Cardioprotective actions of grape polyphenols

The aim of this review is to discuss the accumulating evidence that suggests that grape extracts and purified grape polyphenols possess a diverse array of biological actions and may be beneficial in the prevention of some inflammatory-mediated diseases including cardiovascular disease. The active components from grape extracts, which include the grape seed, grape skin, and grape juice, that have been identified thus far include polyphenols such as resveratrol, phenolic acids, anthocyanins, and flavonoids. All possess potent antioxidant properties and have been shown to decrease low-density lipoprotein–cholesterol oxidation and platelet aggregation. These compounds also possess a range of additional cardioprotective and vasoprotective properties including antiatherosclerotic, antiarrhythmic, and vasorelaxation actions. Although not exclusive, antioxidant properties of grape polyphenols are likely to be central to their mechanism(s) of action, which also include cellular signaling mechanisms and interactions at the genomic level. This review discusses some of the evidence favoring the consumption of grape extracts rich in polyphenols in the prevention of cardiovascular disease. Consumption of grape and grape extracts and/or grape products such as red wine may be beneficial in preventing the development of chronic degenerative diseases such as cardiovascular disease     

Resveratrol and its glycon piceid are stable polyphenols

Plant extracts containing phytopolyphenols, including resveratrol, are extensively used as nutraceutical supplements. Recent reports allege their lack of stability at ambient conditions. We have studied the stability of resveratrol and its glycon piceid in a mixture with a whole grape extract for 2 years (long-term stability) under Good Manufacturing Practice pharmaceutical protocols (at 60% humidity and 25 degrees C). The neat compounds were followed for 4 years under conditions of "accelerated stability," at 75% humidity and 40 degrees C, all in the presence of ambient air. Chromatographic analysis did not detect any instability, thus disproving the claims to the opposite. No storage precautions are necessary for these nutritional supplements.     

Anticarcinogenic Effects of Dietary Phytoestrogens and Their Chemopreventive Mechanisms

Phytoestrogens are phenolic compounds derived from plants and exert an estrogenic as well as an antiestrogenic effect and also various biological efficacies. Chemopreventive properties of phytoestrogens has emerged from epidemiological observations indicating that the incidence of some cancers including breast and prostate cancers is much lower in Asian people, who consume significantly higher amounts of phytoestrogens than Western people. There are 4 main classes of phytoestrogens: isoflavones, stilbenes, coumestans, and lignans. Currently, resveratrol is recognized as another major phytoestrogen present in grape and red wine and has been studied in many biological studies. Phytoestrogens have biologically diverse profitabilities and advantages such as low cytotoxicity to patients, lack of side effects in clinical trials, and pronounced benefits in a combined therapy. In this review, we highlighted the effects of genistein, daidzein, and resveratrol in relation with their anticarcinogenic activity. A lot of in vitro and in vivo results on their chemopreventive properties were presented along with the underlying mechanisms. Besides well-known mechanisms such as antioxidant property and apoptosis, newly elucidated anticarcinogenic modes of action including epigenetic modifications and topoisomerase inhibition have been provided to examine the possibility of phytoestrogens as promising reagents for cancer chemoprevention and/or treatment and to suggest the importance of plant-based diet of phytoestrogens.     

Neuroprotective Effect of Eco-Sustainably Extracted Grape Polyphenols in Neonatal Hypoxia-Ischemia

Polyphenols are natural compounds with promising prophylactic and therapeutic applications. However, their methods of extraction, using organic solvents, may prove to be unsuitable for daily consumption or for certain medical indications. Here, we describe the neuroprotective effects of grape polyphenols extracted in an eco-sustainable manner in a rat model of neonatal hypoxia-ischemia (NHI). Polyphenols (resveratrol, pterostilben and viniferin) were obtained using a subcritical water extraction technology to avoid organic solvents and heavy metals associated with chemical synthesis processes. A resveratrol or a polyphenol cocktail were administered to pregnant females at a nutritional dose and different time windows, prior to induction of NHI in pups. Reduced brain edema and lesion volumes were observed in rat pups whose mothers were supplemented with polyphenols. Moreover, the preservation of motor and cognitive functions (including learning and memory) was evidenced in the same animals. Our results pave the way to the use of polyphenols to prevent brain lesions and their associated deficits that follow NHI, which is a major cause of neonatal death and disabilities.     

Terroir and variety: Two key factors for obtaining stilbene-enriched grapes

Grapes and wine are among the main sources of bioactive stilbenes in the diet. The stilbene composition of grapes depends on both variety and terroir. The effect of terroir on grape stilbenes has not been widely studied. In this research the study of the stilbene content (resveratrol, piceatannol and viniferins) in four different red grape varieties (Syrah, Merlot, Cabernet sauvignon and Pinot noir) and from four different Andalusian terroirs (Jerez, Cabra, Cadiar and Ronda) was carried out during the 2009 vintage. In addition, stilbene induction capacity was studied in each terroir and variety after ultraviolet-C (UVC) postharvest treatment. Data were analysed by multivariate statistical methods. Principal component analysis applied to the oenological parameters and stilbene data classified varieties into two terroir groups satisfactorily: Jerez and Cabra on the one hand, and Ronda and Cadiar on the other hand. Terroir effect is stronger than variety on stilbene induction capacity after UVC treatment. Syrah from Cabra stood out due to both the high basal (13.07 mg/kg fw) and induced (33.14 mg/kg fw) stilbene concentration attained. Therefore, it can be affirmed that Cabra and Syrah are the most suitable terroir and variety, respectively, for obtaining a stilbene-enriched wine.     

Total phenolic contents and free-radical scavenging activities of grape (Vitis vinifera L.) and grape products

Grape is one of the world's largest fruit crops, with an approximate annual production of 58 million metric tons, and it is well known that the grape skins, seeds and stems, waste products generated during wine and grape juice processing, are rich sources of polyphenols. It contains flavonoids, phenolic acids and stilbenes. In this study, we tried to determine antioxidant properties and phenolic contents of grape and grape products (fresh fruit, seed, dried fruit, molasses, pestil, vinegar) of ethanol and water extracts. Antioxidant properties of extracts were investigated by DPPH^√, ABTS^√+, superoxide, H₂O₂ scavenging, reducing power, metal chelating activity and determination of total phenolic contents. The seed extracts revealed highest ABTS^√+, DPPH^√, H₂O₂ scavenging and reducing power activities. Furthermore, these extracts showed higher total phenolic contents than other grape product extracts.     

葡萄汁对人前列腺癌PC-3细胞增殖和凋亡的影响

目的:探讨葡萄汁对人前列腺癌PC-3细胞生长抑制的作用及其机制。方法:白藜芦醇及不同浓度葡萄汁作用于人前列腺癌PC-3细胞48h;采用生长曲线及噻唑蓝(MTT)法检测葡萄汁、白藜芦醇对人前列腺癌PC-3细胞的生长抑制作用,通过原位(缺口)末端标记法(TUNEL)观察凋亡细胞的形态结构变化,流式细胞仪检测细胞凋亡峰。结果:葡萄汁、白藜芦醇能显著抑制人前列腺癌PC-3细胞生长;TUNEL方法检测呈阳性;流式细胞仪分析图上出现典型的凋亡细胞峰。以上各指标中,葡萄汁随着浓度增大作用加强;低剂量组的作用比白藜芦醇组差,中、高剂量组的白藜芦醇浓度低,但作用比白藜芦醇组强。结论:葡萄汁对抗人前列腺癌PC-3细胞的作用,除白藜芦醇外,可能还存在其他抗癌成分的作用。葡萄汁、白藜芦醇对PC-3细胞生长抑制作用的机制可能与其诱导人前列腺癌PC-3细胞凋亡有关。     

A berry thought-provoking idea: the potential role of plant polyphenols in the treatment of age-related cognitive disorders

Today, tens of millions of elderly individuals worldwide suffer from dementia. While the pathogenesis of dementia is complex and incompletely understood, it may be, at least to a certain extent, the consequence of systemic vascular pathology. The metabolic syndrome and its individual components induce a proinflammatory state that damages blood vessels. This condition of chronic inflammation may damage the vasculature of the brain or be directly neurotoxic. Associations have been established between the metabolic syndrome, its constituents and dementia. A relationship has also been observed between certain dietary factors, such as constituents of the 'Mediterranean diet', and the metabolic syndrome; similar associations have been noted between these dietary factors and dementia. Fruit juices and extracts are under investigation as treatments for cognitive impairment. Blueberry, strawberry, blackberry, grape and plum juices or extracts have been successfully tested in cognitively impaired rodents. Published trials of the benefits of grape and blueberry juice in the treatment of small numbers of cognitively impaired persons have recently appeared. The benefits of fruit products are thought to be a result of its polyphenol content. A grape polyphenol found in grapes, resveratrol, now being studied in humans, and one in grapes and blueberries, pterostilbene, have been found to improve cognition in rodents. In the design of future human trials, one ought to consider the poor bioavailability of these products, the possible need to initiate the experimental therapy long before the onset of symptoms, and currently limited knowledge about the appropriate form (e.g. juice, powder or individual polyphenol) of treatment.     

高效液相色谱法测定葡萄皮和葡萄籽中白藜芦醇的含量

测定不同品种葡萄皮和葡萄籽及酿酒后的葡萄皮渣中白藜芦醇的含量。应用乙腈 -水 (2 6∶74 )为流动相 ,检测波长 (λ)为 30 3nm ,柱温为 35℃ ,色谱柱 :SUPELCOSILTMLC 18(2 5 0mm× 4 6mm ,5 μm)。结果显示 ,葡萄皮中的白藜芦醇含量高于葡萄籽 ;不同品种葡萄皮中白藜芦醇含量差异较大 ,琐琐葡萄最低为0 985 0 μg g ,红克里米斯克葡萄最高为 15 4 195 μg g;同一产地同一品种葡萄皮中白藜芦醇含量依次为酿酒后的葡萄皮 >新鲜葡萄皮 >陈旧葡萄皮 ,且差异有统计学意义     

葡萄酒中游离白藜芦醇的气相色谱质谱测定法

目的 :　建立葡萄酒中游离白藜芦醇的气相色谱 -质谱测定方法。方法 :　样品经过除乙醇 ,用乙酸乙酯提取出游离白藜芦醇 ,然后用 BSTFA+1 % (φ) TMCS衍生 ,氮气吹干后用甲苯溶解 ,采用 GCMS对顺式、反式白藜芦醇同时进行定性、定量分析。结果 :　葡萄酒中添加0 .2 5～ 1 .2 5 mg/L浓度水平的白藜芦醇 ,方法回收率在 85 .6%～ 1 1 0 .5 % ,相对标准偏差为 8.2 %～ 1 1 .5 % ,在 0 .5 0～ 1 0 .0 0 mg/L浓度范围内测定线性相关系数 r为 0 .995 ,葡萄酒中游离白藜芦醇的最低检测限为 0 .0 0 5 mg/L;对 1 5种国产葡萄酒进行白藜芦醇含量检测 ,顺式白藜芦醇含量范围为 0 .0 2～ 0 .5 6mg/L,反式白藜芦醇含量范围为 0 .1 5～ 1 .2 8mg/L,总的游离白藜芦醇含量范围为 0 .2 6～ 1 .48mg/L。结论 :　本研究建立的气相色谱质谱法能准确地对葡萄酒中游离白藜芦醇进行定性、定量分析     

Modifications in the Intestinal Functionality,Morphology and Microbiome Following Intra-Amniotic Administration (Gallus gallus) of Grape (Vitis vinifera) Stilbenes (Resveratrol and Pterostilbene)

This efficacy trial evaluated the effects of two polyphenolic stilbenes, resveratrol and pterostilbene, mostly found in grapes, on the brush border membrane functionality, morphology and gut microbiome. This study applied the validated Gallus gallus intra-amniotic approach to investigate the effects of stilbene administration versus the controls. Three treatment groups (5% resveratrol; 5% pterostilbene; and synergistic: 4.75% resveratrol and 0.25% pterostilbene) and three controls (18 MΩ H₂O; no injection; 5% inulin) were employed. We observed beneficial morphological changes, specifically an increase in the villus length, diameter, depth of crypts and goblet cell diameter in the pterostilbene and synergistic groups, with concomitant increases in the serum iron and zinc concentrations. Further, the alterations in gene expression of the mineral metabolism proteins and pro-inflammatory cytokines indicate a potential improvement in gut health and mineral bioavailability. The cecal microbiota was analyzed using 16S rRNA sequencing. A lower α-diversity was observed in the synergistic group compared with the other treatment groups. However, beneficial compositional and functional alterations in the gut microbiome were detected. Several key microbial metabolic pathways were differentially enriched in the pterostilbene treatment group. These observations demonstrate a significant bacterial–host interaction that contributed to enhancements in intestinal functionality, morphology and physiological status. Our data demonstrate a novel understanding of the nutritional benefits of dietary stilbenes and their effects on intestinal functionality, morphology and gut microbiota in vivo.     

Concentrations of resveratrol and derivatives in foods and estimation of dietary intake in a Spanish population: European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort

Resveratrol has been shown to have beneficial effects on diseases related to oxidant and/or inflammatory processes and extends the lifespan of simple organisms including rodents. The objective of the present study was to estimate the dietary intake of resveratrol and piceid (R&P) present in foods, and to identify the principal dietary sources of these compounds in the Spanish adult population. For this purpose, a food composition database (FCDB) of R&P in Spanish foods was compiled. The study included 40,685 subjects aged 35-64 years from northern and southern regions of Spain who were included in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. Usual food intake was assessed by personal interviews using a computerised version of a validated diet history method. An FCDB with 160 items was compiled. The estimated median and mean of R&P intake were 100 and 933 microg/d respectively. Approximately, 32% of the population did not consume R&P. The most abundant of the four stilbenes studied was trans-piceid (53.6%), followed by trans-resveratrol (20.9%), cis-piceid (19.3%) and cis-resveratrol (6.2%). The most important source of R&P was wines (98.4%) and grape and grape juices (1.6%), whereas peanuts, pistachios and berries contributed to less than 0.01%. For this reason the pattern of intake of R&P was similar to the wine pattern. This is the first time that R&P intake has been estimated in a Mediterranean country.     

Mediterranean diet and cardioprotection: the role of nitrite, polyunsaturated fatty acids, and polyphenols

The continually increasing rate of myocardial infarction (MI) in the Western world at least partly can be explained by a poor diet lacking in green vegetables, fruits, and fish and enriched in food that contains saturated fat. In contrast, a number of epidemiologic studies provide strong evidence highlighting the cardioprotective benefits of the Mediterranean diet enriched in green vegetables, fruits, fish, and grape wine. Regular consumption of these products leads to an accumulation of nitrate/nitrite/NO, polyunsaturated fatty acids (PUFA), and polyphenolic compounds, such as resveratrol, in the human body. Studies have confirmed that these constituents are bioactive exogenous mediators, which induce strong protection against MI. The aim of this review is to provide a critical, in-depth analysis of the cardioprotective pathways mediated by nitrite/NO, PUFA, and phenolic compounds of grape wines discovered in the recent years, including cross-talk between different mechanisms and compounds. Overall, these findings may facilitate the design and synthesis of novel therapeutic tools for the treatment of MI.     

Phytochemical Compounds and Antioxidant Capacity of Tucum-Do-Cerrado (Bactris setosa Mart), Brazil’s Native Fruit

This study identified major phenolic compounds of the tucum-do-cerrado (Bactris setosa) peel, as well as antioxidant activity and total phytochemical compound concentration of different extracts of the peel and pulp of this fruit. Phenolic compounds of the different extracts of tucum-do-cerrado peel were identified and quantified using a high-performance liquid chromatography system coupled to a diode array detector (DAD). Total phytochemical compound content was determined by spectrophotometric assays and the antioxidant activity by ferric reducing antioxidant power and β-carotene/linoleic assays. Total phenolic, flavanols, total anthocyanins and yellow flavonoids concentration of tucum-do-cerrado were 122-, 14-, 264- and 61-fold higher in the peel than in the pulp, respectively. The aqueous, methanolic and ethanolic extracts of the tucum-do-cerrado peel exhibited higher antioxidant activity compared to its pulp. Flavanols, anthocyanins, flavones, phenolic acids and stilbenes were the main phenolic classes identified in the tucum-do-cerrado peel extracts. Results suggest that the antioxidant capacity and the phytochemical compound content of the tucum-do-cerrado are mainly associated with the peel. Although flavonoids are the main compounds identified in tucum-do-cerrado peel, other phenolics identified in minor amounts, such as phenolic acids and stilbenes, may be responsible for the high antioxidant capacity of the fruit.     

The Role of Resveratrol in Eye Diseases—A Review of the Literature

Resveratrol (3,5,4′-trans-trihydroxystilbene) is a polyphenolic phytoalexin belonging to the stilbene family. It is commonly found in grape skins and seeds, as well as other plant-based foods. Oxidative stress and inflammation play a key role in the initiation and progression of age-related eye disorders (glaucoma, cataracts, diabetic retinopathy, and macular degeneration) that lead to a progressive loss of vision and blindness. Even though the way resveratrol affects the human body and the course of many diseases is still the subject of ongoing scientific research, it has been shown that the broad spectrum of anti-inflammatory and neuroprotective properties of resveratrol has a beneficial effect on eye tissues. In our research, we decided to analyze the current scientific literature on resveratrol, its possible mechanisms of action, and its therapeutic application in order to assess its effectiveness in eye diseases.     

Discrimination of five Greek red grape varieties according to the anthocyanin and proanthocyanidin profiles of their skins and seeds

The knowledge of grapes phenolic content is proven to be critical for the vinification process and the improvement of wine quality. This study was undertaken to determine the phenolic composition and to employ the phenolic profile as a varietal discrimination tool in five Greek red grape varieties. Ninety grape samples from two seasons (2017 and 2018) were analyzed after extraction with organic solvents. Their proanthocyanidin profile, expressed as percentages of flavan-3-ols, was determined in both skins and seeds by employing phloroglucinolysis followed by HPLC-UV and MS detection, and anthocyanin profile was identified only in the skin extracts by HPLC-UV. Significant differences were observed in proanthocyanidin and anthocyanin profiles of skin extracts between the samples of different varieties, but not in seeds. (-)-Epicatechin was the main subunit in Mandilaria, Kotsifali, Agiorgitiko and Xinomavro grapes while (-)-epigallocatechin gallate in Mavrotragano. Malvidin-3-O-glucoside was the predominant pigment in all grape samples analyzed with the exception of Kotsifali skin extracts, where peonidin-3-O-glucoside was the most abundant anthocyanin. In addition, Mavrotragano skin extracts were the richest in delphinidin and petunidin-3-O-glucosides, while Agiorgitiko and Xinomavro contained the highest amount of malvidin-3-O-glucoside. The results underline the significance of the skin phenolic composition as a tool for the discrimination of the Greek red grape varieties.     

Disparate in vitro and in vivo antileukemic effects of resveratrol,a natural polyphenolic compound found in grapes

Resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenol found in grapes and grape wine, has been reported to exhibit cardioprotective and chemopreventive activity against chemical carcinogenesis. It has also been shown to have growth inhibitory activity toward solid tumors in vivo. However, the antitumor activity of resveratrol against hematologic tumors in vivo has not been examined. In this study, the antileukemic activity of resveratrol in vitro and in vivo was examined using a mouse myeloid leukemia cell line (32Dp210). Treatment of 32Dp210 leukemia cells with resveratrol at micromolar concentrations (25-50 micromol/L) significantly and irreversibly inhibited their clonal growth in vitro. The clonal growth inhibition by resveratrol was associated with extensive cell death and an increase in hypodiploid (sub-G1) cells. Resveratol caused internucleosomal DNA fragmentation, suggesting apoptosis as the mode of cell death in 32Dp210 cells. DNA fragmentation was associated with activation of caspase-3, because cleavage of procaspase-3 was detected in resveratrol-treated cells. Although 32Dp210 cells treated with resveratrol in vitro did not produce leukemia in vivo, only a weak antileukemic effect of resveratrol was observed when administered orally. At doses of 8 mg or 40 mg/kg body daily, five times/wk, resveratrol did not affect the survival of mice injected with leukemia cells. Weak potential antileukemic activity of resveratrol was suggested only at a dose of 80 mg/kg body (2 survivors of 14 mice treated). Thus, despite strong antiproliferative and proapoptotic activities of resveratrol against 32Dp210 cells in vitro, a potential antileukemia effect in vivo, if present, occurs only in a small fraction of mice.     

The polyphenol-rich extracts from black chokeberry and grape seeds impair changes in the platelet adhesion and aggregation induced by a model of hyperhomocysteinemia

Objective

The mechanism action of the polyphenol-rich extracts from berries of Aronia melanocarpa (black chokeberry) and from grape seeds in the defence against homocysteine (Hcy) and its derivatives action in blood platelets is still unknown. In this study, the influence of the aronia extract and grape seeds extract (GSE) on the platelet adhesion to collagen and fibrinogen and the platelet aggregation during a model of hyperhomocysteinemia was investigated. The aim of our study in vitro was also to investigate superoxide anion radicals (O ₂ ^?? ) production after incubation of platelets with Hcy, HTL and the aronia extract and GSE during a model of hyperhomocysteinemia (induced by reduced form of homocysteine at final dose of 100 μM) and the most reactive form of Hcy—its cyclic thioester, homocysteine thiolactone (HTL, 1 μM). Moreover, the additional aim of our study was also to establish and compare the influence of the aronia extract, GSE and resveratrol (3,4′,5-trihydroxystilben), a phenolic compound, which has been supposed to be beneficial for the prevention of cardiovascular events, on selected steps of platelet activation.

Methods

The effects of tested extracts on adhesion of blood platelets to collagen and fibrinogen were determined according to Tuszynski and Murphy. The platelet aggregation was determined by turbidimetry method using a Chrono-log Lumi-aggregometer.

Results

We have observed that HTL, like its precursor—Hcy stimulated the generation of O ₂ ^?? (measured by the superoxide dismutase—inhibitable reduction of cytochrome c) in platelets and caused an augmentation of the platelet adhesion and aggregation induced by the strong physiological agonist—thrombin. Our present results in vitro also demonstrated that the aronia extract and grape seeds extract reduced the toxicity action of Hcy and HTL on blood platelet adhesion to collagen and fibrinogen, the platelet aggregation and superoxide anion radicals production in platelets, suggesting its potential protective effects on hemostasis during hyperhomocysteinemia.

Conclusion

In the comparative studies, the aronia extract was found to be more effective antiplatelet factors, than GSE or resveratrol during a model of hyperhomocysteinemia. It gives hopes for development of diet supplements, which may be important during hyperhomocysteinemia.     

Intake of purple grape juice as a hepatoprotective agent in Wistar rats

Grape juice is a source of polyphenols, as catechin, anthocyanidins, resveratrol, and others. Some health benefits have been attributed to these compounds (e.g., antioxidant and antitumorigenic properties). In this study, we investigated the possible antioxidant activity of two different grape juices: organic purple grape juice and conventional purple grape juice. The antioxidant activity of both grape juices was evaluated by an animal model of three groups: control and organic and conventional juices. After 30 days, all animals were sacrificed, and blood and liver were collected to evaluate lipid peroxidation level (thiobarbituric acid-reactive substances [TBARS] assay), protein oxidative level (carbonyl assay), and catalase (CAT) and superoxide dismutase (SOD) activities. The group treated with organic grape juice showed the highest SOD and CAT activities in both plasma and liver when compared with the conventional and control groups (P < .05). In plasma, we observed a positive correlation among SOD and CAT activities, resveratrol, and all anthocyanin contents, suggesting that these polyphenols may be, at least in part, responsible for this increased antioxidant defense. The grape juices were capable of reducing carbonyl and lipid peroxidation levels in plasma and liver. However, in plasma, the organic group showed lower carbonyl and TBARS levels when compared to the conventional grape juice group (P < .05). Our findings suggest that the intake of purple grape juice, especially of organic juice, induces a better antioxidant capacity when compared to conventional juice and that this may be an important issue for further investigations in the area of biochemical functional foods.