Research Group on Quality

Safety, Spain

Research Group on Quality

Safety, Spain
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Gimenez-Bastida J.A.,Research Group on Quality | Gimenez-Bastida J.A.,CSIC - Center of Edafology and Applied Biology of the Segura | Gonzalez-Sarrias A.,Research Group on Quality | Gonzalez-Sarrias A.,CSIC - Center of Edafology and Applied Biology of the Segura | And 8 more authors.
Molecular Nutrition and Food Research | Year: 2012

Scope: Numerous in vitro and in vivo studies indicate that ellagitannins exhibit anti-inflammatory, anti-atherosclerotic and anti-angiogenic activity which support their potential preventive effect against cardiovascular diseases. Ellagitannins exhibit low bioavailability and are transformed in the gut to ellagic acid and its microbiota metabolites urolithin A (Uro-A) and urolithin B (Uro-B). Urolithins are found in plasma mostly as glucuronides at low μM concentrations. We investigated whether urolithin glucuronides and their aglycones exhibit vascular protective effects. Methods and results: Human aortic endothelial cells were exposed to tumor necrosis factor alpha and to Uro-A glucuronide, Uro-B glucuronide or their corresponding aglycones at low μM concentrations to determine their effects on monocytes adhesion and endothelial cell migration. The levels of related adhesion cytokines and growth molecular markers were also measured. Uro-A glucuronide (∼5-15 μM) inhibited monocyte adhesion and endothelial cell migration in a significant manner. These effects were associated with a moderate but significant down-regulation of the levels of chemokine (C-C motif) ligand 2 (CCL2) and plasminogen activator inhibitor-1 (PAI-1). Uro-A inhibited endothelial cell migration and was able to decrease the expression of CCL2 and interleukin-8 (IL-8). Conclusion: Our results suggest that these metabolites might be involved, at least in part, in the beneficial effects against cardiovascular diseases attributed to the consumption of ellagitannin-containing foods. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Truchado P.,Research Group on Quality | Larrosa M.,Research Group on Quality | Garcia-Conesa M.T.,Research Group on Quality | Cerda B.,San Antonio de Murcia Catholic University | And 3 more authors.
Journal of Agricultural and Food Chemistry | Year: 2012

The study of fruit and vegetable processing and its effects on the levels of health-promoting constituents and their bioavailability and metabolism is very relevant to understanding the role of these constituents in human health. Strawberry polyphenols, and particularly ellagitannins and ellagic acid, have been associated with the health benefits of this berry for humans. These compounds are transformed into urolithins by the gut microbiota, and these metabolites exert several biological activities that could be responsible for the health effects of strawberries. Processing potentially increases the extraction of ellagitannins from the strawberry achenes and the release of ellagic acid from ellagitannins. It is of interest to evaluate the effect of processing on strawberry ellagitannin microbial metabolism compared with fresh strawberries. This study shows that no significant differences in the production and excretion of urolithins were found between the intake of fresh strawberries and that of a thermally processed strawberry puree containing the same amount of strawberries. Processing increases the amount of free ellagic acid 2.5-fold, but this had no effect on the transformation in urolithins by the gut microbiota or in the excretion of urolithin metabolites (urolithin glucuronides) in urine, showing that the release of ellagic acid from ellagitannins is not a relevant factor affecting the microbial metabolism. All of the volunteers produced urolithin A, but only 3 of 20 volunteers produced and excreted urolithin B. It is confirmed that some volunteers were efficient producers of urolithins, whereas other produced much lower amounts. These results show that processing does not modify the potential health effects of strawberry polyphenols. © 2011 American Chemical Society.


Selma M.V.,Research Group on Quality | Beltran D.,Research Group on Quality | Garcia-Villalba R.,Research Group on Quality | Espin J.C.,Research Group on Quality | Tomas-Barberan F.A.,Research Group on Quality
Food and Function | Year: 2014

Ellagitannin and ellagic acid metabolism to urolithins in the gut shows a large human interindividual variability and this has been associated with differences in the colon microbiota. In the present study we describe the isolation of one urolithin-producing strain from the human faeces of a healthy volunteer and the ellagic acid transformation to different urolithin metabolites by two species of intestinal bacteria. The isolate belongs to a new species described as Gordonibacter urolithinfaciens, sp. nov. The type strain of the Gordonibacter genus, Gordonibacter pamelaeae DSM 19378T, was also demonstrated to produce urolithins. Both human intestinal bacteria grew similarly in the presence and absence of ellagic acid at 30 μM concentration. Ellagic acid catabolism and urolithin formation occurred during the stationary phase of the growth of the bacteria under anaerobic conditions. The HPLC-MS analyses showed the sequential production of pentahydroxy-urolithin (urolithin M-5), tetrahydroxy-urolithin (urolithin M-6) and trihydroxy-urolithin (urolithin C), while dihydroxy-urolithins (urolithin A and isourolithin A), and monohydroxy-urolithin (urolithin B) were not produced in pure cultures. Consequently, either other bacteria from the gut or the physiological conditions found in vivo are necessary for completing metabolism until the final urolithins (dihydroxy and monohydroxy urolithins) are produced. This is the first time that the urolithin production capacity of pure strains has been demonstrated. The identification of the urolithin-producing bacteria is a relevant outcome as urolithin implication in health (cardiovascular protection, anti-inflammatory and anticarcinogenic properties) has been supported by different bioassays and urolithins can be used in the development of functional foods and nutraceuticals. This study represents an initial work that opens interesting possibilities of describing enzymatic activities involved in urolithin production that can help in understanding both the human interindividual differences in polyphenol metabolism, the microbial pathways involved, and the role of polyphenols in human health. The presence of urolithin producing bacteria can indirectly affect the health benefits of ellagitannin consumption. © the Partner Organisations 2014.


Gonzalez-Sarrias A.,Research Group on Quality | Tome-Carneiro J.,Research Group on Quality | Bellesia A.,University of Modena and Reggio Emilia | Tomas-Barberan F.A.,Research Group on Quality | Espin J.C.,Research Group on Quality
Food and Function | Year: 2015

Chemotherapy increases the overall survival in colorectal cancer (CRC) patients. 5-Fluorouracil (5-FU) remains as a drug of first choice in CRC therapy over the last four decades. However, only 10-15% of patients with advanced CRC respond positively to 5-FU monotherapy. Therefore, new strategies to enhance the 5-FU effectiveness, overcome the tumor cell resistance and decrease the unspecific toxicity are critically needed. Urolithin A (Uro-A) is the main metabolite produced by the human gut microbiota from the dietary polyphenol ellagic acid. Uro-A targets the colonic mucosa of CRC patients, and preclinical studies have shown the anti-inflammatory and cancer chemopreventive activities of this metabolite. We evaluated here whether Uro-A, at concentrations achievable in the human colorectum, could sensitize colon cancer cells to 5-FU and 5′DFUR (a pro-drug intermediate of 5-FU). We found that both 5-FU and 5′DFUR arrested the cell cycle at the S phase by regulating cyclins A and B1 in the human colon cancer cells Caco-2, SW-480 and HT-29, and also triggered apoptosis through the activation of caspases 8 and 9. Co-treatments with Uro-A decreased IC50 values for both 5-FU and 5′DFUR and additionally arrested the cell cycle at the G2/M phase together with a slight increase in caspases 8 and 9 activation. Overall, we show that Uro-A potentiated the effects of both 5-FU and 5′DFUR on colon cancer cells. This suggests the need for lower 5-FU doses to achieve similar effects, which could reduce possible adverse effects. Further in vivo investigations are warranted to explore the possible role of Uro-A as a chemotherapy adjuvant. This journal is © The Royal Society of Chemistry.


Vaquero M.R.,Research Group on Quality | Yanez-Gascon M.-J.,Research Group on Quality | Villalba R.,Research Group on Quality | Larrosa M.,Research Group on Quality | And 6 more authors.
PLoS ONE | Year: 2012

Background: Rosemary (Rosmarinus officinalis L.) extracts (REs) exhibit hepatoprotective, anti-obesity and anti-inflammatory properties and are widely used in the food industry. REs are rich in carnosic acid (CA) and carnosol which may be responsible for some of the biological activities of REs. The aim of this study was to investigate whether inhibition of lipase activity in the gut may be a mechanism by which a RE enriched in CA (40%) modulates body weight and lipids levels in a rat model of metabolic disorders and obesity. Methods and Principal Findings: RE was administered for 64 days to lean (fa/+) and obese (fa/fa) female Zucker rats and body weight, food intake, feces weight and blood biochemical parameters were monitored throughout the study. Lipase activity (hydrolysis of p-nitrophenylbutyrate) was measured in the gastrointestinal tract at the end of the study and the contents of CA, carnosol and methyl carnosate were also determined. Sub-chronic administration of RE moderately reduced body weight gain in both lean and obese animals but did not affect food intake. Serum triglycerides, cholesterol and insulin levels were also markedly decreased in the lean animals supplemented with RE. Importantly, lipase activity was significantly inhibited in the stomach of the RE-supplemented animals where the highest content of intact CA and carnosol was detected. Conclusions: Our results confirm that long-term administration of RE enriched in CA moderates weight gain and improves the plasma lipids profile, primarily in the lean animals. Our data also suggest that these effects may be caused, at least in part, by a significant inhibition of gastric lipase and subsequent reduction in fat absorption. © 2012 Romo Vaquero et al.


Selma M.V.,Research Group on Quality | Martinez-Sanchez A.,Research Group on Quality | Allende A.,Research Group on Quality | Ros M.,Organic Waste Management | And 2 more authors.
Journal of Agricultural and Food Chemistry | Year: 2010

The effect of soil amendments prepared from organic wastes (sewage sludge and urban solid waste) at two concentrations (45 t ha-1 as D1 and 135 t ha-1 as D2) was evaluated on phytochemicals and microbial quality of rocket, a highly valuable vegetable. The addition of sewage sludge to the soil increased rocket yield 5.5 times compared to control and urban solid waste. Organic amendments increased the water content and the maturity stage of the leaves, which contributed to a reduction in the content of total and individual glucosinolates as well as flavonols and anthocyanins. However, higher content of vitamin C was observed after cultivation with sewage sludge at D2 compared to control leaves (204.6 and 177.4 mg 100 g-1 of fw, respectively). This study shows that sewage sludge at optimum doses can be considered a suitable amendment because of increased crop yield without detrimental effects on phytochemicals, including vitamin C content, when the leaves reached the commercial maturity stage. © 2010 American Chemical Society.


Espin J.C.,Research Group on Quality | Larrosa M.,Research Group on Quality | Garcia-Conesa M.T.,Research Group on Quality | Tomas-Barberan F.,Research Group on Quality
Evidence-based Complementary and Alternative Medicine | Year: 2013

The health benefits attributed to pomegranate have been associated with its high content in polyphenols, particularly ellagitannins. This is also the case for other ellagitannin-containing fruits and nuts including strawberry, raspberry, blackberry, walnuts, and muscadine grapes. The bioavailability of ellagitannins and ellagic acid is however very low. These molecules suffer extensive metabolism by the gut microbiota to produce urolithins that are much better absorbed. Urolithins circulate in plasma as glucuronide and sulfate conjugates at concentrations in the range of 0.2-20 M. It is therefore conceivable that the health effects of ellagitannin-containing products can be associated with these gut-produced urolithins, and thus the evaluation of the biological effects of these metabolites is essential. Recent research, mostly based on in vitro testing, has shown preliminary evidence of the anti-inflammatory, anticarcinogenic, antiglycative, antioxidant, and antimicrobial effects of urolithins, supporting their potential contribution to the health effects attributed to pomegranate and ellagitannin-rich foods. The number of in vivo studies is still limited, but they show preventive effects of urolithins on gut and systemic inflammation that encourage further research. Both in vivo and mechanistic studies are necessary to clarify the health effects of these metabolites. Attention should be paid when designing these mechanistic studies in order to use the physiologically relevant metabolites (urolithins in gut models and their conjugated derivatives in systemic models) at concentrations that can be reached in vivo. © 2013 Juan Carlos Espín et al.


Gonzalez-Sarrias A.,Research Group on Quality | Gimenez-Bastida J.A.,Research Group on Quality | Nunez-Sanchez M.A.,Research Group on Quality | Larrosa M.,Research Group on Quality | And 3 more authors.
European Journal of Nutrition | Year: 2014

Purpose: Urolithins, gut microbiota metabolites derived from ellagic acid and ellagitannins, reach micromolar concentrations in the colon lumen where can have anti-inflammatory and anticancer effects. The antiproliferative activity of urolithins (Uro-A, Uro-B, Uro-C and Uro-D) and their most relevant in vivo glucuronides were evaluated in three human colon cancer cell lines (Caco-2, SW480 and HT-29). Methods: Cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and Trypan blue exclusion assays. Cell cycle was evaluated by flow cytometry and urolithins metabolism by HPLC-MS/MS. Results: Urolithins inhibited cell proliferation and cell cycle progression in a time- and dose-dependent manner and arrested the cells at S and G2/M phases, depending on the urolithin. Uro-A exerted the highest antiproliferative activity, followed by Uro-C, Uro-D and Uro-B. Unlike Caco-2 and SW480 cells, HT-29 cells partially overcame the effects after 48 h, which was related to the complete glucuronidation of urolithins. Uro-A or Uro-B glucuronides did not affect cell cycle and showed lower antiproliferative activity than their aglycone counterparts. Uro-A or Uro-B plus inhibitors of drug efflux ABC transporters partially prevented the glucuronidation of urolithins in HT-29 cells which became more sensitive. Conclusions: Uro-A, Uro-B, Uro-C and Uro-D exerted different antiproliferative effects depending on the colon cancer cell line. We also report here, for the first time, the role of ABC transporters and Phase-II metabolism in HT-29 cells as a mechanism of cancer resistance against urolithins due to their conversion to glucuronide conjugates that exerted lower antiproliferative activity. © 2013 Springer-Verlag Berlin Heidelberg.


Gomez-Lopez V.M.,Research Group on Quality | Marin A.,Research Group on Quality | Allende A.,Research Group on Quality | Beuchat L.R.,University of Georgia | Gil M.I.,Research Group on Quality
Journal of Food Protection | Year: 2013

Internalization of foodborne pathogens in fruits and vegetables is an increasing safety concern. The aim of this research was to assess the potential for internalization of an enteric pathogen (Salmonella enterica serotype Typhimurium) in a leafy vegetable (baby spinach) during washing as influenced by three postharvest handling conditions: (i) illumination, (ii) negative temperature differential, and (iii) relative humidity (RH). To compare these potential postharvest handling conditions, leaves were exposed to different levels of illumination (0, 1,000, and 2,000 lx), temperature differential (5, 11, 14, 20, and 26uC), and RH (99, 85, and 74%) for a short time before or during washing. Washing of baby spinach was carried out in water containing green fluorescent protein-tagged Salmonella Typhimurium (6.5 log CFU/ml) at 5uC for 2 min, followed by surface disinfection with chlorine (10,000 mg/ml) for 1 min, two rinses in water for 10 s, and spin drying for 15 s. Internalization was assessed by enumerating the pathogen on Salmonella-Shigella agar and by confocal laser scanning microscopy. Illumination of spinach leaves before and during washing and a negative temperature differential during washing did not significantly (P . 0.05) increase the number of internalized bacteria. However, exposure of leaves to low-RH conditions before washing, which reduced the tissue water content, decreased internalization of Salmonella compared with internalization in baby spinach exposed to high RH (P # 0.05). Green fluorescent protein-tagged Salmonella Typhimurium was visualized by confocal laser scanning microscopy at a depth of up to 30 mm beneath the surface of spinach leaves after exposure to a high inoculum level (8 log CFU/ml) for an extended time (2 h). Results show that internalization of Salmonella into baby spinach leaves can occur but can be minimized under specific postharvest handling conditions such as low RH. Copyright ©, International Association for Food Protection.


Azorin-Ortuno M.,Research Group on Quality | Yanez-Gascon M.J.,Research Group on Quality | Pallares F.J.,University of Murcia | Vallejo F.,Research Group on Quality | And 4 more authors.
Journal of Agricultural and Food Chemistry | Year: 2010

A number of pharmacokinetic studies have shown marked differences in the plasma metabolic profile of resveratrol (RES) between humans and animals and between individuals of the same species, which complicates the identification of the putative bioactive metabolites responsible for the beneficial effects of RES. On the basis of the physiological similarity between pigs and humans, the aim of this work was to characterize the metabolic profile and pharmacokinetics of RES in the plasma of pigs and to compare this to values reported in humans. RES (5.9 mg/kg of body weight) was orally administered to pigs. The following metabolites were identified in plasma using HPLCMS/ MS: RES-diglucuronide (1), two isomers of RES-sulfoglucuronide (2, 3), two isomers of RESglucuronide (4, 5), RES-sulfate (6), and RES. The most abundant metabolites were 2, 5 (identified as resveratrol 3-O-glucuronide), and 6. The tmax ranged from 0.9 h for compounds 2 and 5 to 2 h for compound 3. The highest C max value was 2223 ng/mL (5.5 μM) for metabolite 5, which was 2.6-, 3.3-, and 12-fold higher than that for metabolites 6, 2, and 3, respectively. Peak plasma levels of RES (53 ng/mL; 0.23 μM) were detected 0.5 h after RES ingestion. Apart from the low levels of RES aglycone, the RES metabolic profile in pigs differs from that found in humans. The identification of the actual active RES metabolites is a challenge that requires more complex studies which should take into account many possible influencing factors such as age, gender, and methodological approaches. ©2010 American Chemical Society.

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