Re: New grape seed extract

Does the grape seed extract contain significant amounts of
resversatrol?

I'm wondering if it would be beneficial or necessary to take both the
ActiVin product and a reversatrol product, the latter of which seems
to be derived from the grape skin.

Thanks


[EMAIL PROTECTED] (Thomas Carter) wrote in message news:<[EMAIL PROTECTED]>...
> Hi,
> 
>         IH636, commercially known as ActiVin is a grape seed extract.
> The first published paper on Pubmed was in '99. It is of course a
> proprietary herbal product and is now in a phase II cancer trial. It's
> been commercially available at a reasonable price for some time now
> and it's resume is impressive; organoprotective (1), hypolipodemic
> when given with chromium nicotinate, antiatherosclerotic, and
> cardioprotective (3) (4) (5), and lastly anticarcenogenic (6). The
> cholesterol study was in humans, and it shows comparative affects with
> some of the statins. In certain conditions it activates a powerful
> oncogene which gives some cause for concern (1b). Almost 20 million
> has been invested in studying this product but there is no published
> account of its efficazy compared to other grape seed extracts, which
> suggests there is no particular advantage to ActiVin.
>         This is a fine example of what can be accomplished in a short
> time by a determined, effort. We would all profit if the public sector
> could even on occasion perform half as well IMO.
> 
> (1) Res Commun Mol Pathol Pharmacol. 2000;107(1-2):105-28.  Related
> Articles, Links
> Unique organoprotective properties of a novel IH636 grape seed
> proanthocyanidin extract on cadmium chloride-induced nephrotoxicity,
> dimethylnitrosamine (DMN)-induced splenotoxicity and mocap-induced
> neurotoxicity in mice.
> Ray SD, Wong V, Rinkovsky A, Bagchi M, Raje RR, Bagchi D.
> Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long
> Island University, Brooklyn, NY 11201, USA. [EMAIL PROTECTED]
>                        Several observations, both in humans and
> laboratory animals, have suggested that proanthocyanidins exhibit a
> broad spectrum of pharmacological, therapeutic and chemoprotective
> properties. Specifically, some of our earlier studies have shown that
> IH636 grape seed proanthocyanidin extract (GSPE, commercially known as
> ActiVin) provides excellent concentration- and dose-dependent
> protection against toxicities induced by diverse agents, such as
> acetaminophen, hydrogen peroxide, 12-O-tetradecanoylphorbol-13-acetate
> (TPA), smokeless-tobacco extract, idarubicin and
> 4-hydroxyperoxycyclophosphamide in both in vitro and in vivo models.
> In some models, GSPE proved to be a better cytoprotectant than
> vitamins C, E and beta-carotene. The purpose of this investigation was
> three fold: (i) to indirectly assess the bioavailability of GSPE in
> multiple target organs, (ii) quantify GSPE's capacity to avert cadmium
> chloride (CdCl2)-induced nephrotoxicity, dimethylnitrosamine
> (DMN)-induced splenotoxicity and O-ethyl-S,S-dipropyl
> phosphorodithioate (MOCAP)-induced neurotoxicity, and lastly (iii) to
> evaluate possible mechanisms of protection in mice. In order to
> determine all these, three separate experiments were designed and each
> experiment consisted of four groups, such as vehicle control, GSPE
> alone, toxicant alone and GSPE + toxicant. GSPE was administered
> orally (100 mg/Kg) for 7-8 days prior to the toxicant exposure.
> Parameters of the analyses included evaluation of serum chemistry
> changes (ALT, BUN and CK), histopathology and integrity of genomic
> DNA, both quantitatively and qualitatively. Results indicate that GSPE
> preexposure prior to cadmium chloride and DMN provided near complete
> protection in terms of serum chemistry changes (ALT, BUN and CK) and
> inhibition of both forms of cell death. e.g., apoptosis and necrosis.
> DNA damage, a common denominator usually associated with both
> apoptosis and necrosis was significantly reduced by GSPE treatment.
> Histopathological examination of organs correlated strongly with the
> changes in serum chemistry and the DNA modification data.
> Surprisingly, MOCAP exposure showed symptoms of neurotoxicity coupled
> with serum chemistry changes in the absence of any significant genomic
> DNA damage or brain pathology. Although, GSPE appeared to partially
> protect the neural tissue, it powerfully antagonized MOCAP-induced
> mortality. Taken together, this study suggests that in vivo
> GSPE-preexposure may protect multiple target organs from a variety of
> toxic assaults induced by diverse chemical entities.PMID: 11334361
> 
> (1b) The most dramatic changes observed in this study were: (i)
> substantial increase in the expression of bcl-Xl in the liver by 7-day
> GSPE exposure alone; (ii) significant modification bcl-Xl expression
> by AAP alone; and (iii) dramatic inhibition of AAP-induced
> modification of bcl-Xl (phosphorylation?) expression by GSPE. In
> summary, these observations demonstrate that GSPE preexposure may
> significantly attenuate AAP-induced hepatic DNA damage, apoptotic and
> necrotic cell death of liver cells, and, most remarkably, antagonize
> the influence of AAP-induced changes in bcl-Xl expression in vivo.
> Copyright 1999 Academic Press. PMID: 10462439   (bcl-xl is an
> extremely potent oncogene, especially in conjunction with c-myc. They
> are both inhibited by curcummin.) PMID: 14559912 is one of many
> treating with the two.
>  
> (2)Toxicology. 2002 Oct 30;180(1):5-22.  
> Comment in: Toxicology. 2003 Apr 15;186(1-2):171-3; author reply
> 175-7.
> Cytotoxicity and oxidative mechanisms of different forms of chromium.
> Bagchi D, Stohs SJ, Downs BW, Bagchi M, Preuss HG.
> Department of Pharmacy Sciences, Creighton University School of
> Pharmacy and
> Health Professions, 2500 California Plaza, Omaha, NE 68178,
> [EMAIL PROTECTED]
>        Chromium exists mostly in two valence states in nature:
> hexavalent chromium
> [chromium(VI)] and trivalent chromium [chromium(III)]. Chromium(VI) is
> commonly
> used in industrial chrome plating, welding, painting, metal finishes,
> steel
> manufacturing, alloy, cast iron and wood treatment, and is a proven
> toxin,
> mutagen and carcinogen. The mechanistic cytotoxicity of chromium(VI)
> is not
> completely understood, however, a large number of studies demonstrated
> that
> chromium(VI) induces oxidative stress, DNA damage, apoptotic cell
> death and
> altered gene expression. Conversely, chromium(III) is essential for
> proper
> insulin function and is required for normal protein, fat and
> carbohydrate
> metabolism, and is acknowledged as a dietary supplement. In this
> paper,
> comparative concentration- and time-dependent effects of chromium(VI)
> and
> chromium(III) were demonstrated on increased production of reactive
> oxygen
> species (ROS) and lipid peroxidation, enhanced excretion of urinary
> lipid
> metabolites, DNA fragmentation and apoptotic cell death in both in
> vitro and in
> vivo models. Chromium(VI) demonstrated significantly higher toxicity
> as compared
> with chromium(III). To evaluate the role of p53 gene, the
> dose-dependent effects
> of chromium(VI) were assessed in female C57BL/6Ntac and p53-deficient
> C57BL/6TSG
> p53 mice on enhanced production of ROS, lipid peroxidation and DNA
> fragmentation
> in hepatic and brain tissues. Chromium(VI) induced more pronounced
> oxidative
> damage in multiple target organs in p53 deficient mice. Comparative
> studies of
> chromium(III) picolinate and niacin-bound chromium(III), two popular
> dietary
> supplements, reveal that chromium(III) picolinate produces
> significantly more
> oxidative stress and DNA damage. Studies have implicated the toxicity
> of
> chromium picolinate in renal impairment, skin blisters and pustules,
> anemia,
> hemolysis, tissue edema, liver dysfunction; neuronal cell injury,
> impaired
> cognitive, perceptual and motor activity; enhanced production of
> hydroxyl
> radicals, chromosomal aberration, depletion of antioxidant enzymes,
> and DNA
> damage. Recently, chromium picolinate has been shown to be mutagenic
> and
> picolinic acid moiety appears to be responsible as studies show that
> picolinic
> acid alone is clastogenic. Niacin-bound chromium(III) has been
> demonstrated to
> be more bioavailable and efficacious and no toxicity has been
> reported. In
> summary, these studies demonstrate that a cascade of cellular events
> including
> oxidative stress, genomic DNA damage and modulation of apoptotic
> regulatory gene
> p53 are involved in chromium(VI)-induced toxicity and carcinogenesis.
> The safety
> of chromium(III) is largely dependent on the ligand, and adequate
> clinical
> studies are warranted to demonstrate the safety and efficacy of
> chromium(III)
> for human consumption. PMID: 12324196???????????..
> Med. 2000;31(5-6):227-46. 
> (3) Effects of niacin-bound chromium and grape seed proanthocyanidin
> extract on the
> lipid profile of hypercholesterolemic subjects: a pilot study.Preuss
> HG, Wallerstedt D, Talpur N, Tutuncuoglu SO, Echard B, Myers A, Bui M,
> Bagchi D.
> Department of Physiology, Georgetown University Medical Center,
> Washington, DC
> 20007, USA.
>     Hypercholesterolemia, a significant cardiovascular risk factor, is
> prevalent in
> the American population. Many drugs lower circulating cholesterol
> levels, but
> they are not infrequently associated with severe side effects.
> Accordingly,
> natural means to lower cholesterol levels safely would be welcomed. We
> examined
> 40 hypercholesterolemic subjects (total cholesterol 210-300 mg/dL) in
> a
> randomized, double-blind, placebo-controlled study. The four groups of
> ten
> subjects received either placebo bid, chromium polynicotinate (Cr) 200
> microg
> bid, grape seed extract (GSE) 100 mg bid, or a combination of Cr and
> GSE at the
> same dosage bid. Over two months, the average percent change +/- SEM
> in the
> total cholesterol from baseline among groups was: placebo -3.5% +/- 4,
> GSE -2.5%
> +/- 2, Cr -10% +/- 5, and combination -16.5% +/- 3. The decrease in
> the last
> group was significantly different from placebo (p < 0.01). The major
> decrease in
> cholesterol concentration was in the LDL levels: placebo -3.0% +/- 4,
> GSE -1.0%
> +/- 2.0, Cr -14% +/- 4.0, and the combination -20% +/- 6.0. Again, the
> combination of Cr and GSE significantly decreased LDL when compared to
> placebo
> (p<0.01). HDL levels essentially did not change among the groups.
> Also, there
> was no significant difference in the triglyceride concentrations among
> the
> groups; and no statistically significant differences were seen in the
> levels of
> autoantibodies to oxidized LDL (Ox-LDL). However, the trend was for
> the two
> groups receiving GSE to have greater decreases in the latter
> parameter, i.e.,
> -30.7% and -44.0% in the GSE and combined groups in contrast to -17.3%
> and
> -10.4% in the placebo and chromium groups. We determined the number of
> subjects
> in each group who decreased autoantibodies to oxidized LDL greater
> than 50% over
> eight weeks and found these ratios among groups: placebo = 2/9, Cr =
> 1/10, GSE =
> 6/10, and combined = 3/8. Thus, 50% of subjects (9/18) receiving GSE
> had a
> greater than 50% decrease in autoantibodies compared to 16% (3/19) in
> the two
> groups not receiving GSE. No significant changes occurred in the
> levels of
> circulating homocysteine and blood pressure among the four groups. We
> conclude
> that a combination of Cr and GSE can decrease total cholesterol and
> LDL levels
> significantly. Furthermore, there was a trend to decrease the
> circulating
> autoantibodies to oxidized LDL in the two groups receiving GSE. PMID:
> 11508317
> 
> (4) Mol Cell Biochem. 2002 Nov;240(1-2):99-103.
> Beneficial effects of a novel IH636 grape seed proanthocyanidin
> extract and a
> niacin-bound chromium in a hamster atherosclerosis model.
> Vinson JA, Mandarano MA, Shuta DL, Bagchi M, Bagchi D.
> Department of Chemistry, University of Scranton, Scranton, PA
> 18510-4626, USA.
> [EMAIL PROTECTED]
>     Atherosclerosis is a disease of the arteries in which fatty
> plaques develop on
> the inner arterial wall, which eventually obstructs blood flow.
> Identified risk
> factors for atherosclerosis include genetics, diet, lifestyle,
> smoking,
> circulating lipid and cholesterol levels, and molecular and
> circulating signals
> of chronic vascular inflammation. The link between flavonoids and
> atherosclerosis is based partly on the evidence that some flavonoids
> possess
> antioxidant properties and have been shown to be potent inhibitors of
> LDL
> oxidation in vitro. Hypercholesterolemia, a significant cardiovascular
> risk
> factor is prevalent in the American population. Grape seed
> proanthocyanidin
> extracts are known to exhibit a broad spectrum of chemopreventive and
> cardioprotective properties against oxidative stress. A recent study
> has shown
> that a combination of IH636 grape seed proanthocyanidin extract (GSPE)
> and a
> niacin-bound chromium (NBC) can decrease total cholesterol, LDL and
> oxidized LDL
> levels in hypercholesterolemic human subjects. In this study, we
> assessed the
> efficacy of GSPE supplementation in hamsters, singly and in
> combination with
> NBC, since these animals have a similar lipid profile to
> hypercholesterolemic
> humans when fed a hypercholesterolemic diet of 0.2% cholesterol and
> 10% coconut
> oil (HCD). After 10 weeks of feeding HCD, these animals developed foam
> cells,
> which is a biomarker of early stages of atherosclerosis.
> Atherosclerosis (% of
> aorta covered with foam cells) was reduced by approximately 50% and
> 63%
> following supplementation of these animals with 50 mg/kg and 100 mg/kg
> of GSPE,
> respectively, in conjunction with a HCD, while approximately 32%
> reduction was
> observed following supplementation of GSPE plus NBC. A range of 7-9
> animals was
> used in each study group. GSPE alone and in combination with NBC
> exerted a
> pronounced effect on the cholesterol, and triglyceride levels, as well
> as
> oxidative lipid damage as demonstrated by the formation of
> thiobarbituric acid
> reactive substances (TBARS). This data demonstrates that GSPE and NBC
> may
> provide significant health benefits by dramatically ameliorating the
> incidence
> of atherosclerosis as demonstrated by reducing the formation of foam
> cells.
> PMID: 12487376
> (5) Mutat Res. 2003 Feb-Mar;523-524:87-97.  Related Articles, Links   
> Molecular mechanisms of cardioprotection by a novel grape seed
> proanthocyanidin extract.
> Bagchi D, Sen CK, Ray SD, Das DK, Bagchi M, Preuss HG, Vinson JA.
> Department of Pharmacy Sciences, Medical Center, School of Pharmacy
> and Creighton University Health Professions, 2500 California Plaza,
> Omaha, NE 68178, USA. [EMAIL PROTECTED]
>         Free radicals and oxidative stress play a crucial role in the
> pathophysiology of a broad spectrum of cardiovascular diseases
> including congestive heart failure, valvular heart disease,
> cardiomyopathy, hypertrophy, atherosclerosis and ischemic heart
> disease. We have demonstrated that IH636 grape seed proanthocyanidin
> extract (GSPE) provides superior antioxidant efficacy as compared to
> Vitamins C, E and beta-carotene. A series of studies were conducted
> using GSPE to demonstrate its cardioprotective ability in animals and
> humans. GSPE supplementation improved cardiac functional assessment
> including post-ischemic left ventricular function, reduced myocardial
> infarct size, reduced ventricular fibrillation (VF) and tachycardia,
> decreased the amount of reactive oxygen species (ROS) as detected by
> ESR spectroscopy and reduced malondialdehyde (MDA) formation in the
> heart perfusate. Cardiomyocyte apoptosis detected by terminal
> deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL)
> staining. In concert, the proapoptotic signals mediated by JNK-l and
> c-fos proteins were also reduced suggesting that the novel
> cardioprotective properties of GSPE may be at least partially
> attributed to its ability to block anti-death signaling mediated
> through the proapoptotic transcription factors and genes such as JNK-1
> and c-JUN. In a separate study, GSPE pretreatment significantly
> inhibited doxorubicin-induced cardiotoxicity as demonstrated by
> reduced serum creatine kinase (CK) activity, DNA damage and
> histopathological changes in the cardiac tissue of mice.
> Concentration-dependent efficacy of GSPE was also assessed in a
> hamster atherosclerosis model. Approximately 49 and 63% reduction in
> foam cells, a biomarker of early stage atherosclerosis, were observed
> following supplementation of 50 and 100 mg GSPE/kg body weight,
> respectively. A human clinical trial was conducted on
> hypercholesterolemic subjects. GSPE supplementation significantly
> reduced oxidized LDL, a biomarker of cardiovascular diseases. Finally,
> a cDNA microarray study demonstrated significant inhibition of
> inducible endothelial CD36 expression, a novel cardioregulatory gene,
> by GSPE. These results demonstrate that GSPE may serve as a potential
> therapeutic tool in promoting cardiovascular health via a number of
> novel mechanisms. Copyright 2003 Elsevier Science B.V.PMID: 12628506
> 
> (6)  Mol Cell Biochem. 1999 Jun;196(1-2):99-108.  Related Articles,
> Links
> The cytotoxic effects of a novel IH636 grape seed proanthocyanidin
> extract on cultured human cancer cells.
> Ye X, Krohn RL, Liu W, Joshi SS, Kuszynski CA, McGinn TR, Bagchi M,
> Preuss HG, Stohs SJ, Bagchi D.
> Creighton University School of Pharmacy and Allied Health Professions,
> Omaha, NE 68178, USA.
>          Grape seed proanthocyanidins are natural antioxidants which
> possess a broad spectrum of chemoprotective properties against free
> radicals and oxidative stress. In this study, we have assessed the
> cytotoxicity of a novel IH636 grape seed proanthocyanidin extract
> (GSPE) against MCF-7 human breast cancer cells, A-427 human lung
> cancer cells, CRL-1739 human gastric adenocarcinoma cells and K562
> chronic myelogenous leukemic cells at 25 and 50 mg/lit concentrations
> for 0-72 h using cytomorphology and MTT cytotoxicity assay. In
> addition, we compared the effects on normal human gastric mucosal
> cells and normal J774A.1 murine macrophage cells with the effects on
> the cancer cell lines. Concentration- and time-dependent cytotoxic
> effects of GSPE were observed on the MCF-7 breast cancer, A-427 lung
> cancer and gastric adenocarcinoma cells. Following incubation of the
> MCF-7 cells with 25 mg/lit of the GSPE approximately 6.5, 30 and 43%
> inhibitions in cell growth were observed at 24, 48 and 72 h of
> incubation, respectively, while incubation of the MCF-7 cells with 50
> mg/lit of the GSPE resulted in 11, 35 and 47% inhibition in cell
> growth at these same points, respectively. Similar results were
> observed in the A-427 and gastric adenocarcinoma cells. GSPE exhibited
> no cytotoxicity toward the neoplastic K562 myelogenous leukemic cells.
> However, GSPE enhanced the growth and viability of the normal human
> gastric mucosal cells and J774A.1 murine macrophage cells. These data
> demonstrate that GSPE exhibited cytotoxicity towards some cancer
> cells, while enhancing the growth and viability of the normal cells
> which were examined.PMID: 10448908
> It's nontoxic  PMID: 11758648
> 
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