wine. A large number of studies have demonstrated that resveratrol regulates many biological activities, namely protection against atherosclerosis by a set of pharmacological properties, including the antioxidant activity. In this study, we explored the capacity of resveratrol in protecting low density lipoproteins (LDL) against either ferrylmyoglobin- or peroxynitrite-mediated oxidation and the underlying mechanisms of its antioxidant potential. Resveratrol efficiently decreases the accumulation of hydroperoxides in LDL promoted by ferrylmyoglobin, a potent oxidant formed by the reaction of metmyoglobin with hydrogen peroxide, in a concentration-dependent manner, promptly reducing the oxoferryl complex to metmyoglobin. Simultaneously, resveratrol is consumed as detected by the rapid decrease in the characteristic peak at 310 nm, in a similar way to that observed upon its reaction with peroxidase/H2O2, pointing to a mechanism of one-electron oxidation and subsequent resveratrol dimer formation. On the other hand, resveratrol inhibits LDL apoprotein modifications induced by peroxynitrite, another potent oxidant formed by the reaction between superoxide and nitric oxide, as assessed by the decrease in apo-B net charge alterations and in carbonyl groups formation mediated by that oxidant. Resveratrol also interacts with peroxynitrite in a similar way to that observed with laccases, suggesting a mechanism of resveratrol oxidation rather than a nitration one. These mechanisms are discussed. Considering that either ferrylmyoglobin or peroxynitrite are physiologically relevant oxidants implicated in several pathologies, including atherosclerosis, our results certainly contribute to the understanding of the antioxidant action of resveratrol and consequently provide a new approach for the cardiovascular benefits associated with moderate consumption of red wine.

Couldn't find the abstract for this one, so if any can pull this it would be appreciated

Inhibition of human LDL oxidation by resveratrol

E. N. Frankel, A. L. Waterhouse and J. E. Kinsella

Departments of Food Science and Technology, and Viticulture and Enology, University of California, Davis, California 95616, U.S.A

SIR,--Oxidation of low density lipoproteins (LDL) is a crucial step in the pathogenesis of atherosclerosis.l Dietary antioxidants
that can inhibit the oxidation of LDL are receiving considerable attention for their role in the prevention of coronary heart disease.2
Because phenolic substances in red wine inhibit the coppercatalysed oxidation of human LDL in vitro,3 we proposed (Feb 20, p 454) that the antioxidant activity of these compounds may explain the "French paradox". Resveratrol (3, 4’, 5-trihydroxystilbene) has attracted interest4 because it is present in wine and its glucoside is
reported to be the active ingredient of the oriental folk medicine kojo-kon which is used for a multitude of therapeutic purposes.5

Resveratrol has been suggested as the active ingredient of wine that may explain the French paradox,4 yet no direct evidence has linked it to any beneficial effect in man. We studied the antioxidant potency of synthetic transresveratrol, and found that it protects human LDL against copper-catalysed oxidation. Peroxidation, measured by hexanal formation, was inhibited by 81% and 70% in LDL from two healthy adult volunteers by the addition of 10 µmol/L of resveratrol. By comparison, the addition of extracts of a red wine (California Petit Syrah), diluted 1000-fold with water, and containing 10 µmol/L of total phenols, inhibited LDL oxidation by 61 % and 48%. The two pentahydroxy flavonoid compounds, epicatechin and quercetin, also found in wine, had about twice the inhibiting potency of resveratrol. In contrast, 10 JlffioljL of a-tocopherol, which has been associated with a reduced risk of cardiac disease, had a much lower antioxidant potency than resveratrol, inhibiting LDL oxidation by only 40% and 19% (figure).

These studies support previous work,3 and suggest that the combination of phenolic compounds in wine may protect against atherogenesis by their antioxidant effects over a prolonged period of consumption. It is noteworthy that the concentration of epicatechin and its isomers typically exceeds 15 mg/L in white and 150 mg/L in red wine, and quercetin averages 25 mg/L in red wine, whereas resveratrol concentrations are typically below 1 mg/L .4 Thus, resveratrol may not be the most important component in wine in reducing heart disease. Other common phenolics, epicatechin and quercetin, are more potent inhibitors of LDL oxidation, and may have a greater impact on health. Our data provide a plausible explanation for the assumed health benefits of wine consumption, but more information is needed on the absorption of resveratrol and other wine phenolics to assess their role in reducing coronary heart
disease.

 

[DAdams91982]

Inhibition of Proliferation and Induction of Apoptosis

Cancer cells proliferate rapidly and are unable to respond to cell death signals that inititate apoptosis. Resveratrol has been found to inhibit proliferation and induce apoptosis in a number of cancer cell lines

Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies.

Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y.

Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Box 143, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. [email protected]

Resveratrol, trans-3,5,4'-trihydroxystilbene, was first isolated in 1940 as a constituent of the roots of white hellebore (Veratrum grandiflorum O. Loes), but has since been found in various plants, including grapes, berries and peanuts. Besides cardioprotective effects, resveratrol exhibits anticancer properties, as suggested by its ability to suppress proliferation of a wide variety of tumor cells, including lymphoid and myeloid cancers; multiple myeloma; cancers of the breast, prostate, stomach, colon, pancreas, and thyroid; melanoma; head and neck squamous cell carcinoma; ovarian carcinoma; and cervical carcinoma. The growth-inhibitory effects of resveratrol are mediated through cell-cycle arrest; upregulation of p21Cip1/WAF1, p53 and Bax; down-regulation of survivin, cyclin D1, cyclin E, Bcl-2, Bcl-xL and clAPs; and activation of caspases. Resveratrol has been shown to suppress the activation of several transcription factors, including NF-kappaB, AP-1 and Egr-1; to inhibit protein kinases including IkappaBalpha kinase, JNK, MAPK, Akt, PKC, PKD and casein kinase II; and to down-regulate products of genes such as COX-2, 5-LOX, VEGF, IL-1, IL-6, IL-8, AR and PSA. These activities account for the suppression of angiogenesis by this stilbene. Resveratrol also has been shown to potentiate the apoptotic effects of cytokines (e.g., TRAIL), chemotherapeutic agents and gamma-radiation. Phamacokinetic studies revealed that the target organs of resveratrol are liver and kidney, where it is concentrated after absorption and is mainly converted to a sulfated form and a glucuronide conjugate. In vivo, resveratrol blocks the multistep process of carcinogenesis at various stages: it blocks carcinogen activation by inhibiting aryl hydrocarbon-induced CYP1A1 expression and activity, and suppresses tumor initiation, promotion and progression. Besides chemopreventive effects, resveratrol appears to exhibit therapeutic effects against cancer. Limited data in humans have revealed that resveratrol is pharmacologically quite safe. Currently, structural analogues of resveratrol with improved bioavailability are being pursued as potential therapeutic agents for cancer

Resveratrol modulation of signal transduction in apoptosis and cell survival: a mini-review.

Fulda S, Debatin KM.

University Children's Hospital, Eythstr. 24, 89075 Ulm, Germany. [email protected]

BACKGROUND: There is mounting evidence in the literature that resveratrol is a promising natural compound for prevention and treatment of a variety of human cancers. This overview summarizes recent studies of the major apoptosis and survival pathways regulated by resveratrol. BIOLOGICAL MECHANISMS: Apoptosis or programmed cell death is a key regulator of tissue homeostasis during normal development and also in adult organism under various conditions including adaptive responses to cellular stress. For example, tissue homeostasis is maintained by tight control of signaling events regulating cell death and survival. Thus, uncontrolled proliferation or failure to undergo cell death is involved in pathogenesis and progression of many human diseases, for example in tumorigenesis or in cardiovascular disorders. Moreover, current cancer therapies primarily act by triggering apoptosis programs in cancer cells. THERAPEUTIC APPLICATIONS: Natural products such as resveratrol have gained considerable attention as cancer chemopreventive or cardioprotective agents and also because of their antitumor properties. Among its wide range of biological activities, resveratrol has been reported to interfere with many intracellular signaling pathways, which regulate cell survival or apoptosis. DISCUSSION: Further insights into the signaling network and interaction points modulated by resveratrol may provide the basis for novel drug discovery programs to exploit resveratrol for the prevention and treatment of human diseases.

 

[RenegadeRows]

Good info!!!!!

 

[Steveoph]

DA there IS no abstract for that article you mentioned. Here is however the text

SIR,--Oxidation of low density lipoproteins (LDL) is a crucial step in the pathogenesis of atherosclerosis.l Dietary antioxidants
that can inhibit the oxidation of LDL are receiving considerable attention for their role in the prevention of coronary heart disease.2
Because phenolic substances in red wine inhibit the coppercatalysed oxidation of human LDL in vitro,3 we proposed (Feb 20, p 454) that the antioxidant activity of these compounds may explain the "French paradox". Resveratrol (3, 4’, 5-trihydroxystilbene) has attracted interest4 because it is present in wine and its glucoside is
reported to be the active ingredient of the oriental folk medicine kojo-kon which is used for a multitude of therapeutic purposes.5

Resveratrol has been suggested as the active ingredient of wine that may explain the French paradox,4 yet no direct evidence has linked it to any beneficial effect in man. We studied the antioxidant potency of synthetic transresveratrol, and found that it protects human LDL against copper-catalysed oxidation. Peroxidation, measured by hexanal formation, was inhibited by 81% and 70% in LDL from two healthy adult volunteers by the addition of 10 µmol/L of resveratrol. By comparison, the addition of extracts of a red wine (California Petit Syrah), diluted 1000-fold with water, and containing 10 µmol/L of total phenols, inhibited LDL oxidation by 61 % and 48%. The two pentahydroxy flavonoid compounds, epicatechin and quercetin, also found in wine, had about twice the inhibiting potency of resveratrol. In contrast, 10 JlffioljL of a-tocopherol, which has been associated with a reduced risk of cardiac disease, had a much lower antioxidant potency than resveratrol, inhibiting LDL oxidation by only 40% and 19% (figure).

These studies support previous work,3 and suggest that the combination of phenolic compounds in wine may protect against atherogenesis by their antioxidant effects over a prolonged period of consumption. It is noteworthy that the concentration of epicatechin and its isomers typically exceeds 15 mg/L in white and 150 mg/L in red wine, and quercetin averages 25 mg/L in red wine, whereas resveratrol concentrations are typically below 1 mg/L .4 Thus, resveratrol may not be the most important component in wine in reducing heart disease. Other common phenolics, epicatechin and quercetin, are more potent inhibitors of LDL oxidation, and may have a greater impact on health. Our data provide a plausible explanation for the assumed health benefits of wine consumption, but more information is needed on the absorption of resveratrol and other wine phenolics to assess their role in reducing coronary heart
disease.

 

[LakeMountD]

Steveo, quercetin may help more with preventing ldl oxidation but quercetin effects SIRT1 in a negative way, therefore negating the possible life extending benefits of resveratrol.

 

[Mass_69]

That's funny because Ergopharm added quercetin to 6-OXO Extreme to enhance the resveratrol bioavailability. :lol:

 

[LakeMountD]

That's funny because Ergopharm added quercetin to 6-OXO Extreme to enhance the resveratrol bioavailability. :lol:

Yeah, I mean it does do that. You can use a few other things as well, but they are marketing it as a SERM so they could care less about SIRT1 effects. Trying to use Res as a SERM is like trying to eat cereal with a fork. It may work, but there are better options for eating cereal and better options for using the fork. (I think this might go in someone's sig lol) :afro:

 

[Steveoph]

Yeah, I mean it does do that. You can use a few other things as well, but they are marketing it as a SERM so they could care less about SIRT1 effects. Trying to use Res as a SERM is like trying to eat cereal with a fork. It may work, but there are better options for eating cereal and better options for using the fork. (I think this might go in someone's sig lol) :afro:

Yea there's many compounds out there that have a week AI effect, but their main function isn't that. It could be beneficial on the side, but it shouldn't be marketed for that function. It's like Grape Seed Extract which has AI properties, but I take it more for the overall health/antioxidant benefits and give a nod to the AI ability.

 

[DAdams91982]

Well I am gone for a few days an this.

Steveo, as LMD said so eliquontly with 1/3 the tact of myself, the pubs were intended to highlight the benefits of Res, not to compare it to others. Whereas one product may out do a fascete (sp?) of Res, it could never touch the abundance of benefits Res holds.

Man that was hard to type... d@mn ambien kickin me in the frontal lobe.

Adams

 

[DAdams91982]

Effects on Biotransformation Enzymes

Some compounds only become carcinogenic when they have been metabolized in the body by cytochrome P450 enzymes.

Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies.

Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y.

Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Box 143, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. [email protected]

Resveratrol, trans-3,5,4'-trihydroxystilbene, was first isolated in 1940 as a constituent of the roots of white hellebore (Veratrum grandiflorum O. Loes), but has since been found in various plants, including grapes, berries and peanuts. Besides cardioprotective effects, resveratrol exhibits anticancer properties, as suggested by its ability to suppress proliferation of a wide variety of tumor cells, including lymphoid and myeloid cancers; multiple myeloma; cancers of the breast, prostate, stomach, colon, pancreas, and thyroid; melanoma; head and neck squamous cell carcinoma; ovarian carcinoma; and cervical carcinoma. The growth-inhibitory effects of resveratrol are mediated through cell-cycle arrest; upregulation of p21Cip1/WAF1, p53 and Bax; down-regulation of survivin, cyclin D1, cyclin E, Bcl-2, Bcl-xL and clAPs; and activation of caspases. Resveratrol has been shown to suppress the activation of several transcription factors, including NF-kappaB, AP-1 and Egr-1; to inhibit protein kinases including IkappaBalpha kinase, JNK, MAPK, Akt, PKC, PKD and casein kinase II; and to down-regulate products of genes such as COX-2, 5-LOX, VEGF, IL-1, IL-6, IL-8, AR and PSA. These activities account for the suppression of angiogenesis by this stilbene. Resveratrol also has been shown to potentiate the apoptotic effects of cytokines (e.g., TRAIL), chemotherapeutic agents and gamma-radiation. Phamacokinetic studies revealed that the target organs of resveratrol are liver and kidney, where it is concentrated after absorption and is mainly converted to a sulfated form and a glucuronide conjugate. In vivo, resveratrol blocks the multistep process of carcinogenesis at various stages: it blocks carcinogen activation by inhibiting aryl hydrocarbon-induced CYP1A1 expression and activity, and suppresses tumor initiation, promotion and progression. Besides chemopreventive effects, resveratrol appears to exhibit therapeutic effects against cancer. Limited data in humans have revealed that resveratrol is pharmacologically quite safe. Currently, structural analogues of resveratrol with improved bioavailability are being pursued as potential therapeutic agents for cancer

Inhibiting the expression and activity of certain P450 enzymes, resveratrol could help prevent cancer by reducing exposure to activated carcinogens.

Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells.

Chen ZH, Hurh YJ, Na HK, Kim JH, Chun YJ, Kim DH, Kang KS, Cho MH, Surh YJ.

College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.

Resveratrol (3,5,4'-trihydroxystilbene), a naturally occurring phytoalexin present in grapes and other foods, has been reported to possess chemopreventive effects as revealed by its striking inhibition of diverse cellular events associated with tumor initiation, promotion and progression. In our present study, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), when treated with the cultured human mammary epithelial (MCF-10A) cells, induced the expression of cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1) that are responsible for the oxidation of 17beta-estradiol to produce catechol estrogens. Resveratrol strongly inhibited the TCDD-induced aryl hydrocarbon receptor (AhR) DNA binding activity, the expression of CYP1A1 and CYP1B1 and their catalytic activities in MCF-10A cells. It also reduced the formation of 2-hydroxyestradiol and 4-hydroxyestradiol from 17beta-estradiol by recombinant human CYP1A1 and CYP1B1, respectively. Furthermore, resveratrol significantly attenuated the intracellular reactive oxygen species (ROS) formation and oxidative DNA damage as well as the cytotoxicity induced by the catechol estrogens. Our data suggest that CYP1A1- and CYP1B1-catalyzed catechol estrogen formation might play a key role in TCDD-induced oxidative damage, and resveratrol can act as a potential chemopreventive against dioxin-induced human mammary carcinogenesis by blocking the metabolic formation of the catechol estrogens and scavenging the ROS generated during their redox cycling.

Inhibition of aryl hydrocarbon-induced cytochrome P-450 1A1 enzyme activity and CYP1A1 expression by resveratrol.

Ciolino HP, Yeh GC.

Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute, Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, Maryland 21702-1201, USA. [email protected]

We investigated the effect of resveratrol, a constituent of the human diet that has been shown to inhibit aryl hydrocarbon-induced carcinogenesis in animals, on the carcinogen activation pathway regulated by the aryl hydrocarbon receptor. Resveratrol inhibited the metabolism of the environmental aryl hydrocarbon benzo[a]pyrene (B[a]P) catalyzed by microsomes isolated from B[a]P-treated human hepatoma HepG2 cells. Resveratrol competitively inhibited, in a concentration-dependent manner, the activity of the carcinogen activating enzymes cytochrome P-450 (CYP)1A1/CYP1A2 in microsomes and intact HepG2 cells. Resveratrol inhibited the B[a]P-induced expression of the CYP1A1 gene, as measured at the mRNA and transcriptional levels. Resveratrol abolished the binding of B[a]P-activated nuclear aryl hydrocarbon receptor to the xenobiotic-responsive element of the CYP1A1 promoter but did not itself bind to the receptor. Resveratrol was also effective in inhibiting CYP1A1 transcription induced by the aryl hydrocarbon dimethylbenz[a]anthracene in human mammary carcinoma MCF-7 cells. These data demonstrate that resveratrol inhibits aryl hydrocarbon-induced CYP1A activity in vitro by directly inhibiting CYP1A1/1A2 enzyme activity and by inhibiting the signal transduction pathway that up-regulates the expression of carcinogen activating enzymes. These activities may be an important part of the chemopreventive activity of resveratrol in vivo.

Some more info to bake ya'lls noodles.

Be ready.

 

[Steveoph]

Well I am gone for a few days an this.

Steveo, as LMD said so eliquontly with 1/3 the tact of myself, the pubs were intended to highlight the benefits of Res, not to compare it to others. Whereas one product may out do a fascete (sp?) of Res, it could never touch the abundance of benefits Res holds.

Man that was hard to type... d@mn ambien kickin me in the frontal lobe.

Adams

Got your drift I just typically highlight the conclusions of articles that I post. I'm definitely intrigued by the benefits on resveratrol.

 

[LakeMountD]

Well I am gone for a few days an this.

Steveo, as LMD said so eliquontly with 1/3 the tact of myself, the pubs were intended to highlight the benefits of Res, not to compare it to others. Whereas one product may out do a fascete (sp?) of Res, it could never touch the abundance of benefits Res holds.

Man that was hard to type... d@mn ambien kickin me in the frontal lobe.

Adams

Man when I get on Ambien I do A LOT of things I don't remember. :fool2:

 

[Thanos]

Man when I get on Ambien I do A LOT of things I don't remember. :fool2:

LOL! Join the crowd

 

[poopypants]

bump on this thread!


I though I heard something bout old peoples diseases being prevented via resveritrol due to its anti Ox properties ut now cant find it....

Any definitive studies linking oxidative stress to such things as parkinson's and alzhiemer's?

This would go hand in hand that such a potent anti OX would in turn help to prevent either of these nervous disorders found mostly in older folks.....

 

[LMR]

How is REVERSE in comparison to Alpha Lipoic Acid as a super anti-oxidant?

 

[tuberman]

I've been going to the library and Borders to check out some of the book info on SIRT1 enzyme expression and its effects on mitochondria replication and protection. They covered both the use of resveratrol and calorie deprivation (CD). The animals on the CD diet were low on energy for a couple of weeks or a little more, and then their energy quickly picked up despite the low calorie diet. The resveratrol studies showed fat little animals as animated and athletically active as slender ones within a few weeks. The high-calorie diet mice on resveratrol lived about 30% longer than they typically would have.

The studies in those books were focused on the SIRT 1 and it's effects on genes that lengthen life through the creation of extra energy potential though the greater amount of mitochondria (and therefore, ATP) in cells, and the improved health of those mitochondria.

 

[tuberman]

I'm going to let you people get on with your scientific abstractions.

I got carried away with my enthusiasm for your new product, and wanted to connect a few dots for why BB and weight trainers should care. I won't let such naive enthusiasm for IBE happen again.