Proanthocyanidin-rich Extract Research Articles

Apple Proanthocyanidins Do Not Reduce the Induction of Preneoplastic Lesions in the Colon of Rats Associated with Human Microbiota

Since the gut microbiota metabolizes various dietary constituents unabsorbed by the small intestine and modulates colon function, it plays an essential role in colon carcinogenesis. First, we have developed a model of human microbiota-associated rats (HMA), fed a human-type diet and injected with 1-2,dimethylhydrazine (DMH). We observed that the number and size of DMH-induced aberrant crypt foci (ACF) were significantly higher in HMA rats than in germ-free or conventional rats. Second, we used this model to assess the protective effect of an apple proanthocyanidin-rich extract (APE) on colon carcinogenesis. In this model, ACF number and multiplicity were not reduced by APE at 0.001% and 0.01% in drinking water. They were higher with APE 0.1% than with APE 0.01%. Therefore, the cross-talk between human microbiota and the colon epithelium should be taken into account in carcinogenesis models. Moreover, attention should be paid prior to using proanthocyanidin extracts as dietary supplements for humans.

Antioxidant, antiacetylcholinesterase and antimicrobial activities of Cymbopogon schoenanthus L. Spreng (lemon grass) from Tunisia

Aqueous extract, proanthocyanidin rich extract, and organic extracts of Cymbopogon schoenanthus L. Spreng (lemon grass) shoots from three different locations in South Tunisia were screened for their antioxidant, acetylcholinesterase and antimicrobial activities. In addition to the evaluation of these activities, the contents of flavonoids and total phenolic compounds were determined. Antioxidant activity measured by DPPH assay showed that the proanthocyanidin extract exhibited higher antioxidant activity than the aqueous extract. Extract concentration providing 50% inhibition (IC 50) ranged from 16.4 ± 6.8 μg/mL to 26.4 ± 6.8 μg/mL. The antioxidant activity was also determined using the β-carotene/linoleic acid bleaching test. The best results (IC 50 = 0.11 ± 0.10 mg/mL) were obtained with the proanthocyanidin extract of the plants collected from the desert region (Dhibat). The greatest acetylcholinesterase inhibitory activity (IC 50 = 0.23 ± 0.04 mg/mL) was exhibited by the ethyl acetate and methanol extracts of the plants collected from the mountainous region. It seems that extracts obtained with more polar solvents gave better results. The proanthocyanidin extracts showed a good antimicrobial activity against Streptococcus sobrinus at low concentration (MIC = 4 mg/mL). Therefore, these extracts could be used to prevent carious lesions by inhibiting S. sobrinus growth.

Effect of a Proanthocyanidin-Rich Extract from Longan Flower on Markers of Metabolic Syndrome in Fructose-Fed Rats

Recent evidence strongly suggests that oxidative stress due to redox imbalance is highly associated with metabolic syndrome. The objective of this study was to evaluate the effect of the supplementation of longan flower water extract (LFWE), which showed powerful antioxidative activity in vitro, on markers of metabolic syndrome in a fructose-fed rat model. Male Sprague-Dawley rats were randomly divided into four groups: group C, fed with standard Purina chow; group F, fed with high-fructose diet (HF) alone; group L, fed with HF plus LFWE 125 mg/kg bw per day by gavage; and group H, fed HF plus LFWE 250 mg/kg bw per day by gavage. The dietary manipulation lasted for 14 weeks. Results of our study showed that rats fed with HF resulted in oxidative stress and affected the antioxidant status including plasma thiobarbituric acid and liver antioxidant enzyme activity. Treatment with LFWE significantly augmented the antioxidant system. HF was able to cause insulin resistance and elevation of the blood pressure. The supplementation of LFWE ameliorated insulin resistance by enhancing the expression of insulin signaling pathway related proteins, including insulin receptor substrate-1 and glucose transporter 4. LFWE supplementation was also found to decrease systolic blood pressure. These findings indicate that longan flower water extract may improve the symptoms of metabolic syndrome in fructose-fed rats.

Cranberry Proanthocyanidins Induce Apoptosis and Inhibit Acid-Induced Proliferation of Human Esophageal Adenocarcinoma Cells

The occurrence of esophageal adenocarcinoma and its only recognized precursor lesion, Barrett's esophagus, has rapidly increased during the past three decades. The precise reason for the rise remains to be elucidated, but increasing rates have been linked to multiple nutritional factors. Plant-based diets have generally been associated with a reduction of risk for esophageal adenocarcinoma and those of animal origin with risk escalation. Moreover, a number of recent in vitro and limited in vivo investigations have reported that cranberry extracts affect multiple cancer-associated processes in breast, colon, prostate, and other cancer cell lines of epithelial origin. Thus, this study sought to investigate the chemopreventive potential of a cranberry proanthocyanidin rich extract (PAC) in SEG-1 human esophageal adenocarcinoma (EAC) cells. PAC pretreatment significantly inhibited the viability and proliferation of EAC cells in a time- and dose-dependent manner. Moreover, PAC (50 microg/mL) significantly inhibited acid-induced cell proliferation of SEG-1 cells. PAC treatment induced cell cycle arrest at the G1 checkpoint and significantly reduced the percentage of SEG-1 cells in S-phase following 24 and 48 h of exposure. PAC treatment also resulted in significant induction of apoptosis. Thus, PAC modulates cell cycle regulation, aberrant proliferation, and apoptosis, all key biological processes altered during progression to esophageal adenocarcinoma. These findings support that further mechanistic studies are warranted to more fully elucidate the inhibitory potential of PAC against esophageal cancer.

Effect of dietary fat-soluble vitamins A and E and proanthocyanidin-rich extract from grape seeds on oxidative DNA damage in rats

This study reports the effect of the fat-soluble vitamin A or vitamin E and grape seed proanthocyanidin extract (GSPE) on oxidative DNA damage estimated by 8-oxo-7, 8-dihydro-2′-deoxyguanosine (8-oxodG) contents in urine and leukocyte of rats. Little is known about the antioxidant potency of dietary anthocyanidins and consequently, the aim of this study was to establish whether anthocyanidins could act as putative antioxidant micronutrients. Seven groups of male Sprague-Dawley rats were fed during 47 days with the following diets: a basic diet, two deficient vitamin A or E diets, two supplemented vitamin A or E diets and two supplemented diets enriched with two doses of grape seed proanthocyanidin extract. At the end of the diet intervention period, 24 h, urine and blood were collected. The levels of 8-oxodG in leukocytes rats were significantly lower in the supplemented vitamin A, E and GSPE diet groups with respect to the control group. However, consumption of α-tocopherol, vitamin A or GSPE had no effect on the excretion of the oxidised nucleoside 8-oxodG. These results suggest that a vitamin E and A and GSPE enriched-diets have a protective effect on oxidative DNA damage limited to rat leukocytes.

Attenuation of Renal Ischemia-Reperfusion Injury by Proanthocyanidin-Rich Extract from Grape Seeds

The effects of proanthocyanidin-rich extract in rats subjected to renal ischemia-reperfusion were examined. Proanthocyanidin-rich extract, which is prepared from grape seeds (Vitis vinifera L.), was given orally at doses of 5 and 10 mg/kg body weight/d for 20 consecutive days prior to ischemia-reperfusion. Administration of proanthocyanidin-rich extract attenuated renal dysfunction, as indicated by serum urea nitrogen and creatinine levels. Additionally, in the ischemic-reperfused kidneys, increased levels of thiobarbituric acid (TBA)-reactive substance and alterations of antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase (GSH-Px) were observed. Proanthocyanidin-rich extract-treated groups showed significantly reduced renal TBA-reactive substance levels and enhanced catalase and GSH-Px activities. These results suggest that proanthocyanidin-rich extract has protective effects against ischemia-reperfusion-induced renal damage associated with oxidative stress.

Antioxidant activity of a proanthocyanidin-rich extract from grape seed in whey protein isolate stabilized algae oil-in-water emulsions.

Algae oil-in-water emulsions stabilized with 0.2% whey protein isolate (WPI) at pH 3.0 and 7.0 were chosen to evaluate antioxidant activity of a proanthocyanidin-rich extract from grape seed. In this emulsion system, (+)-catechin and ascorbic acid (620 microM) were found to be prooxidative at pH 3.0 and ineffective at pH 7.0. Grape seed extract was not able to effectively inhibit both lipid hydroperoxides and propanal formation when added to the emulsion at 124 microM. However, increasing the concentration of the grape seed extract to 620 microM resulted in inhibition of both lipid hydroperoxide and propanal formation at pH 3.0 and 7.0. None of the antioxidants tested had any effect on the physical stability of the WPI-stabilized emulsion. The superior antioxidant activity of the grape seed extract is likely due to the presence of oligomeric procyanidins which are better antioxidants compared to their monomeric counterparts.

Grape seed proanthocyanidins improved cardiac recovery during reperfusion after ischemia in isolated rat hearts

Increasing evidence shows that red wine consumption has cardioprotective effects. These effects have been attributed to the polyphenolic compounds in grapes. We studied the effects of red grape seed proanthocyanidins on the recovery of postischemic function in isolated rat hearts. Two groups of rats were fed different doses of proanthocyanidin-rich extract for 3 wk and another group was untreated and served as controls. The animals were then anesthetized and the hearts were isolated and subjected to 30 min of ischemia followed by 2 h of reperfusion. Coronary effluents were collected during the third minute of reperfusion for measurement of oxygen free radicals by using electron spin resonance spectroscopy. In rats treated with 50 and 100 mg grape seed proanthocyanidins/kg, the incidence of reperfusion-induced ventricular fibrillation was reduced from its control value of 92% to 42% and 25%, respectively (P < 0.05 for both). The incidence of ventricular tachycardia showed the same pattern. In rats treated with 100 mg proanthocyanidins/kg, the recovery of coronary flow, aortic flow, and developed pressure after 60 min of reperfusion was improved by 32% +/- 8%, 98% +/- 8%, and 37% +/- 3%, respectively (P < 0.05 for all) compared with untreated control rats. Electron spin resonance studies indicated that proanthocyanidins significantly inhibited the formation of oxygen free radicals. In rats treated with 100 mg proanthocyanidins/kg, free radical intensity was reduced by 75% +/- 7% (P < 0.05) compared with the control rats. Grape seed proanthocyanidins have cardioprotective effects against reperfusion-induced injury via their ability to reduce or remove, directly or indirectly, free radicals in myocardium that is reperfused after ischemia.

Safety evaluation of proanthocyanidin-rich extract from grape seeds

Proanthocyanidins, extracted from grape seeds, are widely used mainly as nutritional supplements. However, there has not been a systematic report to investigate toxicological studies on proanthocyanidins, especially in oral administration. In our studies, proanthocyanidin-rich extract from grape seeds was subjected to a series of toxicological tests to document its safety for use in various foods. The grape seed extract (GSE) was examined for acute and subchronic oral toxicity using Fischer 344 rats and for mutagenic potential by the reverse mutation test using Salmonella typhimurium, the chromosomal aberration test using CHL cells, and the micronucleus test using ddY mice. No evidence of acute oral toxicity at dosages of 2 and 4 g/kg, and no evidence of mutagenicity in the above tests was found. Administration of GSE as a dietary admixture at levels of 0.02, 0.2 and 2% (w/w) to the rats for 90 days did not induce noticeable signs of toxicity. The no-observed-adverse-effect level (NOAEL) of GSE in the subchronic toxicity study was 2% in the diet (equal to 1410 mg/kg body weight/day in males and 1501 mg/kg body weight/day in females). The results of our studies indicate a lack of toxicity and support the use of proanthocyanidin-rich extract from grape seeds for various foods.

Effect of Proanthocyanidin-Rich Extract from Grape Seeds on Human Fecal Flora and Fecal Odor

The aim of this study was to evaluate the effects of proanthocyanidin-rich extracts from grape seeds on human fecal  ora and fecal odor. Proanthocyanidin-rich extract containing 38.5% proanthocyanidin was administered to nine healthy adults at a dose of 0.5 g/day (0.19 g/day as proanthocyanidin) for 2 weeks, and proanthocyanidin-rich extract containing 89.3% proanthocyanidin was administered to eight elderly inpatients at a dose of 0.43 g/day (0.38 g/day as proanthocyanidin) for 2 weeks. Green tea extract and/or champignon extract, both of which have been found to have a deodorant effect on fecal odor, were administered in a similar manner as controls. In healthy adults, marked decreases in fecal odor and concentrations of methyl mercaptan and hydrogen sul. de in feces were observed during proanthocyanidin-rich extract intake, but the effects of green tea extract and champignon extract were weak. After 2 weeks of proanthocyanidin-rich extract intake, the number of Bifidobacterium had increased significantly (p<0.05), whereas the number of Enterobacteriaceae tended to decrease ( p =0.121). The level of putrefactive substances, including ammonia, phenol, p -cresol, 4-ethylphenol, indole, and skatols tended to decrease after proanthocyanidin-rich extract intake, and fecal pH also tended to decrease. Nurses and hospital aides performed organoleptic evaluations that showed less fecal odor in elderly inpatients with proanthocyanidin-rich extract intake than with champignon extract intake. In an in vitro study, the proanthocyanidin-rich extract reduced methyl mercaptan and hydrogen sul. de release from the feces of healthy adults, and also reduced methyl mercaptan release from methyl mercaptan solution. The absorptive ability of methyl mercaptan was stronger in procyanidin oligomers larger than decamer than procyanidin dimer to tetramer. These results suggest that proanthocyanidin-rich extract from grape seed intake induces a reduction in the level of putrefactive products in the intestine, which may be linked to the modest change in the numbers of Bifidobacterium and Enterobacteriaceae . They also suggest that the strong deodorant effect of proanthocyanidins on fecal odor is due to the decrease of putrefactive products and the absorption of malodorous compounds from feces by the larger molecular procyanidin oligomers in the proanthocyanidins. Keywords : proanthocyanidin, grape seed extract, polyphenol, fecal  ora, fecal odor.

ブドウ種子抽出物のラジカル捕捉能に及ぼす熱およびｐＨの影響とこんにゃくの製造

プロアントシアニジンが主成分であるブドウ種子抽出物(GSE)のDPPHラジカル捕捉活性の熱およびpHに対する安定性について,アスコルビン酸(AsA)と比較検討した.また,アルカリpH領域でゲル粘凋化を行う蒟蒻にGSEを配合し,そのラジカル捕捉活性の評価を行った.(1) GSEは,AsA, (+)-カテキン同様,濃度依存的にDPPHラジカル捕捉活性を示した.GSEは1分子あたりのフェノール性水酸基の数が多いため,これらの抗酸化剤中,最もラジカル捕捉活性が強かった.(2) 酸性域から中性域のpH領域で,GSEは熱に対して非常に安定だった.特に,pH 4.0, 100℃ 5時間処理でも捕捉活性をほぼ100%保持していた.(3) アルカリ域のpH領域ではGSEも若干活性の減少が見られたが,AsAと比べればはるかに熱に対して安定だった.例えば,AsAが完全に活性を失ったpH10.0, 100℃, 30分処理では,GSEは捕捉活性を約60%保持していた.以上のことより,GSEは熱,pHに対して非常に安定なDPPHラジカル捕捉化合物であることが証明された.(4) GSE配合の蒟蒻を試作し,本蒟蒻がDPPHラジカル捕捉活性を有意に示すことを確認した.同濃度配合のAsA蒟蒻では弱い活性値しか示さず,無配合蒟蒻は活性を確認できなかった.

Effect of Proanthocyanidin-Rich Extract from Grape Seeds on Human Fecal Flora and Fecal Odor

Effect of Proanthocyanidin-Rich Extract from Grape Seeds on Human Fecal Flora and Fecal Odor

Increase of antioxidative potential of rat plasma by oral administration of proanthocyanidin-rich extract from grape seeds.

The effect of a single oral administration of proanthocyanidins, oligomeric and polymeric polyhydroxyflavan-3-ol units, on the antioxidative potential of blood plasma was studied in rats. Proanthocyanidin-rich extract from grape seeds was administered by intragastric intubation to fasted rats at 250 mg/kg of body weight. The plasma obtained from water- or proanthocyanidin-administered rats was oxidized by incubation with copper sulfate or 2, 2'-azobis(2-amidinopropane) dihydrochloride (AAPH) at 37 degrees C, and the formation of cholesteryl ester hydroperoxides (CE-OOH) was followed. The plasma obtained from proanthocyanidin-administered rats was significantly more resistant against both copper ion-induced and AAPH-induced formation of CE-OOH than that from control rats. The lag phase in the copper ion-induced oxidation of rat plasma was remarkably increased at 15 min after administration of proanthocyanidins and reached a maximum level at 30 min. When the plasma from proanthocyanidin-administered rat was hydrolyzed by sulfatase and beta-glucuronidase following analysis by high-performance liquid chromatography with electrochemical detection, metabolites of proanthocyanidins occurred in rat plasma at 15 min after administration, three peaks of which were identified as gallic acid, (+)-catechin, and (-)-epicatechin. These results suggest that the intake of proanthocyanidins, the major polyphenols in red wine, increases the resistance of blood plasma against oxidative stress and may contribute to physiological functions of plant food including wine through their in vivo antioxidative ability.

Proanthocyanidin-rich extract from grape seeds attenuates the development of aortic atherosclerosis in cholesterol-fed rabbits

The aim of this study was to evaluate the antiatherosclerotic effect of proanthocyanidin-rich extracts from grape seeds in cholesterol-fed rabbits. Proanthocyanidin-rich extracts (0.1% and 1% in diets [w/w]) did not appreciably affect the changes in serum lipid profile of cholesterol-fed rabbits. The level of cholesteryl ester hydroperoxides (ChE-OOH) induced by 2,2′-azobis(2-amidinopropane-dihydrochloride (AAPH) were lower in the plasma of rabbits fed proanthocyanidin-rich extract plus cholesterol than in the plasma of rabbits fed cholesterol alone, but not in the low-density lipoprotein (LDL). Aortic malondialdehyde (MDA) content decreased in rabbits fed proanthocyanidin-rich extract. Feeding proanthocyanidin-rich extracts (0.1 and 1% in the diet) to rabbits significantly reduced severe atherosclerosis in the aorta. Immunohistochemical analysis revealed a decrease in the number of oxidized LDL-positive macrophage-derived foam cells in atherosclerotic lesions in the aorta of rabbits fed proanthocyanidin-rich extract. When proanthocyanidin-rich extract was administered orally to rats, proanthocyanidin was detected in the plasma by Porters method but not in the lipoproteins (LDL plus VLDL). In an in vitro experiment using human plasma, proanthocyanidin-rich extract added to the plasma inhibited the oxidation of cholesteryl linoleate in LDL, but not in the LDL isolated after the plasma and the extract were incubated in advance. These results suggested that proanthocyanidins, the major polyphenols in red wine, might trap reactive oxygen species in aqueous series such as plasma and interstitial fluid of the arterial wall, thereby inhibiting oxidation of LDL and showing an antiatherosclerotic activity.