Grape Seed Extract-100
- For Dogs and Cats
A nutritional supplement for the immune system, circulatory
functions, and skin health. Grape seed extract supplement that is
standardized to yield 9.5 mg (95%) proanthocyanidins (PCOs) per
10 mg capsule. PCOs are a special class of water soluble
bioflavonoids that are potent antioxidants. In some comparative
tests, PCOs were found to be 50 times more potent than Vitamin E
and 20 times more potent than Vitamin C. PCOs prevent the
release of histamine from mast cells. PCOs maintain capillary
strength and circulatory insufficiencies.
Each capsule contains 100 mg Grape Seed Extract (Vitis vinifera).
Standardized to yield 95% (95 mg) proanthocyanidins (PCO's).
Ingredients: Grape Seed Extract, Rice Powder.
As a dietary supplement, give two capsules per 100 lbs of body weight for 7-10
days, then give one capsule per 100 lbs of body weight daily for maintenance. Give
orally or break capsule open and mix with food. For feedings of more than one
capsule, divide between AM and PM for maintenance.
Grape Seed Extract-100Oxygen, oxidants, and antioxidants in wound healing: an emerging
Disrupted vasculature and high energy-demand by regenerating tissue results in wound hypoxia.
Wound repair may be facilitated by oxygen therapy. Evidence supporting the mode of action of
hyperbaric oxygen in promoting wound healing is sketchy, however. Topical oxygen therapy
involves local administration of pure oxygen. The advantages of topical oxygen therapy include
low cost, the lack of systemic oxygen toxicity, and possibility of home treatment. While this
modality of wound care is of outstanding interest, it clearly lacks the support of
mechanism-oriented studies. The search for mechanisms by which oxygen supports wound
healing has now taken another step. Respiratory burst-derived oxidants support healing. Oxidants
serve as cellular messengers to promote healing. Although this information is of outstanding
significance to the practice of oxygen therapy, it remains largely unexplored. The search for
"natural remedies" has drawn attention to herbals. Proanthocyanidins or condensed tannins are a
group of biologically active polyphenolic bioflavonoids that are synthesized by many plants.
Proanthocyanidins and other tannins facilitate wound healing. A combination of grape seed
proanthocyanidin extract and resveratrol facilitates inducible VEGF expression, a key element
supporting wound angiogenesis. Strategies to manipulate the redox environment in the wound are
likely to be of outstanding significance in wound healing.
: Pharmacology 2002 Jul;65(3):170-4
Protective Effect of Resveratrol against
Pentylenetetrazole-Induced Seizures and Its Modulation by an
Gupta YK, Chaudhary G, Srivastava AK.
Neuropharmacology Laboratory, Department of Pharmacology,
Institute of Medical Sciences, New Delhi, India.
The effect of trans-resveratrol (resveratrol), a polyphenolic compound with
potent antioxidant activity, was investigated against pentylenetetrazole (PTZ)
induced seizures in rats. Resveratrol (20, 40, and 80 mg/kg i.p.) administered
20 min prior to convulsive challenge with PTZ (60 mg/kg i.p.) dose
dependently reduced the percent incidence of generalized tonic-clonic
convulsions. Resveratrol (40 mg/kg) also potentiated the effect of sodium
valproate (150 mg/kg) and diazepam (2 mg/kg) against PTZ-induced seizures.
Since adenosine, an endogenous anticonvulsant, has been demonstrated to
modulate the action of various antiepileptics, experiments were also carried
out to determine whether an adenosinergic mechanism is involved in the
anticonvulsant action of resveratrol. When a subanticonvulsant dose of
adenosine (500 mg/kg) was administered together with resveratrol, a
significant reduction in the percent incidence of generalized tonic-clonic
convulsions was observed. Moreover, the nonspecific adenosine receptor
antagonist theophylline (50 mg/kg i.p.) significantly reversed the
resveratrol-induced protection, whereas the specific adenosine A(2) receptor
antagonist 3,7-dimethyl-1-propargylxanthine (1 mg/kg i.p.) could not reverse
the resveratrol-induced protection. The findings of the present study suggest
an antiepileptic potential of resveratrol and that an adenosinergic mechanism
may play a role in its anticonvulsant activity.
Bioflavonoids: proanthocyanidins and quercetin and their potential roles
in treating musculoskeletal conditions.
As a clinician treating musculoskeletal conditions, one is continually in search of safe and more
effective treatment methods that will hasten tissue healing. Chronic inflammation has been shown
to cause connective tissue degradation. Typically, nonsteroidal anti-inflammatory drugs
(NSAIDs) and/or corticosteroids are used to control the inflammatory process, however,
long-term use has been associated with potentially serious side effects. The purpose of this article
is to introduce and describe literature on 2 natural compounds, namely, proanthocyanidin (PCO)
and quercetin, which are 2 specific types of bioflavonoids, and to discuss their potential benefits
in treating musculoskeletal conditions. There is evidence to suggest that flavonoids may be
beneficial to connective tissue for several reasons, which include the limiting of inflammation and
associated tissue degradation, the improvement of local circulation, as well as the promoting of a
strong collagen matrix. An overview of bioflavonoids as well as relevant research, safety issues,
absorption, and specific sources of PCO and quercetin in foods and through supplementation is
Cellular protection with proanthocyanidins derived from grape seeds.
These results demonstrate that GSPE is
highly bioavailable and may serve as a potential therapeutic tool in protecting multiple target
organs from structurally diverse drug- and chemical-induced toxicity.
natural sources of resveratrol besides grapes
"One of the richest sources of resveratrol is the weed Polygon urn cuspidaturn, the root
extract of which has been used in Asian countries to treat headaches, amenorrhea,
dysentery, microbial and viral infections, inflammatory and allergic responses, asthma,
arthritis, hepatitis, trauma, hyperlipidemia and arteriosclerosis, hypertension, and
cancer.The root extracts of Polygonurn cuspidaturn, known as Hu-Chang and Ko-jo-kon,
have been credited with many phytotherapeutic successes in Japanese and Chinese
Inhibition of cancer growth by resveratrol is related to its low
The relationship between resveratrol (RES) bioavalability and its effect on tumor growth was
investigated. Tissue levels of RES were studied after i.v. and oral administration of
trans-resveratrol (t-RES) to rabbits, rats, and mice. Half-life of RES in plasma, after i.v.
administration of 20 mg t-RES/kg b.wt., was very short (e.g., 14.4 min in rabbits). The highest
concentration of RES in plasma, either after i.v. or oral administration (e.g., 2.6 +/- 1.0 &mgr;M
in mice 2.5 min after receiving 20 mg t-RES/kg orally), was reached within the first 5 min in all
animals studied. Extravascular levels (brain, lung, liver, and kidney) of RES, which paralleled
those in plasma, were always < 1 nmol/g fresh tissue. RES measured in plasma or tissues was in
the trans form (at least 99%). Hepatocytes metabolized t-RES in a dose-dependent fashion (e.g.,
43 nmol of t-RES/g x min in the presence of 20 &mgr;M tRES), which means that the liver can
remove circulating RES very rapidly. In vitro B16 melanoma (B16M) cell proliferation and
generation of reactive oxygen species (ROS) was inhibited by t-RES in a
concentration-dependent fashion (100% inhibition of tumor growth was found in the presence of
5 &mgr;M t-RES). Addition of 10 &mgr;M H(2)O(2) to B16M cells, cultured in the presence of
5 &mgr;M t-RES, reactivated cell growth. Oral administration of t-RES (20 mg/kg twice per
day; or included in the drinking water at 23 mg/l) did not inhibit growth of B16M inoculated into
the footpad of mice (solid growth). However, oral administration of t-RES (as above) decreased
hepatic metastatic invasion of B16M cells inoculated intrasplenically. The antimetastatic
mechanism involves a t-RES (1 &mgr;M)-induced inhibition of vascular adhesion molecule 1
(VCAM-1) expression in the hepatic sinusoidal endothelium (HSE), which consequently
decreased in vitro B16M cell adhesion to the endothelium via very late activation antigen 4
Resveratrol, a chemopreventive agent, disrupts the cell cycle control of
human SW480 colorectal tumor cells.
Resveratrol is a natural polyphenolic compound produced by a number of plants and found in
high amount in peanuts, seeds, grapes or berries as source of human nutrition. Epidemiological
studies strongly suggest that resveratrol may act as a cancer chemopreventive compound....In conclusion,
resveratrol exerts a strong inhibition of SW480 human colorectal tumor cell proliferation at least
by modulating cyclin and cyclin-dependent kinase activities.
Resveratrol induced serine phosphorylation of p53 causes apoptosis in a
mutant p53 prostate cancer cell line.
Albany, New York, USA.
PURPOSE: Resveratrol (Calbiochem, La Jolla, California) is a naturally occurring stilbene
reported to cause apoptosis in various cultured cancer cells..... CONCLUSIONS: Resveratrol
causes apoptosis in DU 145 prostate cancer cells. This action depends on the activation of
MAPK, increase in cellular p53 content, serine-15 phosphorylation of p53 and increased p53
binding to DNA.
Accumulating evidence demonstrates that polyphenols in natural products are beneficial against
human lethal diseases such as cancer and metastasis. The underlying mechanisms of anti-cancer
effects are complex. Recent studies show that several polyphenols, including
epigallocatechin-3-gallate (EGCG) in green tea and resveratrol in red wine, inhibit angiogenesis
when administrated orally. These polyphenols have direct effects on suppression of angiogenesis
in several standard animal angiogenesis models. Because angiogenesis is involved in many
diseases such as cancer, diabetic retinopathy and chronic inflammations, the discovery of these
polyphenols as angiogenesis inhibitors has shed light on the health beneficial mechanisms of
natural products, which are rich in these molecules. At the molecular level, recent studies have
provided important information on how these molecules inhibit endothelial cell growth. Perhaps
the greatest therapeutic advantage of these small natural molecules over large protein compounds
is that they can be administrated orally without causing severe side effects. It is anticipated that
more polyphenols in natural products will be discovered as angiogenesis inhibitors and that these
natural polyphenols could serve as leading structures in the discovery of more potent, synthetic
Cancer chemopreventive activity of resveratrol.
Cancer chemopreventive agents are designed to reduce the incidence of tumorigenesis by
intervening at one or more stages of carcinogenesis. Recently, resveratrol, a natural product
found in the diet of humans, has been shown to function as a cancer chemopreventive agent.
Resveratrol was first shown to act as an antioxidant and antimutagenic agent, thus acting as an
anti-initiation agent. Further evidence indicated that resveratrol selectively suppresses the
transcriptional activation of cytochrome P-450 1A1 and inhibits the formation of
carcinogen-induced preneoplastic lesions in a mouse mammary organ culture model. Resveratrol
also inhibits the formation of 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted mouse
skin tumors in the two-stage model. The enzymatic activities of COX-1 and -2 are inhibited by
resveratrol in cell-free models, and COX-2 mRNA and TPA-induced activation of protein
kinase C and AP-1-mediated gene expression are suppressed by resveratrol in mammary
epithelial cells. In addition, resveratrol strongly inhibits nitric oxide generation and inducible nitric
oxide synthase protein expression. NF kappa B is strongly linked to inflammatory and immune
responses and is associated with oncogenesis in certain models of cancer, and resveratrol
suppresses the induction of this transcription factor by a number of agents. The mechanism may
involve decreasing the phosphorylation and degradation of I kappa B alpha. At the cellular level,
resveratrol also induces apoptosis, cell cycle delay or a block in the G(1) --> S transition phase
in a number of cell lines. Thus, resveratrol holds great promise for future development as a
chemopreventive agent that may be useful for several disorders. Preclinical toxicity studies are
underway that should be followed by human clinical trials.
Estrogenic and antiestrogenic properties of resveratrol in mammary tumor
Therefore, in the absence of E2, resveratrol exerts mixed estrogen agonist/antagonist activities in
some mammary cancer cell lines, but in the presence of E2, resveratrol functions as an
antiestrogen. In rodent models, carcinogen-induced preneoplastic lesions and mammary tumors
are inhibited. These data suggest that resveratrol may have beneficial effects if used as a
chemopreventive agent for breast cancer.
Resveratrol induces apoptosis in thyroid cancer cell lines via a MAPK- and
Two papillary thyroid carcinoma (PTC) and two follicular thyroid carcinoma (FTC) cell lines
treated with resveratrol (RV), 1-10 microM, showed activation and nuclear translocation of
MAPK (extracellular signal-regulated kinase 1/2). Cellular abundance of the oncogene
suppressor protein p53, serine phosphorylation of p53, and abundance of c-fos, c-jun, and p21
mRNAs were also increased by RV. Inhibition of the MAPK pathway by either H-ras antisense
transfection or PD 98059, an MAPK kinase inhibitor, blocked these RV-induced effects.
Addition of pifithrin-alpha, a specific inhibitor of p53, or transfection of p53 antisense
oligonucleotides caused decreased RV-induced p53 and p21 expression in PTC and FTC cells.
Studies of nucleosome levels estimated by ELISA and of DNA fragmentation showed that RV
induced apoptosis in both papillary and follicular thyroid cancer cell lines; these effects were
inhibited by pifithrin-alpha and by p53 antisense oligonucleotide transfection. PD 98059 and
H-ras antisense transfection also blocked induction of apoptosis by RV. Thus, RV acts via a
Ras-MAPK kinase-MAPK signal transduction pathway to increase p53 expression, serine
phosphorylation of p53, and p53-dependent apoptosis in PTC and FTC cell lines.