Amaya Aleixandre

Complutense University of Madrid, Madrid, Madrid, Spain

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Publications (54)115.03 Total impact

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    ABSTRACT: Three citrus fruit extracts (orange, grapefruit and lemon), an olive leaf extract and a citrus–olive mixed extract (Citrolive), which was obtained from olive leaf and bitter orange fruits, were characterized by HPLC and investigated for their endothelium-dependent vascular relaxing ability. Subsequently, aorta rings from SHR were mounted in tissue baths. They were pre-contracted with methoxamine and exposed to the extracts. Intact, endothelium-denuded, L-NAME-, indomethacin- and sirtinol-treated preparations were used. All extracts exhibited endothelium-dependent relaxations that were totally reversed by L-NAME and partly blocked by sirtinol. Indomethacin also decreased the relaxing effect of high doses of lemon and olive extracts, but the arterial relaxations caused by low doses of the different extracts and those caused by high doses of Citrolive extract (a mixed extract) were potentiated by indomethacin. This study confirms Mediterranean plants as an excellent source of functional compounds, showing the relaxing effect of the assayed plant extracts in aorta rings from SHR. Moreover, the results obtained demonstrate the endothelium-dependent vascular relaxing effect of the studied extracts. Endothelial NO release seems implicated in the effect of all extracts and prostacyclin probably participates in the effect of lemon and olive extracts. Nevertheless, enhanced vasoconstrictor endoperoxides seem to be of special importance in the endothelial tissue of SHR, and the release of these products may impair, at least in part, the endothelium-dependent vascular relaxation caused in these animals by orange, grapefruit, lemon, olive, and in particular, Citrolive extracts.
    Full-text · Article · Sep 2015 · Food Research International
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    ABSTRACT: We study the short-term antihypertensive effect of the 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) and were not shown in normotensive Wistar-Kyoto rats. 6 mg/kg (-)-epicatechin caused the maximum decrease in SBP. The maximum effects of the catechin monomers were observed post-administration of 0.5 mg/kg of that flavan-3-ols, being (-)-catechin the least effective among the three assayed compounds. Glucuronide and methyl glucuronide metabolites were obtained in the flavan-3-ol treated SHR, but it was not possible to relate the antihypertensive effect of the assayed flavan-3-ols with a concrete plasma metabolite or with their antioxidant effect. In conclusion, the studied flavan-3-ols could be responsible for the antihypertensive effect of cocoa products.
    Full-text · Article · Aug 2015 · Food & Function
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    ABSTRACT: The aim of this study was to evaluate the involvement of endothelial-relaxing factors as possible antihypertensive mechanism of low-molecular-weight procyanidin rich grape seed extract (LM-GSPE). Thirty 17–20-week-old male spontaneously hypertensive rats (SHR) were administered water or 375 mg/kg LM-GSPE by intragastric gavage. One millilitre of saline, 30 mg/kg NG-Nitro-l-arginine methyl ester (l-NAME) or 5 mg/kg indomethacin was administrated intraperitoneally. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded before and 6 h after oral administration. Plasma concentration of 6-keto-prostaglandin F1α (PGF1α) was quantified. In addition, we evaluated the relaxation caused by LM-GSPE in different aorta preparations. The antihypertensive effect of LM-GSPE was completely and partially abolished by l-NAME and indomethacin, respectively. In addition, plasma PGF1α was increased in LM-GSPE-administered rats. Finally, LM-GSPE relaxed the intact aorta preparations but did not relax the endothelium-denuded aorta rings. l-NAME inhibited the relaxation caused by LM-GSPE in the SHR aorta rings, but indomethacin did not. Therefore, the antihypertensive effect of LM-GSPE in SHR is endothelium dependent, and it could be mediated by changes in endothelium-derived nitric oxide bioavailability. Nevertheless, prostacyclin could also contribute additionally to this effect.
    Full-text · Article · Jan 2014 · Journal of Functional Foods
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    ABSTRACT: We evaluate the short-term effect of a Fraxinus excelsior L. seed extract, named FraxiPure (FRP) on spontaneously hypertensive rats (SHR). Water, Captopril and different doses of FRP were orally administered. Blood pressure was recorded by the tail cuff method and plasma samples were collected to determine antioxidant capacity and malondialdehyde equivalents. In other trials, 18 h fasted SHR were administered water, FRP, Furosemide, Torasemide, and Captopril. In these animals, urine was collected for 4 h to obtain the urine volumetric excretion (UVE). Plasma samples of these animals were used to establish the fractional excretion (FE) of different ions (Na+, Cl−, K+, Ca2 + and PO43 −) and metabolites (creatinine, urea and uric acid).FRP shows antihypertensive effect. The decrease in blood pressure caused by FRP was slightly lower than that of Captopril and more accentuated than that of Torasemide. FRP and Torasemide significantly increased UVE. Torasemide significantly increased FE(Na+) and FE(Cl−) and showed a clear uricosuric effect. FRP showed slight natriuretic effects and behaved as a potassium-sparing diuretic. FRP significantly increased plasma antioxidant capacity and decreased plasma malondialdehyde equivalents. The antihypertensive effect of FRP in SHR can therefore be related with its diuretic and antioxidant properties.
    Preview · Article · Aug 2013 · International Journal of Hypertension
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    M. Quiñones · L. Guerrero · M. Suarez · Z. Pons · A. Aleixandre · L. Arola · B. Muguerza
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    ABSTRACT: Abstract Grapes are a good source of flavonoids, which have been previously demonstrated to exert beneficial healthy effects on cardiovascular diseases. The aims of this study were to extensively characterise a grape seed procyanidin extract (GSPE) (total phenolic content, antioxidant capacity and HPLC–MS phenolic profile) and, to assess its antihypertensive effect in spontaneously hypertensive rats (SHR) which is a model of genetically hypertensive rat analogue to the essential hypertension in humans. The hypotensive effect of GSPE was also proved in normotensive Wistar–Kyoto rats. Chromatographic analysis of the extract showed that the most abundant polyphenols are monomers and dimers, in their free forms and linked to a gallate. GSPE produced a significant decrease in systolic and diastolic blood pressure of SHR dose-dependently up to 375 mg/kg (maximum decrease 6 h post-administration) and did not affect blood pressure of Wistar–Kyoto rats. GSPE increased the activity of an antioxidant endogen system, but did not affect plasma ACE activity in these animals.
    Full-text · Article · May 2013 · Food Research International
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    ABSTRACT: The involvement of endothelial-relaxing factors on the vascular and antihypertensive effects of a cocoa fiber product (CFP) obtained from cocoa husks was studied. We carried out in vitro experiments with aorta rings from untreated spontaneously hypertensive rats (SHR) and in vivo experiments with SHR. CFP did not relax the endothelium denuded aorta rings and N(W)-nitro-L-arginine methyl ester (L-NAME) partially blocked the vascular relaxing and antihypertensive effects of CFP. Nevertheless, indomethacin did not modify these effects. Nitric oxide mediates therefore the antihypertensive and aorta relaxing effects of CFP in SHR.
    No preview · Article · Nov 2012 · Nitric Oxide
  • M Quiñones · M Miguel · A Aleixandre
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    ABSTRACT: In recent years, a number of studies have endorsed the beneficial effects of polyphenols intake on health, especially on the cardiovascular system. This is important since cardiovascular diseases are the main death cause worldwide. The effects of polyphenols are mainly due to their antioxidant properties. These compounds present vasodilating effects, and they can improve the lipid profile and lessen the oxidation of low-density lipoproteins (LDL). They show clear antiinflammatory effects and they can modulate the apoptotic pathways in the vascular endothelium. This review defines from the structural viewpoint the different groups of polyphenols that may occur in vegetables, and updates the knowledge on their bioavailability. Some of the recent studies establishing their beneficial properties at a cardiovascular level are also included.
    No preview · Article · Feb 2012 · Nutricion hospitalaria: organo oficial de la Sociedad Espanola de Nutricion Parenteral y Enteral
  • M. Quiñones · M. Miguel · A. Aleixandre
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    ABSTRACT: In recent years, a number of studies have endorsed the beneficial effects of polyphenols intake on health, especially on the cardiovascular system. This is important since cardiovascular diseases are the main death cause worldwide. The effects of polyphenols are mainly due to their antioxidant properties. These compounds present vasodilating effects, and they can improve the lipid profile and lessen the oxidation of low-density lipoproteins (LDL). They show clear antiinflammatory effects and they can modulate the apoptotic pathways in the vascular endothelium. This review defines from the structural viewpoint the different groups of polyphenols that may occur in vegetables, and updates the knowledge on their bioavailability. Some of the recent studies establishing their beneficial properties at a cardiovascular level are also included.
    No preview · Article · Feb 2012 · Nutricion hospitalaria: organo oficial de la Sociedad Espanola de Nutricion Parenteral y Enteral
  • N. López Carreras · M. Miguel · A. Aleixandre
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    ABSTRACT: Food components can have biological activity and healthy properties. Some of them, produced by plants, are named phytochemicals. The diversity of phytochemicals is amazing and this term refers in fact to a wide variety of compounds. Some of them, biosynthesized from isoprene, are named terpenes, and an important group of biciclic monoterpenes, derived from geraniol, are named iridoids. Iridoids can have open structures (secoiridoids) or closed structures (really iridoids) and they appear usua lly as heteroside compounds, in particular as glycosides. They have beneficial effects on liver and bi - liary function. Moreover, they have also demonstrated anti-inflammatory, antibacterial, anti-carcinogenic and antiviral activity, and they can be used as antidote in mushroom intoxications, in particular, those caused by Amanita type. Iridoids are present in particular in plants such as olive, harpagophytum, the valerian plant, the gentian plant and the ash tree. All these plants have been reported to be used as traditional medicine in many cultures. Nowadays, their leaves, tubercles, roots, seeds, and extracts are also considered important for pharmacology, and some of their active compounds have been identified. This review refers to the origin and biosynthetic pathways of iridoids. It des - cribes the characteristics and properties of the plants mentioned above, and it also mentions the principal iridoids isolated from them.
    No preview · Article · Jan 2012 · Nutricion Clinica y Dietetica Hospitalaria
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    David Sánchez · Marta Miguel · Amaya Aleixandre
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    ABSTRACT: The consumption of dietary fiber (DF) has increased since it was related to the prevention of a range of illnesses and pathological conditions. DF can modify some gut hormones that regulate satiety and energy intake, thus also affecting lipid metabolism and energy expenditure. Among these gut hormones are ghrelin, glucagon-like peptide 1, peptide YY, and cholecystokinin. Adipose tissue is known to express and secrete a variety of products known as "adipocytokines," which are also affected by DF. Some of the most relevant adipocytokines include adiponectin, leptin, tumor necrosis factor-α, and interleukin-6. The release of adipocytokines, by either adipocytes or macrophage-infiltrated adipose tissue, leads to a chronic subinflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes, therefore increasing the risk of cardiovascular disease associated with obesity. DF modulation of these molecules could also have positive effects on obesity, insulin resistance, and hyperlipidemia. This review is focused on the effects of DF on the above-mentioned gut peptides and adipocytokines.
    Preview · Article · Dec 2011 · Journal of medicinal food
  • Amaya Aleixandre · Marta Miguel

    No preview · Chapter · Dec 2011
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    M Quiñones · M Miguel · B Muguerza · A Aleixandre
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    ABSTRACT: In this study, we evaluated the short-term effect of a cocoa polyphenol extract (CPE), in spontaneously hypertensive rats (SHR). Male 17-22-week-old SHR were administered by intragastric gavage water, 50 mg kg(-1) Captopril or CPE at different doses (13, 26, 80 and 160 mg kg(-1)). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded by the tail cuff method before the administration and also 2, 4, 6, 8, 24, 48 and 72 h post-administration. Highly significant decreases in the SBP and in the DBP were observed when captopril or CPE was administered to SHR. The cocoa extract produced a dose dependent effect in the SBP of the SHR up to the dose of 80 mg kg(-1). Nevertheless this dose of CPE did not decrease the arterial blood pressure in the normotensive Wistar Kyoto rats. The decrease in the SBP caused by 80 mg kg(-1) of CPE in the SHR (-39.1 ± 3.7 mm Hg) was maximum 6 h post-administration, and the initial values of SBP were recovered 72 h post-administration of this extract. Paradoxically, 160 mg kg(-1) of the cocoa extract caused a decreased antihypertensive effect than lower doses of CPE. In addition, the decrease in DBP was always more accentuated when the dose of CPE administered was lower. Our results suggest that CPE may be used as a functional food ingredient with beneficial effects for controlling arterial blood pressure.
    Full-text · Article · Nov 2011 · Food & Function
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    M Quiñones · B Muguerza · M Miguel · A Aleixandre
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    ABSTRACT: The involvement of endothelial-relaxing factors on the antihypertensive effect of a polyphenol-rich cocoa powder named CocoanOX (CCX) was studied. Thirty 17-20-week-old male spontaneously hypertensive rats (SHR), weighing 314 ± 3g were used. They were divided into two groups of 15 animals, that were respectively administered by gastric intubation distilled water or 300 mg/kg CCX dissolved in distilled water, between 9 am and 10 am. 2h after the oral administration, 5 of the animals in each group were intraperitoneally administered 1 ml saline. The remaining rats in both groups were divided into another two groups of 5 animals that were respectively administered 30 mg/kg Nw-nitro-L-arginine methyl ester (L-NAME) dissolved in 1 ml of saline or 5 mg/kg indomethacin also dissolved in 1 ml of saline by the same procedure. Systolic blood pressure (SBP) was recorded in the rats by the tail cuff method before the initial oral administration and also 4h after this administration. CCX caused a significant decrease in SBP (-49.5 ± 4.9 mmHg; p<0.05). L-NAME caused a clear increase in SBP in the rats (+16.2 ± 4.3 mmHg; p<0.05), and the effect of CCX was not observed in the SHR that were treated with L-NAME (+4.1 ± 1.7 mmHg; p<0.05). Nevertheless, indomethacin treatment did not modify SBP in the SHR and this compound failed to modify the antihypertensive effect of CCX in these animals. In conclusion, this study proves the participation of NO in the antihypertensive effect of CCX in the SHR strain. When CCX is administered, the synthesis, or the bioavailability, of this endothelial factor could increase, but other mechanisms may also participate in the antihypertensive effect of this cocoa powder. In any case, further investigation should be carried out to characterize the signalling pathways involved in the antihypertensive effect of CCX.
    Full-text · Article · Jun 2011 · Pharmacological Research
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    ABSTRACT: We investigate the mechanisms involved in the long-term antihypertensive effect of a polyphenol-rich cocoa powder, named CocoanOX® (CCX), in spontaneously hypertensive rats (SHR). We have carried out two different batches of experiments. For the first batch of experiments, forty 3 week-old male SHR were randomly divided with ad libitum intake into four groups of 10 animals, that respectively received the following drinking fluids up to the 20th week of life (treatment period): tap water (control), CCX 100 mg/kg/day, CCX 200 mg/kg/day and CCX 400 mg/kg/day. Five 20 week-old rats of each group were sacrificed by decapitation. From the 20th to 24th week of life all the remaining animals were given tap water (follow-up period), and all of them were sacrificed at the end of the follow-up period. Plasma malondialdehyde (MDA), reduced glutathione in the liver, plasma and aorta angiotensin converting enzyme (ACE) activity and plasma angiotensin II were determined in all the sacrificed SHR that were included in this batch of experiments. Plasma MDA decreased and liver reduced glutathione increased in the 20 week-old CCX treated SHR. These effects were not observed in the rats that were sacrificed after the follow-up period. CCX treatment did not modify aorta ACE activity, but the activity of ACE and the levels of angiotensin II increased in the plasma of the SHR treated with the highest dose of CCX. ACE activity returned to basal values in the SHR that were sacrificed after the follow-up period. However, angiotensin II levels were slightly higher after withdrawal of CCX.
    Full-text · Article · Jun 2011 · Food Research International
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    ABSTRACT: In this study we evaluated the effect of the administration of different soluble fiber enriched-diets on inflammatory and redox state of Zucker fatty rats. Four groups of ten 8 week-old female Zucker fatty rats were used. The four groups were respectively fed the following diets until the 15th week of life: standard diet (obese control), 10% high methoxylated apple pectin (HMAP)-, 5% soluble cocoa fiber (SCF)-, and 10% β-glucan-enriched diets. A group of Zucker lean rats fed the standard diet was also used as control for normal values of this rat strain. The plasma levels of tumoral necrosis factor-α (TNF-α), adiponectin, and malondialdehyde (MDA) were measured at the end of treatment. The reduced glutathione liver levels were also obtained at that moment. TNF-α plasma levels decreased somewhat in Zucker fatty rats fed the different fibers, and MDA plasma levels significantly decreased in these animals. Nevertheless, adiponectin plasma levels increased in the Zucker fatty rats fed the SCF enriched diet, but did not change in the HMAP and the β-glucan group. The Zucker fatty rats fed the different fiber showed a trend towards increased the reduced glutathione liver levels, but significant differences with obese control rats were only obtained in the β-glucan group. The results obtained in this study suggest that the intake of the different soluble fiber-enriched diets that we have evaluated could prevent and/or attenuate the inflammatory and/or the prooxidative state of the metabolic syndrome.
    Full-text · Article · Feb 2011 · Pharmacological Research
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    ABSTRACT: We have evaluated the effect of the long-term intake of a cocoa powder, with high concentration of polyphenols, named CocoanOX (CCX), on the development of hypertension of spontaneously hypertensive rats (SHR). Systolic blood pressure was measured weekly in the rats, from the 6th to 24th week of life, by the tail cuff method. The development of hypertension was attenuated in the groups treated with captopril or CCX. The antihypertensive effect was more accentuated in the group treated with captopril, and it was paradoxically more accentuated in the group treated with the lowest dose of CCX than in the other CCX groups. The arterial blood pressure increased in the treated SHR when the corresponding antihypertensive treatment was removed. Both, CCX and the standard cocoa, improved the aorta endothelial function in the SHR. In conclusion, CCX could be used as a functional food ingredient with antihypertensive activity.
    Full-text · Article · Oct 2010 · Food Chemistry
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    ABSTRACT: In this study we evaluated the short-term oral antihypertensive effect of several peptide sequences isolated from casein fractions, previously characterized as in vitro angiotensin-converting enzyme-inhibitors, in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP) and the diastolic blood pressure (DBP) of the rats were measured by the tail cuff method before administration and also 2, 4, 6, 8 and 24 h post-administration. The sequences LVYPFTGPIPN, HLPLP, IAK, YAKPVA and WQVLPNAVPAK showed a clear decrease in SBP and DBP in SHR. HPHPHLSF caused a significant decrease of the DBP in the SHR, but this sequence did not modify the SBP of these animals in a significant manner. KKYNVPQL did not modify SBP in the SHR, and caused a slight, but significant and maintained, decrease in DBP in these animals. SBP and DBP returned to baseline values 24 h post-administration of all peptides. In conclusion, these peptides are bioactive ingredients with potential benefit in the prevention and treatment of hypertension or other associated disorders.
    No preview · Article · Oct 2010 · Molecular Nutrition & Food Research
  • D Sanchez · M Miguel · A Aleixandre
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    ABSTRACT: Endothelial dysfunction is one of the many proposed mechanisms of hypertension and it may justify, at least in part, the increased blood pressure of hypertensive subjects. Nevertheless, the exact mechanisms involved in the hypertensive condition of obese Zucker rats are unclear. In this study, we measured the arterial blood pressure (tail cuff method) of four groups of seven, female, obese Zucker rats each. The rats of groups 1-4 were 9-12, 15-18, 21-24 and 27-30 weeks old respectively. We also evaluated the responses of aortic rings to KCl, methoxamine and acetylcholine, in these animals. Aortic rings were successively exposed to 80 mM KCl and to methoxamine (10(-8)-10(-5) M). The endothelium-dependent relaxation to acetylcholine (10(-9)-10(-5) M) was also established in the methoxamine-precontracted tissue (precontraction close to 80% of the maximum effect of methoxamine). A clear increase in the arterial blood pressure was observed when the age of these animals increased. The contractile responses to KCl and methoxamine were lower in the aortic rings of rats with increased arterial blood pressure. The response to acetylcholine was lower in the rings from 15-18, 21-24 and 27-30 weeks old rats, than in the younger groups. In conclusion, obese Zucker rats develop hypertension and endothelial dysfunction. Nevertheless, the arterial contractions elicited by depolarization or by α(1)-adrenoceptor stimulation decrease in aged, obese Zucker rats.
    No preview · Article · Jul 2010 · Methods and Findings in Experimental and Clinical Pharmacology
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    ABSTRACT: Objetives: Cocoa polyphenols have shown antihypertensive effects. We investigate the mechanism involved in the antihypertensive effect of CocoanOX (CCX), a cocoa powder prepared by an industrial procedure to prevent polyphenol degradation. Design and Methods: Male 3-week-old spontaneously hypertensive rats (SHR) were divided into four groups of ten animals that were respectively long-term administered tap water (control), 100 mg/kg/day CCX, 200 mg/kg/day CCX or 400 mg/kg/day CCX. Five 20-week-old rats of each group were sacrificed and the different treatments were then removed in the remaining rats. Arterial blood pressure was weekly measured from the 6th to the 24th week of life in the SHR and all the rats were sacrificed at the end of the experimental period. The following measurements were performed in the sacrificed SHR: endothelium-dependent aorta relaxation to acetylcholine, plasma malonildialdehyde, angiotensin converting enzyme activity in plasma and aorta. Results: CCX improved in a dose-dependent manner acetylcholine relaxation in the aorta of the treated SHR. Plasma malonildialdehyde decreased in the CCX treated SHR. The effects mentioned before were not observed in the SHR after the withdrawal of CCX. CCX treatment did not modify aorta angiotensin converting enzyme activity, but the activity of this enzyme increased in the plasma of the SHR treated with the highest dose of CCX. Conclusion: The antihypertensive effect of CCX in SHR is mainly mediated by an improvement of endothelial function and by a reduction of oxidative stress.
    No preview · Article · Jun 2010 · Journal of Hypertension
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    ABSTRACT: The effects of a soluble cocoa fiber (SCF) were studied in Zucker fatty rats. Two groups of Zucker fatty rats were fed the following diets: standard diet and 5% SCF-enriched diet. A group of Zucker lean rats fed the standard diet was used for results comparison with obese Zucker animals. Solid and liquid intakes, body weight, plasma glucose, lipid profile, and systolic (SBP) and diastolic (DBP) blood pressure were recorded weekly. At the end of the experimental period insulin was determined, and fat apparent digestibility (FAD) and insulin resistance were calculated. The Zucker fatty rats fed 5% SCF-enriched diet showed less weight gain and food intake than those fed the standard diet. The group fed the fiber-enriched diet showed lower values of the total cholesterol/high-density lipoprotein cholesterol ratio and triglyceride levels than the standard group. FAD was also lower in the fiber group. Both SBP and DBP were decreased. In addition, SCF reduced plasma glucose and insulin, and as a consequence the insulin resistance was also decreased. Our data demonstrate that SCF resulted in an improvement of the studied risk factors associated with cardiometabolic disorders.
    Full-text · Article · Jun 2010 · Journal of medicinal food