Description

Medicinal Parts

The medicinal parts are the leaves, the fruit, and the juice.

Flower and Fruit

The flowers are in compound compact panicles. The petals are about 5 mm long and droop like the sepals. The fruit is oblong to globular, 6 to 22 mm long, dark blue-violet, red, green or yellow, juicy, sweet or sour. The seeds are pear-shaped, with hard skin and two long dimples on the side.

Leaves, Stem, and Root

The vine is a 30-cm high climber with deep, heavily branched roots and a woody trunk. The trunk has striped, loose bark. The brown-red to brown-yellow branches are glabrous or slightly downy and finely grooved. The leaves are orbicular, generally in 3 to 5 lobes or blades. They are deeply notched at the stem. The upper surface of the leaves is glabrous, the under surface is lanate.

Habitat

The plant is indigenous to southern Europe and western Asia and is cultivated today in all temperate regions of the world.

Production

Vine leaves are the foliage leaves of Vitis vinifera.

Actions & Pharmacology

Compounds

Flavonoids (4 to 5%): including, kaempferol-3-O-glucosides, quercetin-3-O-glucosides

Tannins: procyanidolic oligomers (proanthocyanidins), including constituent monomers of catechin epicatechin

Non-flavonoids (Stilbenes): resveratrol and viniferins

Fruit acids: including, tartaric acid, malic acid, succinic acid, citric acid, oxalic acid

Phenylacrylic acid derivatives: p-cumaroyl acid, caffeoyl acid, feruloylsuccinic acid

Effects

Grape Seed extract has shown positive effects against peripheral venous insufficiency, as an antioxidant, in varicose veins, capillary fragility, disorders of the retina including diabetic retinopathy, edema, ocular stress, and premenstrual syndrome. In vitro and animal trials have demonstrated antioxidant, vascular, cytotoxic, chemopreventive, and cytoprotective effects. In addition, the excellent antioxidant effects of Grape Seed extract may offer protection against atherosclerosis and other chronic degenerative diseases, such as cancer. Grape Seed extract may also support collagen stabilization. Results of an in vitro study demonstrated that procyanidins (from Vitis vinifera seeds) are highly effective scavengers of hydrophilic and lipophilic radicals. Procyanidins exhibited remarkable, dose-dependent, anti-lipoperoxidant activity. Furthermore, they can protect liposomal membranes from lipid peroxidation through a radical scavenging action and by a chelation mechanism (Facino et al, 1994).

Antiatherosclerotic Effects

The oxidation of low-density lipoproteins (LDL) by free radicals is associated with the initiation of atherosclerosis. Proanthocyanidin decreases the number of LDL-positive macrophage-derived foam cells in atherosclerotic lesions. The compound also inhibits the oxidation of cholesteryl linoleate in LDL to exert a reduction in atherosclerosis of the aorta (Nuttall, 1998, Yamakoshi, 1999).

Anticarcinogenic/Antitumor Effects

Chemoprotective properties of proanthocyanidins include activity against free radicals and oxidative stress (Ye, 1999). The antitumor-promoting activity due to strong antioxidant effects of the compound has been demonstrated in animal models (Zhao, 1999).

Antioxidant Effects

Proanthocyanidin from Grape Seed extract exerts a concentration-dependent inhibition of oxygen free radicals. In one study, the antioxidant effect of proanthocyanidin was more potent compared to vitamin C and vitamin E succinate (Bagchi, 1999, 1997). The compound also inhibits peroxidation of phosphatidylcholine liposomes (Plumb, 1998). In one study, Grape Seed extract trapped free radicals and inhibited their production, markedly delayed the onset of lipid peroxidation, and inhibited the damaging effects of the enzymes that can degrade connective tissue structures. The antioxidant activity of PCOs from Grape Seed extract were much greater (approximately 50 times) than that of vitamin C and vitamin E, providing a strong rationale for using these compounds in the therapeutic management of microvascular disorders (Facino et al, 1994).

Another in vitro study demonstrated a protective effect of Grape Seed proanthocyanidins against peroxidation of polyunsaturated fatty acids (PUFA) by UV-C irradiation (Bouhamidi et al, 1998). Mice fed Grape Seed proanthocyanidin extract (GSPE) had a decrease in 12-O-tetradecanoylphorbol-13-acetate (TPA) induced production of reactive oxygen species, DNA fragmentation in hepatic and brain tissues and lipid peroxidation. GSPE was a better scavenger of free radicals and inhibitor of oxidative tissue damage than vitamin C, vitamin E succinate, or a combination of these vitamins and beta-carotene in the doses studied (Bagchi et al, 1998).]

Cardioprotective Effects

Dietary polyphenols from Grapes have multiple cardio-protective properties that were initially described through the “French Paradox,” in which it was observed that despite a diet high in saturated fat, people who regularly consume red wine are also less likely to develop coronary heart disease. Recent research demonstrates that this effect may be due not only to possible inhibitory effects of polyphenols on LDL oxidation, but to other effects as well: the action of the Grape polyphenols on altering hepatic cholesterol absorption, effects on triglyceride assembly and secretion, and changes in the processing of lipoproteins in plasma. Both in vitro and in vivo models have shown these positive cardio-protective effects on lipid metabolism and inflammation (Zern, 2005).

Collagen Stabilization

Procyanidolic oligomers effectively caused cross-linking in collagen in vitro. An in vitro study determined that procyanidins inhibit the activities of some proteolytic enzymes (collagenase, elastase) involved in the degradation of the main structural components of the extravascular matrix, collagen, elastin, and hyaluronic acid (Facino et al, 1994).

Cytotoxic Effects

One study reported a Grape Seed extract exhibited cytotoxicity toward some cancer cells (Joshi et al, 1998). An abstract reported that Grape Seed extract exerted a chemopreventive effect on adenomas polyposis coli gene mutation-associated intestinal adenoma formation. Tumor multiplicity was significantly reduced (p<0.01) from a mean of 78.3 in control mice to 43.5 in mice fed Grape Seed extract. The number of small polyps was also significantly reduced in the Grape Seed extract group (p value not indicated) (Arii et al, 1998).

Cytoprotective Effects

Various abstracts reported that Grape Seed extract has in vitro effects that may ameliorate the toxic effects of chemotherapeutic agents (Joshi et al, 1998); that it provides some protection against radiation damage to spermatogonial cells in the testes (Lanka et al, 1998); and that it may attenuate acetaminophen induced hepatic DNA damage, apoptopic cell death, and influence gene expression (Ray et al, 1998). Grape Seed extract inhibited stomach mucosal injury in mice induced by 60 percent ethanol (EtOH) containing 150 millimolar hydrochloric acid (HCl) (Saito et al, 1998).

Hair Growth

Proanthocyanidins extracted from Grape Seeds promote proliferation of hair follicle cells, and possess hair-cycle converting activity from the telogen phase to the anagen phase. Epicatechin and catechin are the constitutive monomers inducing the degree of polymerization inducing hair growth (Takahashi, 1998).

Hepatoprotective Effects

Proanthocyanidin has been shown to significantly attenuate acetaminophen-induced hepatic DNA damage, apoptopic and necrotic cell death of liver cells. The component also antagonizes acetaminophen induced changes in bcl-X1 expression (Ray, 1999).

Ischemia Preventive Effects

Maintenance of microvascular injury by procyanidins occurs through the scavenger effect of reactive oxygen species (Maffei Facino, 1994). Procyanidins also reduce ventricular contraction in a dose-dependent fashion. Procyandins decrease coronary perfusion pressure and improve cardiac mechanical performance. (Maffei Facino R, 1996).

Ocular Stress

Grape Seed extract may improve resistance to glare, recovery from exposure to bright light, night vision, and ocular stress. In a 90-day double-blind study in 75 patients with ocular stress caused by their activity in front of a computer screen, Grape Seed extract (300 mg/day) was shown to significantly improve objective (contrast sensitivity) and subjective symptoms of eye strain (Bombardelli & Morazzoni, 1995).

Premenstrual Syndrome

Administration of Grape Seed extract may be beneficial in treating symptoms of premenstrual syndrome. Concomitant use of Grape Seed extract may decrease some of the negative side effects of hormone therapy in women (Henriet, 1993).

Vascular Effects

An abstract reported polymeric phenolic compounds found in Grape Seed extracts to have effects on vascular tone in vitro, which are unlikely associated with antioxidant activity (Karim et al, 1998). PCOs reduced the incidence of atherosclerotic lesions in rabbits fed a high-cholesterol diet. After 8 weeks on a high-cholesterol diet, rabbits fed procyanidins did not exhibit the increased aortic plaque that the other experimental group did (Sevanian, 1998). PCOs also protect against free radical damage with their potent antioxidant and free radical scavenging action; and inhibit enzymatic cleavage of collagen by enzymes secreted by leukocytes during inflammation and microbes during infection (Facino et al, 1994; Meunier et al, 1989).

Procyanidins isolated from Grape Seed stabilizes capillary walls and prevents increases in permeability that inhibits edema (Robert, 1990; Zafirov, 1990). Overproduction of hyaluronan content associated with pathologic venous walls, in particular vein-lymphatic edema, is decreased by procyanidolic oligomers (Drubaix, 1997). Procyanidolic oligomers cross-link collagen fibers, resulting in reinforcement of the natural cross-linking of collagen that forms the collagen matrix of vascular connective tissue (Tixier et al, 1984). The vascular activity of procyanidin has positive effects on diabetic retinopathy, night vision and ocular stress (Boissin, 1988; Corbe, 1988; Soyeux, 1987).

Clinical Trials

Breast Induration

The efficacy of IH636 Grape seed proanthocyanadin extract (GSPE) for breast induration (tissue hardening) following radiation therapy was tested in a randomized, double-blind, placebo-controlled study of 66 patients with the condition after undergoing high-dose radiotherapy for early breast cancer. Participants, who reported moderate or marked breast induration at a mean 10.8 years since radiotherapy, were randomly assigned to active drug (n=44) or placebo treatment (n=22). All patients were given GSPE 100 mg, 3 times a day orally, or corresponding placebo capsules, for 6 months. No significant differences between the two treatment groups were found in terms of external assessments of tissue hardness or breast appearance, or patient self-assessments of breast hardness, pain, or tenderness (Brooker et al, 2006).

Coronary Artery Disease

A number of lifestyle modifications are likely beneficial for women after menopause to compensate for the loss of estrogen—which has profound effects in increasing lipids and other risk factors for coronary heart disease. In this single-blind, crossover trial, Grape polyphenols delivered in the form of lypholized grape powder (LGP) was shown to have a number of key significant cardio-protective effects in both pre- and postmenopausal women. Twenty women were randomly assigned to consume 36 g of the LGP or a placebo for 4 weeks. After a 3-week washout period, the subjects were assigned to a different treatment for 4 weeks. A number of beneficial effects on plasma lipids were observed. After taking LGP, plasma triglyceride concentrations were reduced by 15% in pre-menopausal women and by 6% in post-menopausal women (P<0.01). Plasma LDL cholesterol and apolipoproteins B and E also were significantly lower (P<0.05). Whole-body oxidative stress was significantly reduced, and markers of inflammation were likewise lowered (Zern 2005).

Antioxidant

In a double-blind, placebo-controlled study researchers sought to determine the antioxidant effects of PCO Phytosome® in 20 young volunteers. The Phytosome process binds one part of the Grape Seed PCO extract with two parts of phosphatidylcholine. The result is a completely new molecule composed of a central molecule of PCO encased by two phosphatidylcholine molecules. Subjects were given 2 capsules containing 300 mg of PCO Phytosome or a placebo for 5 days. Blood samples were taken at the start of the study and at the end of the study and assayed for antioxidant activity as well as vitamins C and E levels. After a washout period of at least 2 weeks, the study was crossed over. While the PCO Phytosome had no effect on serum vitamins C and E levels, it increased the serum total antioxidant activity (TAC) considerably. On day 5, TAC increased from 408 to 453 μmol/l trolox equivalents one hour after dosage (Nutall et al, 1998).

Energy Intake

A randomized, double-blind, placebo-controlled crossover study of 51 normal to overweight subjects found Grape seed extract effective in reducing 24-hour energy intake (EI) in certain individuals. For 3 days, subjects ate an ad libitum lunch and dinner. Standard breakfast and snacks were provided. Supplements were taken 30-60 minutes prior to each meal. In the total study population, no differences in 24-hour energy intake were found between the two treatment groups. However, in the subgroup of 23 subjects with an energy requirement greater than or equal to the median of 7.5 MJ/day, EI was reduced by 4% (p=0.05) while taking Grape seed extract compared to placebo. The extract had no effects on satiety, mood, or tolerance (Vogels et al, 2004).

Edema

The efficacy of Grape Seed extract (Endotelon) was evaluated in 165 women suffering from edema due to premenstrual syndrome. The multicenter, open study included women ages 18-50 years. Each woman received 4 tablets Grape Seed extract per day (exact dose not mentioned) from day 14 through day 28 of their menstrual cycle, for a total of 4 cycles. Mammary symptoms, abdominal swelling, pelvic pains, weight variations, and venous problems of the legs disappeared or improved in 60.8% of the cases after 2 cycles of treatment and in 78.8% of the cases after 4 cycles of treatment (Amsellem et al, 1987).

The effect of PCO from Grape Seed extract was shown to have protective effects on the postoperative edema compared to placebo in a double-blind, placebo-controlled study. Thirty-two female patients undergoing a facelift were administered either 300 mg Grape Seed extract or placebo daily over the 5 days preceding the operation, and postoperatively from days 2 to 6. Prophylactic decrease in postoperative facial edema was the main efficacy criteria. The Grape Seed extract cohort scored significantly better than placebo against postoperative facial swelling (Baruch, 1984).

Pancreatitis

Three patients with chronic pancreatitis (2 with history of alcohol excess and 1 idiopathic) experienced a decrease in frequency and intensity of abdominal pain and resolution of vomiting (in 1 patient) when taking Grape Seed proanthocyanidin extract ActiVin®, a potent antioxidant. Medical treatments had failed in all patients while invasive procedures were either not indicated or were refused by the patients. ActiVin 200 mg daily orally provided some symptom relief while 300 mg daily was used when there was a worsening of symptoms. ActiVin was well tolerated and may be useful in the management of chronic or relapsing pancreatitis (Banerjee & Bagchi, 2001).

Peripheral Venous Insufficiency

The efficacy of Grape Seed extract was evaluated for the treatment of venous insufficiency and symptoms due to hormonal supplementation. Grape Seed extract (150 mg twice daily) was administered to 4,729 patients in an open-label study. Peripheral venous insufficiency was evaluated 45 and 90 days after treatment. The efficacy score was based on symptoms of nocturnal cramps, paresthesias, sensation of warmth, cyanosis, and edema. The sensation of heaviness in the legs decreased in 57% of cases by day 45 and 89.4% by day 90. In addition, the improvement of symptoms occurred in 66% of cases by day 45 and 79-83% of cases by day 90 (Henriet, 1993).

Vision Improvement

A lower resistance to glare and alteration of scotopic vision are associated with retinal pathology related to age, fatigue, and stress. The effect of procyanidolic oligomers (PCO) on light vision and chorioretinal circulation was determined in 100 subjects. PCO (Endotelon®) was administered in tablets of 50 mg 4 times daily for 5 weeks. Improvements in visual adaptation to low luminance and visual performances after glare, as measured by a nyctometer, were significant (Boissin et al, 1988; Corbe et al, 1988).

Indications & Usage

Unproven Uses

In Folk medicine, Grape preparations are used in venous diseases and blood circulation disorders.

Indian Medicine

Grape is used for headache, dysuria, scabies, skin diseases, gonorrhea, hemorrhoids, and vomiting.

Precautions & Adverse Reactions

No health hazards or side effects are known in conjunction with the proper administration of designated therapeutic dosages. A reversible inhibition of intestinal enzyme activity (alkaline phosphatase, sucrase and dipeptidyl peptidase) was demonstrated in animal models (Tebib, 1994).

Drug Interactions

No human interaction data available.

Dosage

How Supplied

• Capsule—25 mg, 30 mg, 50 mg, 60 mg, 500 mg
• Tablet—50 mg

Daily Dosage

Grape Seed extract has been used for preventive therapy with 50 mg daily and treatment doses of 150 to 600 mg daily in divided doses (Arne, 1982; Baruch, 1984; Corbe; 1988; Delacroix, 1981; Henriet, 1993; Nuttall, 1998; Soyeux, 1987).

Literature