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This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited., [Purpose] The grape and wine polyphenol resveratrol exerts cardiovascular benefits but evidence from randomized human clinical trials is very limited. We investigated dose-depending effects of a resveratrol-containing grape supplement on stable patients with coronary artery disease (CAD) treated according to currently accepted guidelines for secondary prevention of cardiovascular disease., [Methods] In a triple-blind, randomized, placebo-controlled, one-year follow-up, 3-arm pilot clinical trial, 75 stable-CAD patients received 350 mg/day of placebo, resveratrol-containing grape extract (grape phenolics plus 8 mg resveratrol) or conventional grape extract lacking resveratrol during 6 months, and a double dose for the following 6 months. Changes in circulating inflammatory and fibrinolytic biomarkers were analyzed. Moreover, the transcriptional profiling of inflammatory genes in peripheral blood mononuclear cells (PBMCs) was explored using microarrays and functional gene expression analysis., [Results] After 1 year, in contrast to the placebo and conventional grape extract groups, the resveratrol-containing grape extract group showed an increase of the anti-inflammatory serum adiponectin (9.6 %, p = 0.01) and a decrease of the thrombogenic plasminogen activator inhibitor type 1 (PAI-1) (−18.6 %, p = 0.05). In addition, 6 key inflammation-related transcription factors were predicted to be significantly activated or inhibited, with 27 extracellular-space acting genes involved in inflammation, cell migration and T-cell interaction signals presenting downregulation (p, [Conclusions] Chronic daily consumption of a resveratrol-containing grape nutraceutical could exert cardiovascular benefits in stable-CAD patients treated according to current evidence-based standards, by increasing serum adiponectin, preventing PAI-1 increase and inhibiting atherothrombotic signals in PBMCs., This study was supported by public funds: Projects CICYT-BFU2007-60576 and Consolider-Ingenio 2010 (CSD2007-00063, Fun-C-Food) from the Spanish Ministry of Science and Innovation (MICINN) and GERM-06-04486 (Fundación Séneca, Murcia, Spain). Dr. Tomé-Carneiro received a FPI grant from MICINN and Dr. Larrosa received a JAE-DOC contract from the Consejo Superior de Investigaciones Científicas (CSIC, Spain).

10 pages, 2 tables, 2 figures.-- Printed version published July 2004., There has been increasing interest in the research of flavonoids from dietary sources, due to growing evidence of the versatile health benefits of flavonoids through epidemiological studies. As occurrence of flavonoids is directly associated with human daily dietary intake of antioxidants, it is important to evaluate flavonoid sources in food. Fruits and vegetables are the main dietary sources of flavonoids for humans, along with tea and wine. However, there is still difficulty in accurately measuring the daily intake of flavonoids because of the complexity of existence of flavonoids from various food sources, the diversity of dietary culture, and the occurrence of a large amount of flavonoids itself in nature. Nevertheless, research on the health aspects of flavonoids for humans is expanding rapidly. Many flavonoids are shown to have antioxidative activity, free-radical scavenging capacity, coronary heart disease prevention, and anticancer activity, while some flavonoids exhibit potential for anti–human immunodeficiency virus functions. As such research progresses, further achievements will undoubtedly lead to a new era of flavonoids in either foods or pharmaceutical supplements. Accordingly, an appropriate model for a precise assessment of intake of flavonoids needs to be developed. Most recent research has focused on the health aspects of flavonoids from food sources for humans. This paper reviews the current advances in flavonoids in food, with emphasis on health aspects on the basis of the published literature, which may provide some guidance for researchers in further investigations and for industries in developing practical health agents., The authors thank the Rural Industries Research and Development Corporation (RIRDC, Australia) for financial support for this project and Department of Education, Science and Training (DEST, Australia) for providing an IPRS fund support.

9 pages, 4 figures, 5 tables., Phenolic profiles of nine red fruit commercial juice concentrates were characterised by means of high -performance liquid chromatography–diode array detection–mass spectrometry–mass spectrometry. Flavonoids such as anthocyanins, flavonols, hydroxycinnamic acid derivatives, stilbenoids, flavan 3-ols, ellagic acid derivatives, and other phenolic acids, were both identified and quantified in chokeberry, elderberry, blackcurrant and redcurrant, strawberry, red grape, cherry, plum, and raspberry commercial juice concentrates. Once the characterisation was carried out, the antioxidant capacity of each concentrate was assessed in vitro by means of two different methods: the 2,2-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (Trolox equivalent antioxidant capacity) method and the 2,2-diphenyl-1-picrylhydrazyl radical method. Elderberry, chokeberry and blackcurrant concentrates were the richest in total phenolics and they had the strongest antioxidant capacity; therefore, these three juices may have huge interest as ingredients in the design of functional juices.

16 pages, 3 tables, 7 figures.-- Online version published Jan 2004., [Background]: The antiatherogenic activity of pomegranate juice has been attributed to its antioxidant polyphenols. The most potent in vitro antioxidant polyphenol from this juice is the ellagitannin punicalagin. However, the bioavailability of ellagitannins, including punicalagin, has not been previously described in humans., [Aim of the study]: The present work aims to evaluate, in healthy humans, the bioavailability and metabolism of pomegranate juice ellagitannins, to assess their effect on several blood parameters (including cardiovascular risk disease markers) and to compare the antioxidant activity of punicalagin with that of the in vivo generated metabolites., [Design]: Six healthy subjects (four men and two women) consumed 1 L of pomegranate juice daily (5.58 g/L polyphenols, including 4.37 g/L punicalagin isomers) for 5 days. The polyphenols and the in vivo generated metabolites were measured by HPLC–DAD–MS–MS. Fourteen haematological and twenty serobiochemical parameters including LDL, HDL and VLDL as well as cholesterol and triglycerides in each lipoprotein were evaluated. In vitro antioxidant activity of plasma (ABTS and FRAP assays) and urine (ABTS and DPPH) were determined., [Results]: Neither punicalagin nor ellagic acid present in the juice were detected in both plasma and urine. Three microbial ellagitannin-derived metabolites were detected: 3,8–dihydroxy–6H–dibenzo[b,d] pyran–6–one glucuronide, an unidentified aglycone (tentatively, trihydroxy–6H–dibenzo[b,d]pyran–6–one) and hydroxy–6–Hdibenzo[ b,d]pyran–6–one glucuronide. These metabolites could reach up to 18.6 µM in plasma, although a large inter–individual variability was observed. In urine, the same metabolites and their corresponding aglycones became evident after 1 day of juice consumption. Total urine excretion of metabolites ranged from 0.7 to 52.7% regarding the ingested punicalagin. No relevant effect was observed on any blood parameter. The metabolites did not show significant antioxidant activity compared to punicalagin from pomegranate juice., [Conclusions]: The potential systemic biological effects of pomegranate juice ingestion should be attributed to the colonic microflora metabolites rather than to the polyphenols present in the juice., This research was supported by Spanish CICYT, AGL2000–2014 and by the ‘Fundación Séneca’, Project PB/18/FS/02. B. C. has a fellowship from the Spanish ‘Consejo Superior de Investigaciones Científicas’ (CSIC) and ESF (I3P Programme).

6 pages, 2 tables.-- Printed version published 2005., Ready-to-eat foods such as soups are in great demand by consumers, owing to the changes in lifestyle over the last half-century. In this context, the addition of new health-promoting active ingredients such as polyphenols could represent an important way to increase the intake of these compounds. Three different by-products from artichoke, lettuce and cauliflower handling and commercialisation have been use to obtain enriched polyphenol extract using a water extraction protocol. The artichoke by-products extract was composed of caffeic acid derivatives while the lettuce and the cauliflower by-products extract were composed of both caffeic acid derivatives and flavonols. The amounts of these compounds were evaluated with HPLC-DAD; it transpired that the artichoke by-products extract had the highest levels of polyphenols (100 mg of polyphenols/g of dry extract), followed by lettuce by-products extract (46 mg of polyphenols/g of dry extract) and cauliflower by-products extract (34 mg of polyphenols/g of dry extract). A sensory panel with four trained judges evaluated the addition of different amounts of extracts. Both artichoke and lettuce by-products extract could be added to the soup to a maximum amount of 10 mg of extract/mL of soup and cauliflower with 5 mg of extract/mL of soup, while still improving the grade of acceptability of the soup with respect to the original soup. In addition, antioxidant capacity was evaluated as free radical scavenging activity (ABTS·+ assay) and the ability to reduce the 2,4,6-tripyridyl-s-triazine (TPTZ)-Fe(III) complex to TPTZ-Fe(II) (FRAP assay). The antioxidative capacity increased with addition of the extracts between 3.5 times and 13 times (ABTS·+ assay) as well as between 23 times and 85 times (FRAP assay). The results obtained indicate that these by-products could provide the extracts with antioxidant phenolics that could be used to functionalise foods. Obviously, before incorporating these by-product extracts as dietary complements, it is necessary to carry out further studies about their toxicity (i.e. possible residual presence of pesticides), in vivo activity, and bioavailability.

11 pages, 10 figures, 1 table., [Background and Aims]: Punicalagin is an antioxidant ellagitannin of pomegranate juice. This compound is responsible for the high antioxidant activity of this juice. Nothing is known about the bioavailability and metabolism of punicalagin or other food ellagitannins. The present work aims to evaluate the bioavailability and metabolism of punicalagin in the rat as an animal model., [Design]: Two groups of rats were studied. One fed with standard rat diet (n = 5) and another with the same diet plus 6 % punicalagin (n = 5). Samples of urine and faeces were taken during 37 days and plasma every week. The different metabolites were analysed by HPLC-MS-MS., [Results]: The daily intake of punicalagin ranged from 0.6 to 1.2 g. Values around 3–6 % the ingested punicalagin were excreted as identified metabolites in faeces and urine. In faeces, punicalagin is transformed to hydrolysis products and partly metabolites by the rat microflora to 6H-dibenzo[b,d]pyran-6-one derivatives. In plasma, punicalagin was detected at concentrations around 30 μg/mL, and glucuronides of methyl ether derivatives of ellagic acid were also detected. 6H-Dibenzo[b,d]pyran-6-one derivatives were also detected especially during the last few weeks of the experiment. In urine, the main metabolites observed were the 6H-dibenzo[b,d]pyran-6-one derivatives, as aglycones or glucuronides., [Conclusion]: As only 3–6 % of the ingested punicalagin was detected as such or as metabolites in urine and faeces, the majority of this ellagitannin has to be converted to undetectable metabolites (i. e. CO2) or accumulated in non-analysed tissues, however with only traces of punicalagin metabolites being detected in liver or kidney. This is the first report on the absorption of an ellagitannin and its presence in plasma. In addition, the transformation of ellagic acid derivatives to 6H-dibenzo[b,d]pyran-6-one derivatives in the rat is also confirmed., This work has been supported by Spanish CICYT, AGL2000–2014). B. C. has a fellowship from the Spanish “Consejo Superior de Investigaciones Científicas” (CSIC) and ESF (I3P Programme).

5 pages, 3 tables, 2 figures., The flavonol content of commercial capers (pickled flower buds of Capparis spinosa L., C. sicula Veill. in Duham. and C. orientalis Veill. in Duham.) produced in different Mediterranean countries (Spain, Italy, Greece, Turkey and Morocco) has been analysed. The content of quercetin 3-rutinoside, kaempferol 3-rutinoside; and kaempferol 3-rhamnosyl-rutinoside as well as the aglycones (quercetin and kaempferol) were evaluated by HPLC coupled with a diode-array detector. The free aglycones were not detected in the original flower buds, indicating that they were produced during the brining process. In addition, brining extracted most of the kaempferol 3-rhamnosyl rutinoside present in the original buds, this being a minor constituent in pickled capers. The average content of flavonoid glycosides in commercial capers was 5.18 mg/g fresh weight. When this value is converted to the corresponding aglycones (quercetin and kaempferol), capers provide an average of 3.86 mg/g fresh weight. A serving of capers (10 g) will provide 65 mg of flavonoid glycosides or the equivalent 40 mg of quercetin as aglycone., This work has been financially supported by the Spanish CICYT (AGF-96–1040).