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1.
Antioxidants (Basel) ; 12(4)2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37107352

RESUMEN

Obesity is a global health issue, in which modifications in gut microbiota composition have a key role. Different therapeutic strategies are being developed in combination with diet and exercise, including the use of plant extracts, such as those obtained from Morus alba L. leaves. Recent studies have revealed their anti-inflammatory and antioxidant properties. The aim of the present work was to evaluate whether the beneficial effects of M. alba L. leaf extract in high-fat diet-induced obesity in mice is correlated with its impact on gut microbiota. The extract reduced body weight gain and attenuated lipid accumulation, as well as increased glucose sensitivity. These effects were associated with an amelioration of the obesity-associated inflammatory status, most probably due to the described antioxidant properties of the extract. Moreover, M. alba L. leaf extract mitigated gut dysbiosis, which was evidenced by the restoration of the Firmicutes/Bacteroidota ratio and the decrease in plasma lipopolysaccharide (LPS) levels. Specifically, the extract administration reduced Alistipes and increased Faecalibaculum abundance, these effects being correlated with the beneficial effects exerted by the extract on the obesity-associated inflammation. In conclusion, anti-obesogenic effects of M. alba L. leaf extract may be mediated through the amelioration of gut dysbiosis.

2.
Sci Rep ; 12(1): 9431, 2022 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-35676396

RESUMEN

The excavations undertaken at the Campo de Hockey site in 2008 led to the identification of a major Neolithic necropolis in the former Island of San Fernando (Bay of Cádiz). This work presents the results of the latest studies, which indicate that the site stands as one of the oldest megalithic necropolises in the Iberian Peninsula. The main aim of this work is to present with precision the chronology of this necropolis through a Bayesian statistical model that confirms that the necropolis was in use from c. 4300 to 3800 cal BC. The presence of prestige grave goods in the earliest and most monumental graves suggest that the Megalithism phenomenon emerged in relation to maritime routes linked to the distribution of exotic products. We also aim to examine funerary practices in these early megalithic communities, and especially their way of life and the social reproduction system. As such, in addition to the chronological information and the Bayesian statistics, we provide the results of a comprehensive interdisciplinary study, including anthropological, archaeometric and genetic data.


Asunto(s)
Hockey , Antropología , Arqueología , Teorema de Bayes , Europa (Continente) , Historia Antigua
3.
Mol Nutr Food Res ; 64(13): e2000005, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32415899

RESUMEN

SCOPE: Obesity is characterized by a dysfunction in the adipose tissue and an inflammatory subclinical state leading to insulin resistance and increased risk of cardiovascular diseases. It is also associated with intestinal dysbiosis that contributes to inflammation development. Lippia citriodora (LCE) contains high levels of polyphenolpropanoids and has shown promising results in obesity. The aim of this study is to investigate a well-characterized extract of LCE in a model of metabolic syndrome in mice, focusing on its effects on metabolic tissues, endothelial dysfunction, and microbiome. METHODS: Mice are fed a high fat diet (HFD) for six weeks and treated daily with LCE (1, 10, and 25 mg kg-1 ). Glucose and lipid metabolism is investigated. The inflammatory state in the metabolic tissues and the intestinal microbiota composition are characterized, as well as the endothelium-dependent vasodilator response to acetylcholine. RESULTS: LCE reduces fat accumulation and improves plasma glycemic and lipid profiles, as well as the inflammatory process and vascular dysfunction. Moreover, LCE lessens intestinal dysbiosis, as it reduces the Firmicutes/Bacteroidetes ratio and increases Akkermansia abundance in comparison with untreated HFD mice. CONCLUSION: The antiobesity therapeutic properties of LCE are most probably mediated by the synergic effects of its bioactive compounds.


Asunto(s)
Microbioma Gastrointestinal/efectos de los fármacos , Lippia/química , Obesidad/dietoterapia , Extractos Vegetales/farmacología , Animales , Fármacos Antiobesidad/química , Fármacos Antiobesidad/farmacología , Peso Corporal/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Suplementos Dietéticos , Disbiosis/dietoterapia , Disbiosis/microbiología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Microbioma Gastrointestinal/fisiología , Prueba de Tolerancia a la Glucosa , Lípidos/sangre , Masculino , Síndrome Metabólico/dietoterapia , Síndrome Metabólico/microbiología , Ratones Endogámicos C57BL , Obesidad/etiología , Obesidad/microbiología , Extractos Vegetales/química
4.
Arch. argent. pediatr ; 118(1): 64-67, 2020-02-00.
Artículo en Inglés, Español | LILACS, BINACIS | ID: biblio-1095682

RESUMEN

En los últimos años, se ha observado un incremento significativo en el interés por la prescripción del cannabis medicinal. En el siguiente artículo, se informa acerca de la escasa base científica que avala la prescripción de estos compuestos en un listado amplio y diverso de patologías médicas. Se considera fundamental que cualquier sustancia que vaya a ser utilizada en humanos siga un protocolo de aprobación estricto y científico, que pueda desligarse de modas o de resultados individuales. Es necesario que, antes de la prescripción de una droga en personas, deba tenerse un panorama claro de cuáles son los usos del compuesto en cuestión, pero, sobre todo, de su seguridad, que es prácticamente desconocida en el cannabis medicinal.


In recent years, the interest in medical cannabis prescription has increased significantly. This article provides information about the little scientific basis supporting the prescription of these products for a wide and diverse range of medical conditions. It is critical for any substance to be used in human beings to follow a strict scientific approval protocol, detached from any trend or individual outcome. Before prescribing any drug to human beings, it is necessary to have a clear picture of its uses, especially its safety, which is practically unknown in the case of medical cannabis.


Asunto(s)
Humanos , Cannabidiol/efectos adversos , Cannabidiol/uso terapéutico , Marihuana Medicinal/efectos adversos , Marihuana Medicinal/uso terapéutico , Seguridad , Dronabinol/uso terapéutico , Cannabidiol/farmacología , Ensayos de Uso Compasivo , Legislación de Medicamentos
5.
Arch Argent Pediatr ; 118(1): 64-67, 2020 02.
Artículo en Inglés, Español | MEDLINE | ID: mdl-31984702

RESUMEN

In recent years, the interest in medical cannabis prescription has increased significantly. This article provides information about the little scientific basis supporting the prescription of these products for a wide and diverse range of medical conditions. It is critical for any substance to be used in human beings to follow a strict scientific approval protocol, detached from any trend or individual outcome. Before prescribing any drug to human beings, it is necessary to have a clear picture of its uses, especially its safety, which is practically unknown in the case of medical cannabis.


En los últimos años, se ha observado un incremento significativo en el interés por la prescripción del cannabis medicinal. En el siguiente artículo, se informa acerca de la escasa base científica que avala la prescripción de estos compuestos en un listado amplio y diverso de patologías médicas. Se considera fundamental que cualquier sustancia que vaya a ser utilizada en humanos siga un protocolo de aprobación estricto y científico, que pueda desligarse de modas o de resultados individuales. Es necesario que, antes de la prescripción de una droga en personas, deba tenerse un panorama claro de cuáles son los usos del compuesto en cuestión, pero, sobre todo, de su seguridad, que es prácticamente desconocida en el cannabis medicinal.


Asunto(s)
Aprobación de Drogas , Marihuana Medicinal/uso terapéutico , Argentina , Aprobación de Drogas/legislación & jurisprudencia , Humanos , Marihuana Medicinal/efectos adversos , Riesgo
6.
Mol Nutr Food Res ; 64(6): e1900616, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31953983

RESUMEN

SCOPE: The objective of this study is to determine the cardiovascular effects of the probiotics Bifidobacterium breve CECT7263 (BFM) and Lactobacillus fermentum CECT5716 (LC40), and the short chain fatty acids butyrate, and acetate in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: Ten five-week old Wistar Kyoto rats (WKY) and fifty aged-matched SHR are randomly distributed into six groups: control WKY, control SHR, treated SHR-LC40, treated SHR-BMF, treated SHR-butyrate, and treated SHR-acetate. Chronic treatments with LC40 or BFM increase butyrate-producing bacteria and prevent the blood pressure increase in SHR. Oral treatment with butyrate or acetate also prevents the increase in both blood pressure and Firmicutes/Bacteroidetes (F/B) ratio. All treatments restore the Th17/Treg balance in mesenteric lymph nodes, normalized endotoxemia, and prevent the impairment of endothelium-dependent relaxation to acetylcholine, as a result of reduced NADPH oxidase-driven reactive oxygen species production. These protective effects might be mediated by both the reduction in vascular lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) pathway and the increase in Treg infiltration in the vasculature. CONCLUSION: The probiotics LC40 and BFM prevent dysbiosis and the development of endothelial dysfunction and high blood pressure in genetic hypertension. These effects seem to be related to endotoxemia reduction and to increase Treg accumulation in the vasculature.


Asunto(s)
Bifidobacterium breve , Cardiomegalia/prevención & control , Disbiosis/prevención & control , Ácidos Grasos Volátiles/farmacología , Probióticos/farmacología , Acetatos/administración & dosificación , Acetatos/metabolismo , Acetatos/farmacología , Administración Oral , Animales , Antihipertensivos/administración & dosificación , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Suplementos Dietéticos , Disbiosis/microbiología , Ácidos Grasos Volátiles/análisis , Ácidos Grasos Volátiles/sangre , Microbioma Gastrointestinal , Hipertensión/dietoterapia , Masculino , Probióticos/administración & dosificación , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Linfocitos T
7.
Food Res Int ; 127: 108722, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31882094

RESUMEN

The metabolic syndrome has been associated with an alteration of intestinal microbiota, which can be considered as a target for the management of these patients. Phenolic extracts from Hibiscus sabdariffa have shown beneficial effects on obesity and its related complications. However, their effects on gut microbiota have not been investigated yet. This study evaluates the effects of a chemically characterized polyphenolic extract of H. sabdariffa (HSE) in an experimental model of diet-induced obesity (DIO) in mice. HSE was administered daily by oral gave for 42 days. HSE reduced weight increase in high fat diet (HFD)-fed mice, and improved glucose tolerance, insulin sensitivity and normalized LDL/HDL cholesterol ratio. It also enhanced the inflammatory state in the liver, reducing the expression of different adipokines and proinflammatory mediators, and reinforced gut integrity by increasing the expression of mucins and proteins involved in the maintenance of mucosal barrier. Moreover, HSE had a prebiotic effect, ameliorating the changes in the gut microbiota induced by the HFD. Thus, HSE improved the Firmicutes/Bacteroidetes ratio, which may contribute to the beneficial effects. Consequently, HSE could be considered for the development of a complementary treatment for the metabolic syndrome due to its beneficial properties.


Asunto(s)
Hibiscus/química , Obesidad/tratamiento farmacológico , Extractos Vegetales/farmacología , Prebióticos , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL
8.
Pharmacol Res ; 150: 104487, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31610229

RESUMEN

INTRODUCTION: Many studies have showed the beneficial effects of the olive (Olea europaea) leaf extract (OLE) in experimental models of metabolic syndrome, which have been ascribed to the presence of phenolic compounds, like oleuropeoside. This study evaluated the effects of a chemically characterized OLE in high fat diet (HFD)-induced obesity in mice, describing the underlying mechanisms involved in the beneficial effects, with special attention to vascular dysfunction and gut microbiota composition. METHODS: C57BL/6J mice were distributed in different groups: control, control-treated, obese and obese-treated with OLE (1, 10 and 25 mg/kg/day). Control mice received a standard diet, whereas obese mice were fed HFD. The treatment was followed for 5 weeks, and animal body weight periodically assessed. At the end of the treatment, metabolic plasma analysis (including lipid profile) as well as glucose and insulin levels were performed. The HFD-induced inflammatory status was studied in liver and fat, by determining the RNA expression of different inflammatory mediators by qPCR; also, different markers of intestinal epithelial barrier function were determined in colonic tissue by qPCR. Additionally, flow cytometry of immune cells from adipose tissue, endothelial dysfunction in aortic rings as well as gut microbiota composition were evaluated. Faecal microbiota transplantation (FMT) to antibiotic-treated mice fed with HFD was performed. RESULTS: OLE administration reduced body weight gain, basal glycaemia and insulin resistance, and showed improvement in plasma lipid profile when compared with HFD-fed mice. The extract significantly ameliorated the HFD-induced altered expression of key adipogenic genes, like PPARs, adiponectin and leptin receptor, in adipose tissue. Furthermore, the extract reduced the RNA expression of Tnf-α, Il-1ß, Il-6 in liver and adipose tissue, thus improving the tissue inflammatory status associated to obesity. The flow cytometry analysis in adipose tissue corroborated these observations. Additionally, the characterization of the colonic microbiota by sequencing showed that OLE administration was able to counteract the dysbiosis associated to obesity. The extract reversed the endothelial dysfunction observed in the aortic rings of obese mice. FMT from donors HFD-OLE to recipient mice fed an HFD prevented the development of obesity, glucose intolerance, insulin resistance and endothelial dysfunction. CONCLUSION: OLE exerts beneficial effects in HFD-induced obesity in mice, which was associated to an improvement in plasma and tissue metabolic profile, inflammatory status, gut microbiota composition and vascular dysfunction.


Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Disbiosis/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Obesidad/tratamiento farmacológico , Olea , Extractos Vegetales/uso terapéutico , Adipogénesis/efectos de los fármacos , Adipogénesis/genética , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Fármacos Antiobesidad/farmacología , Aorta Torácica/efectos de los fármacos , Aorta Torácica/fisiología , Citocinas/genética , Dieta Alta en Grasa , Disbiosis/metabolismo , Disbiosis/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Factores Inmunológicos/farmacología , Resistencia a la Insulina , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , NADPH Oxidasas/metabolismo , Obesidad/metabolismo , Obesidad/microbiología , Fitoterapia , Extractos Vegetales/farmacología , Hojas de la Planta
9.
EMBO Mol Med ; 11(1)2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30482867

RESUMEN

Coenzyme Q (CoQ) deficiency has been associated with primary defects in the CoQ biosynthetic pathway or to secondary events. In some cases, the exogenous CoQ supplementation has limited efficacy. In the Coq9R239X mouse model with fatal mitochondrial encephalopathy due to CoQ deficiency, we have tested the therapeutic potential of ß-resorcylic acid (ß-RA), a structural analog of the CoQ precursor 4-hydroxybenzoic acid and the anti-inflammatory salicylic acid. ß-RA noticeably rescued the phenotypic, morphological, and histopathological signs of the encephalopathy, leading to a significant increase in the survival. Those effects were due to the decrease of the levels of demethoxyubiquinone-9 (DMQ9) and the increase of mitochondrial bioenergetics in peripheral tissues. However, neither CoQ biosynthesis nor mitochondrial function changed in the brain after the therapy, suggesting that some endocrine interactions may induce the reduction of the astrogliosis, spongiosis, and the secondary down-regulation of astrocytes-related neuroinflammatory genes. Because the therapeutic outcomes of ß-RA administration were superior to those after CoQ10 supplementation, its use in the clinic should be considered in CoQ deficiencies.


Asunto(s)
Hidroxibenzoatos/administración & dosificación , Encefalomiopatías Mitocondriales/tratamiento farmacológico , Encefalomiopatías Mitocondriales/patología , Fármacos Neuroprotectores/administración & dosificación , Ubiquinona/análogos & derivados , Animales , Encéfalo/patología , Encéfalo/fisiopatología , Modelos Animales de Enfermedad , Metabolismo Energético , Histocitoquímica , Ratones , Ácido Salicílico/administración & dosificación , Análisis de Supervivencia , Resultado del Tratamiento , Ubiquinona/análisis , Ubiquinona/deficiencia , Ubiquinona/genética , Ubiquinona/metabolismo
10.
Food Res Int ; 96: 64-71, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28528109

RESUMEN

Obesity is associated with a low-grade inflammatory status that affects vascular function. Previous studies have reported the beneficial effects of Psidium guajava L. (guava) on diabetes. Here we evaluate the how guava leaf extract at the dose of 5 mg/kg, affects vascular dysfunction in obese mice fed a high-fat diet for 7 weeks. Extract intake did not alter weight over time, although it reduced glycemia and insulin resistance, improving the serum lipid profile in obese mice. Additionally, guava leaf extract reversed the endothelial dysfunction found in obese mice in terms of endothelium- and NO (nitric oxide)-dependent vasodilatation induced by acetylcholine in aortic rings. In conclusion, the beneficial effects of guava leaf extract in obese mice were associated with improved vascular functions altered by obesity, probably due to its phenolic content.


Asunto(s)
Glucemia/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Dieta Alta en Grasa , Endotelio Vascular/efectos de los fármacos , Hipoglucemiantes/farmacología , Obesidad/etiología , Extractos Vegetales/farmacología , Hojas de la Planta , Psidium , Vasodilatación/efectos de los fármacos , Animales , Biomarcadores/sangre , Glucemia/metabolismo , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/etiología , Diabetes Mellitus Experimental/fisiopatología , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiología , Hipoglucemiantes/aislamiento & purificación , Insulina/sangre , Resistencia a la Insulina , Lípidos/sangre , Masculino , Ratones Endogámicos C57BL , Óxido Nítrico/metabolismo , Obesidad/sangre , Obesidad/fisiopatología , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Psidium/química
11.
J Sci Food Agric ; 92(9): 1822-5, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22555950

RESUMEN

Flavonoids have been proposed to exert beneficial effects in the prevention of a large number of diseases, including cancer, cardiovascular disease, and neurodegenerative disorders. Paradoxically, despite the most representative flavonoid--quercetin--exerting biologically demonstrable systemic effects, it is not found in plasma after oral administration and its circulating metabolites show weak activity in vitro. The current available evidence indicates that quercetin is extensively metabolized into methylated and glucurono- and sulfo-conjugated metabolites, which are the plasma circulating forms; and glucurono-, but not sulfo-conjugates, can be hydrolyzed at the vascular level, yielding the parent aglycone which accumulates in tissues. Thus conjugation is a reversible process and, at least regarding the vasodilator and antihypertensive effects, the conjugation-deconjugation cycle appears to be an absolute requirement. Glucuronidated derivatives transport quercetin and its methylated form, and deliver to the tissues the free aglycone, which is the final effector.


Asunto(s)
Fase II de la Desintoxicación Metabólica , Fitoterapia , Extractos Vegetales/metabolismo , Quercetina/metabolismo , Antihipertensivos/metabolismo , Antineoplásicos Fitogénicos/metabolismo , Transporte Biológico , Vasos Sanguíneos/efectos de los fármacos , Vasos Sanguíneos/metabolismo , Humanos , Hidrólisis , Metilación , Fármacos Neuroprotectores/metabolismo , Extractos Vegetales/farmacología , Quercetina/farmacología , Vasodilatadores/metabolismo
12.
J Agric Food Chem ; 60(36): 8823-30, 2012 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-22440087

RESUMEN

Epidemiological studies indicate an inverse relationship between flavanol intake and the risk of cardiovascular disease. Potential mechanisms include their effects on endothelial function and hypertension. A number of studies have shown that flavanol-rich cocoa reduces blood pressure and endothelial dysfunction, whereas black tea may have opposite effects. These results highlight the importance of the different effects of the multitude of phytochemical constituents in these foods and the need for studying the individual flavanols. Epicatechin seems to be a major bioactive constituent of cocoa and other flavanol-rich foods and beverages. It has been shown to improve endothelial function in animals and humans. In salt-sensitive animal models of hypertension, epicatechin lowers blood pressure and the associated end-organ damage. Nitric oxide (NO) seems to play a key role in the protection of both hypertension and endothelial dysfunction.


Asunto(s)
Presión Sanguínea/efectos de los fármacos , Catequina/farmacología , Endotelio Vascular/efectos de los fármacos , Hipertensión/fisiopatología , Extractos Vegetales/farmacología , Animales , Endotelio Vascular/fisiopatología , Humanos , Hipertensión/tratamiento farmacológico , Vasodilatación/efectos de los fármacos
13.
ACS Appl Mater Interfaces ; 3(12): 4552-6, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22077378

RESUMEN

We present a sugar-templated polydimethylsiloxane (PDMS) sponge for the selective absorption of oil from water. The process for fabricating the PDMS sponge does not require any intricate synthesis processes or equipment and it is not environmentally hazardous, thus promoting potential in environmental applications. The proposed PDMS sponge can be elastically deformed into any shape, and it can be compressed repeatedly in air or liquids without collapsing. Therefore, absorbed oils and organic solvents can be readily removed and reused by simply squeezing the PDMS sponge, enabling excellent recyclability. Furthermore, through appropriately combining various sugar particles, the absorption capacity of the PDMS sponge is favorably optimized.


Asunto(s)
Dimetilpolisiloxanos/química , Restauración y Remediación Ambiental/instrumentación , Petróleo/análisis , Contaminantes Químicos del Agua/química , Absorción , Contaminación por Petróleo
14.
Br J Nutr ; 106(9): 1337-48, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21910946

RESUMEN

The present study analysed the effects of the flavanol (-)-epicatechin in rats after chronic inhibition of NO synthesis with NG-nitro-L-arginine methyl ester (L-NAME), at doses equivalent to those achieved in the studies involving human subjects. Wistar rats were randomly divided into four groups: (1) control-vehicle, (2) L-NAME, (3) L-NAME-epicatechin 2 (L-NAME-Epi 2) and (4) L-NAME-epicatechin 10 (L-NAME-Epi 10). Rats were daily given by oral administration for 4 weeks: vehicle, (-)-epicatechin 2 or 10 mg/kg. Animals in the L-NAME groups daily received L-NAME 75 mg/100 ml in drinking-water. The evolution in systolic blood pressure and heart rate, and morphological and plasma variables, proteinuria, vascular superoxide, reactivity and protein expression at the end of the experiment were analysed. Chronic (-)-epicatechin treatment did not modify the development of hypertension and only weakly affected the endothelial dysfunction induced by L-NAME but prevented the cardiac hypertrophy, the renal parenchyma and vascular lesions and proteinuria, and blunted the prostanoid-mediated enhanced endothelium-dependent vasoconstrictor responses and the cyclo-oxygenase-2 and endothelial NO synthase (eNOS) up-regulation. Furthermore, (-)-epicatechin also increased Akt and eNOS phosphorylation and prevented the L-NAME-induced increase in systemic (plasma malonyldialdehyde and urinary 8-iso-PGF2α) and vascular (dihydroethidium staining, NADPH oxidase activity and p22phox up-regulation) oxidative stress, proinflammatory status (intercellular adhesion molecule-1, IL-1ß and TNFα up-regulation) and extracellular-signal-regulated kinase 1/2 phosphorylation. The present study shows for the first time that chronic oral administration of (-)-epicatechin does not improve hypertension but reduced pro-atherogenic pathways such as oxidative stress and proinflammatory status of the vascular wall induced by blockade of NO production.


Asunto(s)
Catequina/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Inflamación/tratamiento farmacológico , Óxido Nítrico/deficiencia , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Enfermedades Vasculares/tratamiento farmacológico , Animales , Aterosclerosis/prevención & control , Presión Sanguínea/efectos de los fármacos , Catequina/administración & dosificación , Catequina/farmacología , Ciclooxigenasa 2/sangre , Endotelio Vascular/fisiopatología , Hipertensión , Hipertrofia , Mediadores de Inflamación/sangre , Riñón/efectos de los fármacos , Riñón/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Miocardio/patología , NG-Nitroarginina Metil Éster , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Fosforilación , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Prostaglandinas/metabolismo , Proteinuria/tratamiento farmacológico , Ratas , Ratas Wistar , Regulación hacia Arriba , Enfermedades Vasculares/metabolismo , Enfermedades Vasculares/patología , Enfermedades Vasculares/fisiopatología , Vasoconstricción/efectos de los fármacos
15.
Curr Opin Investig Drugs ; 11(9): 1039-47, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20730699

RESUMEN

The nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine-3',5'-monophosphate (cGMP) pathway plays an important role in cardiovascular regulation by producing vasodilation and inhibiting platelet aggregation and vascular smooth muscle proliferation. The NO/SGC/cGMP pathway is disrupted in patients with heart failure as a result of a decrease in NO bioavailability and an increase in NO-insensitive forms of sGC, resulting in insufficient vasodilation. Drugs that activate sGC in a NO-independent manner may provide considerable therapeutic advantages in treating these patients. Cinaciguat (BAY-58-2667), currently in development by Bayer AG, preferentially activates sGC in its oxidized or heme-free state, when the enzyme is insensitive to both NO and nitrovasodilators. Cinaciguat exhibits potent vasodilator and antiplatelet activity, a long-lasting antihypertensive effect and a hemodynamic profile similar to that of nitrates. In clinical trials in patients with acute decompensated heart failure, cinaciguat potently unloaded the heart, increased cardiac output and renal blood flow, and preserved renal function and sodium and water excretion without further neurohumoral activation. The pharmacokinetics of cinaciguat demonstrated dose-proportionality with low individual variability and a low incidence of adverse events. The phase I and II clinical trials performed with cinaciguat so far, however, are insufficient to provide convincing evidence on the efficacy and safety of the drug. Thus, caution should be exerted before extrapolating the present preliminary data to the clinical practice.


Asunto(s)
Benzoatos/uso terapéutico , Activadores de Enzimas/uso terapéutico , Guanilato Ciclasa/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Enfermedad Aguda , Animales , Benzoatos/metabolismo , Benzoatos/farmacocinética , Benzoatos/farmacología , Sistema Cardiovascular/efectos de los fármacos , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatología , Ensayos Clínicos como Asunto , Evaluación Preclínica de Medicamentos , Activadores de Enzimas/metabolismo , Activadores de Enzimas/farmacocinética , Activadores de Enzimas/farmacología , Insuficiencia Cardíaca/fisiopatología , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Vasodilatadores/metabolismo , Vasodilatadores/farmacocinética , Vasodilatadores/farmacología , Vasodilatadores/uso terapéutico
16.
Planta Med ; 74(7): 741-6, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18484521

RESUMEN

Quercetin, the most abundant flavonoid in the diet, reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (as the aglycone) is usually not present in plasma, but it is rapidly metabolised during absorption by methylation, glucuronidation and sulfation. Depending on the experimental conditions, quercetin can show anti-oxidant or pro-oxidant effects. We have analysed the pro-oxidant effects of quercetin and its methylated (3-methylquercetin or isorhamnetin), sulfated (quercetin 3'-sulfate), glucuronidated (quercetin 3-glucuronide) and methylated plus glucuronidated (isorhamnetin 3-glucuronide) metabolites. Auto-oxidation, O(2)(-) release and NO scavenging were analysed by means of absorption spectra, lucigenin chemiluminescence or superoxide dismutase inhibitable cytochrome C reduction and an amperometric electrode, respectively. The biological activity of NO was tested in rat aortic rings. Quercetin, isorhamnetin and quercetin 3'-sulfate auto-oxidized in aqueous buffer and generated superoxide radical. Quercetin but not the glucuronide scavenged NO. In contrast, the glucuronides were without effect. Quercetin, but not quercetin 3-glucuronide, inhibited the biological activity of NO. These data indicate that, in contrast to quercetin, its main circulating forms, i. e., the glucuronides, do not exert pro-oxidant effects.


Asunto(s)
Aorta/metabolismo , Glucuronidasa/metabolismo , Óxido Nítrico/metabolismo , Quercetina/metabolismo , Animales , Radicales Libres/metabolismo , Técnicas In Vitro , Masculino , Ratas , Ratas Wistar
17.
Menopause ; 14(5): 933-40, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17667142

RESUMEN

OBJECTIVE: The soy-derived phytoestrogen genistein improves endothelial function in postmenopausal women and ovariectomized (OVX) normotensive rats. We hypothesized that genistein would improve vascular reactivity involving changes in endothelial nitric oxide synthase (NOS) expression and its regulatory proteins (caveolin and calmodulin), angiotensin II receptor, and/or oxidative status in OVX spontaneously hypertensive rats (SHRs). DESIGN: After ovariectomy or sham operation, 23-week-old female SHRs received either 17beta-estradiol (2 mg/kg/wk SC), genistein (10 mg/kg/d by gavage), or placebo. RESULTS: In OVX rats, final body weight was increased and uterus weight was decreased, and these values were reduced and increased, respectively, by 17beta-estradiol but unaffected by genistein. Acetylcholine-induced endothelium-dependent vasorelaxation was significantly blunted in aortas from OVX placebo SHRs. The contractions induced by the NOS inhibitor L-NAME and angiotensin II in OVX placebo were lower and higher, respectively, than in sham rats. Estradiol and genistein restored these functional changes. Aortic endothelial NOS and calmodulin-1 expression were unchanged, whereas caveolin-1 and angiotensin II receptor expression was increased in OVX rats. Estradiol and genistein treatment did not modify endothelial NOS, but normalized caveolin-1 and angiotensin II receptor and increased calmodulin-1 expression. Vascular superoxide production was increased in OVX placebo and normalized by both estradiol and genistein. CONCLUSIONS: Genistein prevented all cardiovascular changes induced by estrogen depletion in SHRs to a similar extent as estradiol but had no uterotrophic effect. The present findings may help to explain the potential benefits of genistein as a therapeutic agent for preventing menopausal vascular complications, especially in hypertensive women.


Asunto(s)
Caveolina 1/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Genisteína/farmacología , Ovariectomía , Fitoestrógenos/farmacología , Receptor de Angiotensina Tipo 1/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Animales , Aorta/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Genisteína/administración & dosificación , Fitoestrógenos/administración & dosificación , Distribución Aleatoria , Ratas , Ratas Endogámicas SHR , Vasodilatadores/farmacología
18.
Planta Med ; 71(9): 829-34, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16206037

RESUMEN

In the present study, the effects of the bioflavonoid chrysin (5,7-dihydroxyflavone) were analysed on nitric oxide (NO) production from vascular endothelium. In aortic rings, incubation with chrysin or acetylcholine (both at 10 microM) increased L-NAME-sensitive endothelial NO release as measured using the fluorescent probe 4,5-diaminofluorescein diacetate (DAF-2 DA). Moreover, chrysin increased cGMP accumulation only in aortic rings with endothelium. However, at this concentration, chrysin had no effect either on basal or on NADPH-stimulated vascular superoxide production. Moreover, at this low concentration, chrysin, similar to acetylcholine, induced aortic relaxation, which was abolished by both endothelial deprivation and NO synthase inhibition. Endothelium-dependent relaxation induced by chrysin was unaltered by removal of extracellular calcium and incubation with the intracellular calcium chelator BAPTA, while the phosphatidylinositol (PI)-3 kinase inhibitor wortmannin suppressed the endothelial dependence. In conclusion, chrysin stimulated NO release from endothelial cells leading to vascular cGMP accumulation and subsequent endothelium dependent aortic relaxation. Chrysin-stimulated NO release is calcium independent and possibly mediated via PI3-kinase.


Asunto(s)
Endotelio Vascular/efectos de los fármacos , Óxido Nítrico/metabolismo , Fitoterapia , Extractos Vegetales/farmacología , Plantas Medicinales , Vasodilatadores/farmacología , Animales , Aorta Torácica , Relación Dosis-Respuesta a Droga , Endotelio Vascular/metabolismo , Flavonoides/administración & dosificación , Flavonoides/farmacología , Flavonoides/uso terapéutico , Masculino , Relajación Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Ratas , Ratas Wistar , Vasodilatadores/administración & dosificación , Vasodilatadores/uso terapéutico
19.
J Nutr ; 135(10): 2399-404, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16177203

RESUMEN

The aim of the present study was to analyze whether consumption of a fiber-supplemented diet containing 3.5% Plantago ovata husks prevented many of the abnormalities clustered in the metabolic syndrome, including obesity, dyslipidemia, hypertension and endothelial dysfunction. For this purpose, obese Zucker rats, a model of type 2 diabetes, and their lean littermates were studied. Rats consumed a standard control diet or that diet supplemented with 3.5% P. ovata husks for 25 wk. Body weights were measured weekly. Systolic blood pressure (SBP) was measured monthly. At the end of the treatment, plasma concentrations of triglycerides, total cholesterol, FFAs, glucose, insulin, adiponectin, and tumor necrosis factor alpha (TNF-alpha) were determined, and studies on vascular function were performed using aortic rings. Rats fed the P. ovata husk-supplemented diet had a significantly reduced body weight gain compared with those fed the standard diet. Decreased endothelium-dependent relaxation in response to acetylcholine (ACh) by aortic rings from obese Zucker rats was improved in those fed the fiber-supplemented diet. The greater SBP, higher plasma concentrations of triglycerides, total cholesterol, FFA, glucose, insulin, and TNF-alpha, and the hypoadinectinemia that occurred in obese Zucker rats that consumed the control diet were significantly improved in those fed the fiber-supplemented diet. We conclude that intake of a P. ovata husk-supplemented diet prevents endothelial dysfunction, hypertension, and obesity development, and ameliorates dyslipidemia and abnormal plasma concentrations of adiponectin and TNF-alpha in obese Zucker rats.


Asunto(s)
Adiponectina/sangre , Hipertensión/dietoterapia , Síndrome Metabólico/dietoterapia , Obesidad/dietoterapia , Plantago , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Presión Sanguínea , Ingestión de Alimentos , Endotelio Vascular/fisiología , Hipertensión/sangre , Resistencia a la Insulina , Lípidos/sangre , Masculino , Síndrome Metabólico/sangre , Obesidad/sangre , Tamaño de los Órganos , Ratas , Ratas Zucker , Aumento de Peso
20.
Planta Med ; 70(4): 334-41, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15095149

RESUMEN

This study analysed and compared the effects of chronic oral treatment with quercetin or verapamil on systolic blood pressure and vascular function in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Quercetin and verapamil inhibited the development of DOCA-salt-induced hypertension in a similar manner. DOCA-salt-hypertensive rats showed potassium depletion and oxidative stress, prevented only by concomitant quercetin administration. Quercetin and verapamil treatments reduced the endothelium-independent hyper-reactivity to KCl observed in the aorta of DOCA-salt-hypertensive rats, but only quercetin increased the contractile responses to angiotensin II, improved endothelial dysfunction and restored basal aortic Cu/Zn SOD expression, altered in DOCA-salt-treated rats. In conclusion, quercetin and verapamil show similar antihypertensive effects in mineralocorticoid hypertension, but quercetin was superior to verapamil in improving endothelial-dependent aortic dilatation, suggesting a better vascular protection in this volume expansion hypertension model.


Asunto(s)
Antihipertensivos/farmacología , Hipertensión/prevención & control , Fitoterapia , Plantas Medicinales , Quercetina/farmacología , Animales , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Aorta/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Desoxicorticosterona , Modelos Animales de Enfermedad , Hipertensión/inducido químicamente , Masculino , Contracción Muscular/efectos de los fármacos , Cloruro de Potasio , Quercetina/administración & dosificación , Quercetina/uso terapéutico , Ratas , Ratas Wistar , Cloruro de Sodio , Verapamilo/farmacología
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