Papers by Begoña Muguerza
Milchwissenschaft
ABSTRACT
Ann Nutr Metab 2013;62(suppl 2):1-90 66 diometabolic abnormality was significantly and negatively... more Ann Nutr Metab 2013;62(suppl 2):1-90 66 diometabolic abnormality was significantly and negatively associated with physical activity level, education level, alcohol intake and olive oil intake and positively associated with BMI.
Background and Objectives: Flavanols are a cass of dietary phenolic compounds abundant in Mediter... more Background and Objectives: Flavanols are a cass of dietary phenolic compounds abundant in Mediterranean diet, with a well-defined biological activity and health benefits. However, their bioactive compounds responsible of the in vivo activity are still not well defined, and its identification and quantification are becoming important issues for the understanding of how polyphenols exert their beneficial effects. The low molecular weight forms of dietary flavanols are absorbed into the small intestine, and they are posteriorly conjugated in the intestine and liver to give sulphated, glucoronidated and/or methylated derivatives. The non-absorbed flavanols reach the colon where they are subjected to the microbiota metabolism and converted into small phenolic compounds which are efficiently absorbed in situ. The aim of this study was to identify the plasma colonic metabolites after an acute administration of a grape seed extract rich in flavanols. Methods: 1 g/kg of a grape seed extract ...
Flavan-3-ols and their oligomeric forms proanthocyanidins (PAs) are the most abundant polyphenols... more Flavan-3-ols and their oligomeric forms proanthocyanidins (PAs) are the most abundant polyphenols in the human diet and, as with other polyphenols, they exert several beneficial health effects in vivo. Dietary PAs are poorly absorbed in the small intestine and reach the colon where gut bacteria enzymes can hydrolize them and break down the polyphenolic skeleton to get small molecular metabolites which can reach systemic circulation. However, the PAs microbial metabolisation has been poorly described in in vivo studies. The aim of this study was to determine the colonic biotransformation pathway of grape seed PAs in rat plasma after an acute administration of a grape seed PA extract (GSPE). For this, rat plasma flavonoids and their colonic metabolites were analysed by HPLC-MS/MS at 2, 4, 7, 24 and 48 h after the ingestion of GSPE (1000 mg/kg). Results showed that non-metabolised flavanols peak plasma concentrations at 2 h after GSPE administration, whereas the colonic metabolites app...
Antihypertensive effects of grape seed polyphenols have been reported. This beneficial effect has... more Antihypertensive effects of grape seed polyphenols have been reported. This beneficial effect has been attributed to an enhancement of the availability of vasodilatory factor nitric oxide (NO). In the present study, mRNA levels of different genes implicated in endothelial dysfunction (ED), characteristic of many pathologies such as hypertension (HPT), have been studied in hypertensive cafeteria (CAF) fed rats. Twenty-four rats fed CAF diet for 18 weeks were acutely intragastrically administered water or 375 mg/kg of a grape seed extract rich in low molecular weight polyphenols (LM-GSPE) and sacrificed 6 hours post-administration. Blood pressure was recorded before administration and just before sacrifice. Aorta gene expression was performed for endothelial NO synthase (eNOS), arginase 1, Krüppel-like factor 2 (KLF2), sirtuin 1 (Sirt1), ET-1, angiotensin II receptor type 1 a and b (ART1a, ART1b) and NADPH oxygenase 4 (NOX-4). Antihypertensive effect was verified for CAF fed rats trea...
Food Funct., 2015
We studied the short-term antihypertensive effect of flavan-3-ols (−)-epicatechin, (+)-catechin a... more We studied the short-term antihypertensive effect of flavan-3-ols (−)-epicatechin, (+)-catechin and (−)-catechin, in spontaneously hypertensive rats (SHR). Plasma metabolites and the corresponding plasma antioxidant capacity were determined. All the assayed flavan-3-ols decreased systolic blood pressure (SBP) in SHR. Their antihypertensive effects were less pronounced than that of Captopril (50 mg kg −1 ) and
Once consumed, flavanols are recognised as xenobiotics and conjugated in the small intestine and ... more Once consumed, flavanols are recognised as xenobiotics and conjugated in the small intestine and liver as their glucuronide, sulphate and methylated forms to go to systemic circulation and further distribute around the body 1,2 . However, the intake of large amounts of polyphenolrich products is not directly linked to the concentration of these compounds in blood and tissues 3,4 . Hence, the main objective of this study was to evaluate how flavanols and their metabolites are distributed around the body after the intake of different doses of grape seed polyphenol extract (GSPE). !
La enfermedad cardiovascular es la principal causa de muerte en el mundo y la hipertensión arteri... more La enfermedad cardiovascular es la principal causa de muerte en el mundo y la hipertensión arterial es uno de sus principales factores de riesgo. Varios estudios han demostrado que el consumo de alimentos o ingredientes ricos en flavanoles, como el cacao o extracto de pepita de uva, mejoran la función endotelial y disminuyen la presión arterial. Diferentes mecanismos podrían justificar las propiedades antihipertensivas de los flavanoles. La vasodilatación ocasionada por estos compuestos se ha relacionado con la reducción del estrés oxidativo, con la producción de óxido nítrico (NO) y la inhibición de la enzima convertidora de la angiotensina (ECA), clave para el control de la presión arterial. El cacao y el extracto de pepita de uva son productos ricos en flavanoles del tipo flavan-3-ol y proantocianidinas que han demostrado gran actividad antioxidante. Sin embargo, la concentración real de flavonoides que alcanzan los vasos sanguineos es tan baja que es poco probable que estos comp...
The Journal of Nutritional Biochemistry, 2015
Flavanols are metabolized in the small intestine and the liver to produce their glucuronidated, s... more Flavanols are metabolized in the small intestine and the liver to produce their glucuronidated, sulfated or methylated conjugates that can be body distributed or excreted in the urine. However, the intake of large amounts of flavanols is not directly related to their bioavailability. This study aims to investigate the administered dose dependence of flavanols' conjugation and body distribution. In this study, different doses of a grape seed proanthocyanidin extract (GSPE; 125, 250, 375 and 1000 mg/kg) were orally administered to male Wistar rats. Tissues were collected 2 h after GSPE administration. Flavanols were quantified by HPLC-MS/MS. Results show that the majority of GSPE metabolites are located in the kidney, followed by the liver. Lower concentrations were found in mesenteric white adipose tissue (MWAT) and the brain. Moreover, flavanol metabolites followed a tissue-specific distribution pattern independent of dosage. In the kidney, glucuronidated metabolites were the most abundant; however, in the liver, it was mainly methyl-glucuronidated metabolites. In MWAT, free flavanols were dominant, and methylated metabolites were dominant in the brain. Concentration within a tissue was dependent on the administered dose. In conclusion, flavanol metabolites follow a tissue-specific distribution pattern and only the tissue concentration of flavanol metabolites is dependent on the administered dose.
Metabolic syndrome (MS) is a combination of medical disorders such as hypertension, dyslipidaemia... more Metabolic syndrome (MS) is a combination of medical disorders such as hypertension, dyslipidaemia and obesity that, when occurring together, increase the risk of developing cardiovascular and diabetes. Our group, have demonstrated that a grape seed procyanidin extract (GSPE) exhibit different beneficial properties on various parameters related to MS. The aim of this study was to evaluate the effects of GSPE in blood pressure (BP) and to study the potential antihypertensive mechanisms involved. Male spontaneously hypertensive rats (SHR) (17-20-week-old) were administered by gastric intubation water or 250, 375 and 500 mg/Kg GSPE (minimum n=8 per group). Captopril (50 mg/Kg), a known antihypertensive drug, was used as a positive control (n=8). Systolic and diastolic blood pressure (SBP and DBP) were recorded in the rats by the tail cuff method initially and 2, 4, 6, 8, 24, and 48 h post-administration. To determine the mechanisms involved, 2 groups of 15 animals were administered by i...
European Journal of Nutrition, 2015
effect was completely abolished by l-NAME and partially inhibited by indomethacin. Conclusions GS... more effect was completely abolished by l-NAME and partially inhibited by indomethacin. Conclusions GSPE acts as an antihypertensive agent in a rat model of hypertension associated with MS. The change in endothelium-derived NO availability is one of the mechanisms involved in the antihypertensive effect of GSPE in CHRs. Additionally, endothelial prostacyclin contributes to the effect of GSPE on arterial BP.
Hipertensión, 2006
[Introducción y objetivos] La fermentación de la leche por algunas bacterias genera péptidos con ... more [Introducción y objetivos] La fermentación de la leche por algunas bacterias genera péptidos con actividad inhibidora de la enzima convertidora de la angiotensina. Se evalúan los cambios de la presión arterial que produce en ratas espontáneamente hipertensas la ...
Journal of Dairy Science, 2006
Among different lactic acid bacteria isolated from raw milk, 4 Enterococcus faecalis strains have... more Among different lactic acid bacteria isolated from raw milk, 4 Enterococcus faecalis strains have stood out as producers of fermented milk with potent antihypertensive activity. The peptide β-casein f(133-138), LHLPLP, was identified as one of the major peptides responsible for the activity of these fermented milk products. A simple method was developed to quantify this peptide in fermented milk using high-performance liquid chromatography coupled in line with mass spectrometry. This procedure does not require any previous sample fractionation or extraction, and direct analysis of the watersoluble extract obtained from the fermented milk can be performed. Validation studies showed sufficient specificity, reproducibility, linearity, and recovery, demonstrating that this method can be used for the routine quantification of LHLPLP during the production of fermented milk products. The developed method was readily applied to quantify the peptide LHLPLP under different fermentation conditions and with different aromatized products.
The Journal of Nutritional Biochemistry, 2015
Physiological concentrations (1 μM) of 15 flavonoids were evaluated in human umbilical vein endot... more Physiological concentrations (1 μM) of 15 flavonoids were evaluated in human umbilical vein endothelial cells in the presence of hydrogen peroxide (H 2 O 2 ) for their ability to affect endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) expression in order to establish the structural basis of their bioactivity. Flavonoid effects on eNOS transcription factor Krüpple like factor-2 (KLF-2) expression were also evaluated. All studied flavonoids appeared to be effective compounds for counteracting the oxidative stress-induced effects on vascular gene expression, indicating that flavonoids are an excellent source of functional endothelial regulator products. Notably, the more effective flavonoids for KLF-2 up-regulation resulted in the highest values for eNOS expression, showing that the increment of eNOS expression would take place through KLF-2 induction. Structure-activity relationship studies showed that the combinations of substructures on flavonoid skeleton that regulate eNOS expression are made up of the following elements: glycosylation and hydroxylation of C-ring, double bond C2_C3 at C-ring, methoxylation and hydroxylation of B-ring, ketone group in C4 at C-ring and glycosylation in C7 of A-ring, while flavonoid features involved in the reduction of vasoconstrictor ET-1 expression are as follows: double bond C2_C3 at C-ring glycosylation in C7 of A-ring and ketone group in C4 of C-ring.
Food Research International, 2014
Hyperlipidemia is one of the principal causes of cardiovascular disease and proanthocyanidins (PA... more Hyperlipidemia is one of the principal causes of cardiovascular disease and proanthocyanidins (PAs) regulate lipid homeostasis. This study aims to evaluate the concentration of PAs in rat serum after the administration of different doses of PAs and to determine the capacity of these metabolites to reduce de novolipid synthesis in HepG2 cells. Two hours after oral administration of different doses of a grape seed proanthocyanidin extract (GSPE) (1000, 375, 250 and 125 mg/kg), serum was semi-purified and characterised by HPLC-ESI-MS/MS before analysing the synthesis and secretion of lipids in HepG2 cells. Results showed a dose-dependent appearance of metabolised PAs in serum at doses up to 375 mg/kg and saturation at 1000 mg/kg of GSPE. A reduction in cholesterol esters (CE), free cholesterol (FC) and triglycerides (TG) synthesis was observed without dose-dependence when the cells were treated with PAs metabolites. Moreover, a low dose of metabolites (125 mg/kg) was sufficient to reduce FC and TG synthesis. In conclusion, the study demonstrated that PAs metabolise in a dose-dependent manner up to 370 mg/kg but not dose-dependent effect was shown in reducing the de novosynthesis of lipids.
Revista Brasileira de Medicina do Esporte, 2008
OBJECTIVE: To verify the influence of dietary antioxidant supplementation in older women who regu... more OBJECTIVE: To verify the influence of dietary antioxidant supplementation in older women who regularly practice physical activities, on the occurrence of oxidative stress, physical health and risk of cardiovascular diseases (CVD). METHOD: Two groups (S and C) of women, with age ranging from 60 to 80 years old, were observed. Both groups took part in a physical activity program for 58 weeks, three times a week, for about 50 to 55 minutes each session. The diet of group S (n=36) was daily supplemented with 330 ml of a functional antioxidant beverage, FuncionaTM; Group C (n=32) ingested water and was used as Control. As oxidative stress indicators, the plasmatic concentrations of reduced (GSH) and oxidized (GSSG) glutathione were determined; the molar GSH/GSSG ratio was calculated, and the oxidative damage in lipids and proteins was evaluated. The physical and cardiovascular conditions were evaluated through routine anthropometric parameters (weight, stature and BMI) and blood pressure. RESULTS: Group C presented significant increases of oxidative stress, reduction in the blood pressure and in the indicators of cardiovascular risks. Group S presented significant reduction of the oxidative stress and increment of the cardiovascular gains. Significance concerning the ergogenic effects has not been identified. CONCLUSION: Our data suggest that regular exercise in older women can improve physical and cardiovascular conditions. Moreover, daily intake of functional antioxidant supplement can minimize harmful effects of the reactive oxygen species.
Journal of Functional Foods, 2015
Flavan-3-ols and their oligomeric forms, proanthocyanidins (PAs), are poorly absorbed in the smal... more Flavan-3-ols and their oligomeric forms, proanthocyanidins (PAs), are poorly absorbed in the small intestine and reach the colon where gut bacteria enzymes can hydrolyse them to produce small molecular metabolites, which can reach systemic circulation. However, the microbial metabolism of flavanols has been poorly described in vivo. The aim of this study was to determine the colonic biotransformation pathway and the plasma temporal appearance of grape seed flavanols colonic metabolites in rats. Rat plasma colonic metabolites were analysed by HPLC-MS/MS at 2, 7, 24 and 48 h after 1000 mg/kg of a grape seed PA extract (GSPE) administration. Results indicated that non-metabolised flavanols have peak plasma concentrations 2 h after GSPE administration, whereas the colonic metabolites appeared in plasma later, indicating their gradual colonic biotransformation as valerolactone > phenylpropionic acids ≈ phenylacetic acids > benzoic acids. This study shows how flavanols are biotransformed by gut bacteria in rats over time, facilitating potential bioactive compound identification for particular health effects.
Journal of Agricultural and Food Chemistry, 2014
This study describes the development and validation of a liquid chromatography−mass spectrometry ... more This study describes the development and validation of a liquid chromatography−mass spectrometry method for determination of a large number of flavanol colonic derivatives in biological samples. The method was validated with rat plasma after the intake of grape seed flavanols. The minimum plasma volume necessary to maintain good recovery values within the range of 83−110% for all of the standards was determined by micro solid-phase extraction (μ-SPE). In total, 16 commercial standards were used to measure 30 different phenolic compounds present at low concentration levels (micromolar). The chromatographic method enabled reliable quantification of plasma colonic flavanol derivatives with low limits of detection and quantification, achieving values of 0.03 nM and 0.10 nM, respectively. The developed method can be readily applied to determine all of the flavanol metabolites that are most likely responsible for the majority of biological effects of poorly absorbed flavanols.
Food & Function, 2014
We have previously reported that procyanidins, a class of flavonoids, improve glycemia and exert ... more We have previously reported that procyanidins, a class of flavonoids, improve glycemia and exert an incretin-like effect, which was linked to their proven inhibitory effect on the dipeptidyl-peptidase 4 (DPP4) activity. However, their actual effect on incretin levels has not been reported yet. Therefore, in the present study we have evaluated whether a grape seed extract enriched in procyanidins (GSPE) modulates plasma incretin levels and attempted to determine the mechanisms involved. An acute GSPE treatment in healthy Wistar female rats prior to an oral glucose load induced an increase in plasma active glucagon-like peptide-1 (GLP-1), which was accompanied by an increase in the plasma insulin/glucose ratio and a simultaneous decrease in glucose levels. In agreement with our previous studies, the intestinal DPP4 activity was inhibited by the GSPE treatment. We have also assayed in vitro whether this inhibition occurs in inner intestinal tissues close to GLP-1-producing cells, such as the endothelium of the capillaries. We have found that the main compounds absorbed by intestinal CaCo-2 cells after an acute treatment with GSPE are catechin, epicatechin, B2 dimer and gallic acid, and that they inhibit the DPP4 activity in endothelial HUVEC cells in an additive way. Moreover, an increase in plasma total GLP-1 levels was found, suggesting an increase in GLP-1 secretion. In conclusion, our results show that GSPE improves glycemia through its action on GLP-1 secretion and on the inhibition of the inner intestinal DPP4 activity, leading to an increase in active GLP-1 levels, which, in turn, may affect the insulin release.
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Papers by Begoña Muguerza