RESUMEN
Obesity is recognized as an independent risk factor for cardiovascular diseases and is an important contributor to cardiac mortality. Açaí seed extract (ASE), rich in proanthocyanidins, has been shown to have potential anti-obesity effects. This study aimed to investigate the therapeutic effect of ASE in cardiovascular remodeling associated with obesity and compare it with that of rosuvastatin. Male C57BL/6 mice were fed a high-fat diet or a standard diet for 12 weeks. The ASE (300 mg/kg/day) and rosuvastatin (20 mg/kg/day) treatments started in the 8th week until the 12th week, totaling 4 weeks of treatment. Our data showed that treatment with ASE and rosuvastatin reduced body weight, ameliorated lipid profile, and improved cardiovascular remodeling. Treatment with ASE but not rosuvastatin reduced hyperglycemia and oxidative stress by reducing immunostaining of 8-isoprostane and increasing SOD-1 and GPx expression in HFD mice. ASE and rosuvastatin reduced NOX4 expression, increased SIRT-1 and Nrf2 expression and catalase and GPx activities, and improved vascular and cardiac remodeling in HFD mice. The therapeutic effect of ASE was similar to that of rosuvastatin in reducing dyslipidemia and cardiovascular remodeling but was superior in reducing oxidative damage and hyperglycemia, suggesting that ASE was a promising natural product for the treatment of cardiovascular alterations associated with obesity.
Asunto(s)
Antioxidantes/uso terapéutico , Cardiomegalia/tratamiento farmacológico , Obesidad/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Remodelación Ventricular/efectos de los fármacos , Animales , Cardiomegalia/etiología , Dieta Alta en Grasa , Euterpe/química , Masculino , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/complicaciones , Proantocianidinas/uso terapéutico , Semillas/químicaRESUMEN
ABSTRACT: This study aimed to determine if açai seed extract (ASE) could reverse pre-existing cardiovascular and renal injury in an experimental model of renovascular hypertension (2 kidney, 1 clip, 2K1C). Young male rats (Wistar) were used to obtain 2K1C and sham groups. Animals received the vehicle, ASE (200 mg/kg/d), or enalapril (30 mg/kg/d) in drinking water from the third to sixth week after surgery. We evaluated systolic blood pressure by tail plethysmography, vascular reactivity in the rat isolated mesenteric arterial bed (MAB), serum and urinary parameters, plasma inflammatory cytokines by ELISA, MAB expression of endothelial nitric oxide synthase and its active form peNOS by Western blot, plasma and MAB oxidative damage and antioxidant activity by spectrophotometry, and vascular and cardiac structural changes by histological analysis. ASE and enalapril reduced the systolic blood pressure, restored the endothelial and renal functions, and decreased the inflammatory cytokines and the oxidative stress in 2K1C rats. Furthermore, both treatments reduced vascular and cardiac remodeling. ASE substantially reduced cardiovascular remodeling and recovered endothelial dysfunction in 2K1C rats probably through its antihypertensive, antioxidant, and anti-inflammatory actions, supplying a natural resource for the treatment of renovascular hypertension.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Enalapril/farmacología , Euterpe , Hipertensión Renovascular/tratamiento farmacológico , Extractos Vegetales/farmacología , Remodelación Vascular/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antihipertensivos/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Biomarcadores/sangre , Biomarcadores/orina , Modelos Animales de Enfermedad , Euterpe/química , Hipertensión Renovascular/metabolismo , Hipertensión Renovascular/fisiopatología , Mediadores de Inflamación/sangre , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Ratas WistarRESUMEN
Intrauterine hypoxia-ischemia (HI) provides a strong stimulus for a developmental origin of both the central nervous system and cardiovascular diseases. This study aimed to investigate vascular functional and structural changes, oxidative stress damage, and behavioral alterations in adult male offspring submitted to HI during pregnancy. The pregnant Wistar rats had a uterine artery clamped for 45 min on the 18th gestational day, submitting the offspring to hypoxic-ischemic conditions. The Sham group passed to the same surgical procedure as the HI rats, without occlusion of the maternal uterine artery, and the controls consisted of non-manipulated healthy animals. After weaning, the male pups were divided into three groups: control, sham, and HI, according to the maternal procedure. At postnatal day 90 (P90), the adult male offspring performed the open field and forced swim tests. In P119, the rats had their blood pressure checked and were euthanized. Prenatal HI induced a depressive behavior in adult male offspring associated with a reduced vasodilator response to acetylcholine in perfused mesenteric arterial bed, and reduced superoxide dismutase and glutathione peroxidase activities in the aorta compared to control and sham groups. Prenatal HI also increased the vasoconstrictor response to norepinephrine, the media thickness, collagen deposition, and the oxidative damage in the aorta from adult male offspring compared to control and sham groups. Our results suggest an association among prenatal HI and adult vascular structural and functional changes, oxidative stress damage, and depressive behavior.
Asunto(s)
Estrés Oxidativo , Efectos Tardíos de la Exposición Prenatal , Animales , Antioxidantes/farmacología , Femenino , Hipoxia/complicaciones , Masculino , Embarazo , Ratas , Ratas Wistar , Vasoconstrictores/farmacologíaRESUMEN
OBJECTIVES: Obesity is considered a risk factor for the development of non-alcoholic fatty liver disease (NAFLD). The hydroalcoholic extract obtained from the açai seed (ASE), rich in proanthocyanidins, has been shown a potential body weight regulator with antioxidant properties. This study aimed to investigate the therapeutic effect of ASE in obesity-associated NAFLD and compare it with Rosuvastatin. METHODS: Male C57BL/6 mice received a high-fat diet or standard diet for 12 weeks. The treatments with ASE (300 mg/kg per day) or rosuvastatin (20 mg/kg per day) began in the eighth week until the 12th week. KEY FINDINGS: Our data show that the treatments with ASE and rosuvastatin reduced body weight and hyperglycaemia, improved lipid profile and attenuated hepatic steatosis in HFD mice. ASE and Rosuvastatin reduced HMGCoA-Reductase and SREBP-1C and increased ABGC8 and pAMPK expressions in the liver. Additionally, ASE, but not Rosuvastatin, reduced NPC1L1 and increased ABCG5 and PPAR-α expressions. ASE and rosuvastatin increased SIRT-1 expression and antioxidant defence, although only ASE was able to decrease the oxidative damage in hepatic tissue. CONCLUSIONS: The therapeutic effect of ASE was similar to that of rosuvastatin in reducing dyslipidemia and hepatic steatosis but was better in reducing oxidative damage and hyperglycaemia.
Asunto(s)
Euterpe , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hipolipemiantes/farmacología , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Obesidad/tratamiento farmacológico , Extractos Vegetales/farmacología , Rosuvastatina Cálcica/farmacología , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Dislipidemias/metabolismo , Dislipidemias/prevención & control , Euterpe/química , Hiperglucemia/metabolismo , Hiperglucemia/prevención & control , Hipolipemiantes/aislamiento & purificación , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Obesidad/etiología , Obesidad/metabolismo , Obesidad/patología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , SemillasRESUMEN
The purpose of this study was to examine whether the supplementation with an açai (Euterpe oleracea Mart.) seed extract (ASE) would affect the aerobic exercise performance in rats and correlate with the vascular function, muscle oxidative stress and mitochondrial biogenesis. Male Wistar rats were divided into five groups: Sedentary, Sedentary with chronic supplementation of ASE, Training, Training with chronic (200 mg/Kg/day intragastric gavage for 5 weeks) or acute (30 min before the maximal treadmill stress test (MST) supplementation with ASE. The exercise training was performed on a treadmill (30 min/day; 5 days/week) for 4 weeks. The chronic supplementation with ASE increased the exercise time (58%) and the running distance (129%) in relation to the MST, while the Training group increased 40% and 78% and the Training with acute ASE group increased 30% and 63%, respectively. The training-induced increase of ACh vasodilation was not changed by ASE, but the norepinephrine-induced vasoconstriction was reduced by chronic and acute supplementation with ASE. The increased levels of malondialdehyde in soleus muscle homogenates from the Training group was reduced only by chronic supplementation with ASE. The muscle antioxidant defense, NO2 levels, and expression of the mitochondrial biogenesis-related proteins (PGC1α, SIRT-1, p-AMPK/AMPK, Nrf-2) were not different between Training and Sedentary groups, but all these parameters were increased in the Training with Chronic ASE compared with the Sedentary groups. In conclusion, chronic supplementation with ASE improves aerobic physical performance by increasing the vascular function, reducing the oxidative stress, and up-regulating the mitochondrial biogenesis key proteins.
Asunto(s)
Euterpe , Animales , Antioxidantes , Masculino , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , SemillasRESUMEN
The role of the renin-angiotensin system (RAS), oxidative stress, and inflammation on the development of obesity and its comorbidities has been extensively addressed. Euterpe oleracea Mart. (açaí) seed extract (ASE), with antioxidant and anti-inflammatory properties and capable to modulate plasma renin levels, has been evidenced as a potential regulator of body mass. We hypothesized that the supplementation with ASE might exert beneficial effects on obesity-related white adipose tissue changes and metabolic disorders by interfering with the local adipose tissue overexpression of RAS, inflammation, and oxidative stress in C57BL/6 mice fed a high-fat (HF) diet. The animals were fed a standard diet (10% fat, control), 60% fat (HF), HFâ¯+â¯ASE (300â¯mg/kg per day) and HFâ¯+â¯ENA (enalapril, 30â¯mg/kg per day) for 12â¯weeks. ASE and ENA prevented weight gain and adiposity, adipocyte hypertrophy, dyslipidemia, and insulin resistance. In adipose tissue, ASE increased the insulin receptor expression and reduced renin and AT1 receptor expression, which was associated with decreased plasma levels of renin and angiotensin II. Differently, ENA increased the expression of angiotensin-conversing enzyme 2, AT2, B2, and Mas receptors in adipose tissue. Also, ASE but not ENA decreased malondialdehyde and 8-isoprostane levels in adipose tissue. Finally, ASE and ENA reduced the adipose tissue inflammatory markers tumor necrosis factor alpha and interleukin 6. These results demonstrate that ASE prevented the adipocyte hypertrophy, obesity, hyperlipidemia, hyperglycemia, and insulin resistance in HF diet-fed mice. The downregulation of RAS in adipose tissue, reducing oxidative stress and inflammation, may contribute to the prevention of obesity-related disorders.
Asunto(s)
Tejido Adiposo Blanco/metabolismo , Dieta Alta en Grasa , Euterpe , Estrés Oxidativo , Extractos Vegetales/farmacología , Sistema Renina-Angiotensina/fisiología , Adipocitos/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Glucemia/análisis , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Enalapril/farmacología , Ingestión de Energía/efectos de los fármacos , Inflamación , Insulina/sangre , Lípidos/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Sistema Renina-Angiotensina/efectos de los fármacos , SemillasRESUMEN
Many studies suggest a protective role of phenolic compounds in mood disorders. We aimed to assess the effect of Euterpe oleracea (açaí) seed extract (ASE) on anxiety induced by periodic maternal separation (PMS) in adult male rats. Animals were divided into 6 groups: control, ASE, fluoxetine (FLU), PMS, PMS+ASE, and PMS+FLU. For PMS, pups were separated daily from the dam for 3 h between postnatal day (PN) 2 and PN21. ASE (200 mg·kg-1·day-1) and FLU (10 mg·kg-1·day-1) were administered by gavage for 34 days after stress induction, starting at PN76. At PN106 and PN108, the rats were submitted to open field (OF) and forced swim tests, respectively. At PN110, the rats were sacrificed by decapitation. ASE increased time spent in the center area in the OF test, glucocorticoid receptors in the hypothalamus, tropomyosin receptor kinase B (TRKB) levels in the hippocampus, and nitrite levels and antioxidant activity in the brain stem (PMS+ASE group compared with PMS group). ASE also reduced plasma corticotropin-releasing hormone levels, adrenal norepinephrine levels, and oxidative damage in the brain stem in adult male offspring submitted to PMS. In conclusion, ASE treatment has an anti-anxiety effect in rats submitted to PMS by reducing hypothalamic-pituitary-adrenal axis reactivity and increasing the nitric oxide (NO)-brain-derived neurotrophic factor (BDNF)-TRKB pathway and antioxidant defense in the central nervous system. Novelty ASE has anti-anxiety and antioxidant effects in early-life stress. ASE reduces hypothalamic-pituitary-adrenal axis reactivity. The anxiolytic effect of ASE may involve activation of the NO-BDNF-TRKB pathway in the central nervous system.
Asunto(s)
Ansiolíticos/farmacología , Antioxidantes/farmacología , Privación Materna , Extractos Vegetales/farmacología , Animales , Factor Neurotrófico Derivado del Encéfalo , Euterpe/química , Sistema Hipotálamo-Hipofisario , Masculino , Óxido Nítrico , Estrés Oxidativo , Sistema Hipófiso-Suprarrenal , Ratas , Ratas Wistar , Receptor trkB , Semillas/química , Estrés PsicológicoRESUMEN
This study investigated the protective effect of a Vitis vinifera L. grape skin extract (ACH09) on blood pressure, lipid profile, and oxidative status in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP), total cholesterol, triglyceride, and glucose levels, as well as oxidative damage and antioxidant activity in the plasma and kidney, were evaluated in four experimental groups: control Wistar rats (W-C) and SHR-C that received water, and Wistar rats and SHR treated with ACH09 (200 mg/kg/d) in drinking water for 12 weeks (W-ACH09 and SHR-ACH09, respectively). SBP increased in the SHR group compared with the W groups and the treatment with ACH09 prevented the development of hypertension. Plasma triglyceride and total cholesterol levels increased in SHR compared with W-C rats; these changes prevented by treatment with ACH09. Glucose levels did not differ between the groups. The SHR group had increased oxidative damage in plasma, as expressed by 2-thiobarbituric acid reactive substances (TBARS) levels, and this prevented by ACH09. Levels of TBARS in the kidneys were lower in the SHR-ACH09 group than in the SHR-C group. Further, ACH09 increased the superoxide dismutase activity in both the plasma and kidneys of both SHR and Wistar rats. These results suggest that ACH09 is protective against disruption of blood pressures, oxidant status, and lipid profile in SHR, and provide important evidence on the benefits of ACH09 on hypertension and associated cardiovascular complications.
RESUMEN
Objective: To investigate whether Euterpe oleracea Mart. (açaí) seed extract (ASE) prevents maternal cardiovascular changes and intrauterine growth restriction (IUGR) in experimental preeclampsia (PE).Methods: ASE administration (200 mg/kg/day) during mid to late pregnancy in a rat model of L-NAME-induced PE.Results: ASE impaired the maternal hypertension and microalbuminuria as well as the lower fetal and placental weight in experimental PE. ASE also prevented the maternal vascular dysfunction and lipoperoxidation in this model.Conclusion: ASE protected against maternal cardiovascular changes and IUGR in the L-NAME-induced PE. The protective effect of ASE may be partly explained by its antioxidant property.
Asunto(s)
Antioxidantes/uso terapéutico , Euterpe , Retardo del Crecimiento Fetal/prevención & control , Hipertensión Inducida en el Embarazo/prevención & control , Extractos Vegetales/uso terapéutico , Preeclampsia/fisiopatología , Animales , Antioxidantes/farmacología , Femenino , Retardo del Crecimiento Fetal/fisiopatología , Hipertensión Inducida en el Embarazo/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Embarazo , Ratas , Ratas WistarRESUMEN
A growing body of evidence suggests a protective role of polyphenols and exercise training on the disorders of type 2 diabetes mellitus (T2DM). We aimed to assess the effect of the açaí seed extract (ASE) associated with exercise training on diabetic complications induced by high-fat (HF) diet plus streptozotocin (STZ) in rats. Type 2 diabetes was induced by feeding rats with HF diet (55% fat) for 5 weeks and a single dose of STZ (35 mg/kg i.p.). Control (C) and Diabetic (D) animals were subdivided into four groups each: Sedentary, Training, ASE Sedentary, and ASE Training. ASE (200 mg/kg/day) was administered by gavage and the exercise training was performed on a treadmill (30min/day; 5 days/week) for 4 weeks after the diabetes induction. In type 2 diabetic rats, the treatment with ASE reduced blood glucose, insulin resistance, leptin and IL-6 levels, lipid profile, and vascular dysfunction. ASE increased the expression of insulin signaling proteins in skeletal muscle and adipose tissue and plasma GLP-1 levels. ASE associated with exercise training potentiated the reduction of glycemia by decreasing TNF-α levels, increasing pAKT and adiponectin expressions in adipose tissue, and IR and pAMPK expressions in skeletal muscle of type 2 diabetic rats. In conclusion, ASE treatment has an antidiabetic effect in type 2 diabetic rats by activating the insulin-signaling pathway in muscle and adipose tissue, increasing GLP-1 levels, and an anti-inflammatory action. Exercise training potentiates the glucose-lowering effect of ASE by activating adiponectin-AMPK pathway and increasing IR expression.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Euterpe , Hipoglucemiantes/uso terapéutico , Condicionamiento Físico Animal , Fitoterapia , Extractos Vegetales/uso terapéutico , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Glucemia/análisis , Terapia Combinada , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/terapia , Dieta Alta en Grasa , Evaluación Preclínica de Medicamentos , Péptido 1 Similar al Glucagón/sangre , Hemoglobina Glucada/análisis , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , Insulina/sangre , Resistencia a la Insulina , Interleucina-6/sangre , Leptina/sangre , Lípidos/sangre , Masculino , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Extractos Vegetales/farmacología , Distribución Aleatoria , Ratas , Ratas Wistar , Semillas/químicaRESUMEN
PURPOSE: Euterpe oleracea Mart. (açaí) seed extract (ASE), through its anti-hypertensive, antioxidant and anti-inflammatory properties, may be useful to treat or prevent human diseases. Several evidences suggest that oxidative stress and inflammation contribute to the pathogenesis of diabetic nephropathy; therefore, we tested the hypothesis that ASE (200 mg/kg-1day-1) prevents diabetes and hypertension-related oxidative stress and inflammation, attenuating renal injury. METHODS: Male rats with streptozotocin (STZ)-induced diabetes (D), and spontaneously hypertensive rats with STZ-induced diabetes (DH) were treated daily with tap water or ASE (D + ASE and DH + ASE, respectively) for 45 days. The control (C) and hypertensive (H) animals received water. RESULTS: The elevated serum levels of urea and creatinine in D and DH, and increased albumin excretion in HD were reduced by ASE. Total glomeruli number in D and DH, were increased by ASE that also reduced renal fibrosis in both groups by decreasing collagen IV and TGF-ß1 expression. ASE improved biomarkers of renal filtration barrier (podocin and nephrin) in D and DH groups and prevented the increased expression of caspase-3, IL-6, TNF-α and MCP-1 in both groups. ASE reduced oxidative damage markers (TBARS, carbonyl levels and 8-isoprostane) in D and DH associated with a decrease in Nox 4 and p47 subunit expression and increase in antioxidant enzyme activity in both groups (SOD, catalase and GPx). CONCLUSION: ASE substantially reduced renal injury and prevented renal dysfunction by reducing inflammation, oxidative stress and improving the renal filtration barrier, providing a nutritional resource for prevention of diabetic and hypertensive-related nephropathy.
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Antioxidantes/uso terapéutico , Nefropatías Diabéticas/prevención & control , Suplementos Dietéticos , Euterpe/química , Extractos Vegetales/uso terapéutico , Insuficiencia Renal/prevención & control , Semillas/química , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Antihipertensivos/uso terapéutico , Apoptosis , Biomarcadores/sangre , Biomarcadores/metabolismo , Biomarcadores/orina , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/dietoterapia , Diabetes Mellitus Experimental/inmunología , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Fibrosis , Barrera de Filtración Glomerular/inmunología , Barrera de Filtración Glomerular/metabolismo , Barrera de Filtración Glomerular/patología , Barrera de Filtración Glomerular/fisiopatología , Hipertensión/complicaciones , Hipertensión/dietoterapia , Hipertensión/inmunología , Hipertensión/fisiopatología , Mediadores de Inflamación/sangre , Mediadores de Inflamación/metabolismo , Riñón/inmunología , Riñón/metabolismo , Riñón/patología , Riñón/fisiopatología , Estrés Oxidativo , Ratas Endogámicas SHR , Insuficiencia Renal/complicaciones , Insuficiencia Renal/etiología , Insuficiencia Renal/metabolismoRESUMEN
Type 2 diabetes mellitus contributes to an increased risk of metabolic and morphological changes in key organs, such as the liver. We aimed to assess the effect of the açaí seed extract (ASE) associated with exercise training on hepatic steatosis induced by high-fat (HF) diet plus streptozotocin (STZ) in rats. Type 2 diabetes was induced by feeding rats with HF diet (55% fat) for 5 weeks, followed by a single low dose of STZ (35 mg/kg i.p.). Control and diabetic groups were subdivided into four groups that were fed with standard chow diet for 4 weeks. Control (C) group was subdivided into Sedentary C, Training C, ASE Sedentary C and ASE Training C. Diabetic (D) group was subdivided into Sedentary D, Training D, ASE Sedentary D and ASE Training D. ASE (200 mg/kg/day) was administered by intragastric gavage, and the exercise training was performed on a treadmill (30 min/day; 5 days/week). Treatment with ASE associated with exercise training reduced the blood glucose (70.2%), total cholesterol (81.2%), aspartate aminotransferase (51.7%) and hepatic triglyceride levels (66.8%) and steatosis (72%) in ASE Training D group compared with the Sedentary D group. ASE associated with exercise training reduced the hepatic lipogenic proteins' expression (77.3%) and increased the antioxidant defense (63.1%), pAMPK expression (70.2%), cholesterol transporters (71.1%) and the pLKB1/LKB1 ratio (57.1%) in type 2 diabetic rats. In conclusion, ASE treatment associated with exercise training protects against hepatic steatosis in diabetic rats by reducing hepatic lipogenesis and increasing antioxidant defense and cholesterol excretion.
Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Euterpe/química , Enfermedad del Hígado Graso no Alcohólico/dietoterapia , Condicionamiento Físico Animal , Extractos Vegetales/farmacología , Animales , Antioxidantes/metabolismo , Diabetes Mellitus Experimental/complicaciones , Enzimas/metabolismo , Glucógeno/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Enfermedad del Hígado Graso no Alcohólico/etiología , Carbonilación Proteica , Proteínas/metabolismo , Ratas Wistar , Semillas/químicaRESUMEN
We hypothesized that a polyphenol-rich extract from Vitis vinifera L. grape skin (GSE) may exert beneficial effects on obesity and related metabolic disorders induced by a high-fat diet (HFD). C57/BL6 mice were fed a standard diet (10% fat, control, and GSE groups) or an HFD (60% fat, high fat (HF), and HF + GSE) with or without GSE (200 mg/kg/day) for 12 weeks. GSE prevented weight gain; dyslipidemia; insulin resistance; the alterations in plasma levels of leptin, adiponectin, and resistin; and the deregulation of leptin and adiponectin expression in adipose tissue. These beneficial effects of GSE may be related to a positive modulation of insulin signaling proteins (IR, pIRS, PI3K, pAKT), pAMPK/AMPK ratio, and GLUT4 expression in muscle and adipose tissue. In addition, GSE prevented the oxidative damage, evidenced by the restoration of antioxidant activity and decrease of malondialdehyde and carbonyl levels in muscle and adipose tissue. Finally, GSE showed an anti-inflammatory action, evidenced by the reduced plasma and adipose tissue inflammatory markers (TNF-α, IL-6). Our results suggest that GSE prevented the obesity and related metabolic disorders in HF-fed mice by regulating insulin sensitivity and GLUT4 expression as well as by preventing the oxidative stress and inflammation in skeletal muscle and adipose tissue. Copyright © 2017 John Wiley & Sons, Ltd.
Asunto(s)
Tejido Adiposo/efectos de los fármacos , Antocianinas/farmacología , Músculo Esquelético/efectos de los fármacos , Obesidad/tratamiento farmacológico , Extractos Vegetales/farmacología , Vitis/química , Adiponectina/sangre , Tejido Adiposo/metabolismo , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Peso Corporal , Dieta Alta en Grasa , Frutas/química , Transportador de Glucosa de Tipo 4/metabolismo , Inflamación/tratamiento farmacológico , Insulina/sangre , Resistencia a la Insulina , Interleucina-6/metabolismo , Leptina/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Polifenoles/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Nonalcoholic fatty liver disease is one of the most common complications of obesity. The Vitis vinifera L. grape skin extract (ACH09) is an important source of polyphenols, which are related to its antioxidant and antihyperglycemic activities. We hypothesized that ACH09 could also exert beneficial effects on metabolic disorders associated with obesity and evaluated ACH09's influence on high-fat (HF) diet-induced hepatic steatosis and insulin resistance in C57BL/6 mice. The animals were fed a standard diet (10% fat, control) or an HF diet (60% fat, HF) with or without ACH09 (200mg/[kg d]) for 12weeks. Our results showed that ACH09 reduced HF diet-induced body weight gain, prevented hepatic lipid accumulation and steatosis, and improved hyperglycemia and insulin resistance. The underlying mechanisms of these beneficial effects of ACH09 may involve the activation of hepatic insulin-signaling pathway because the expression of phosphorylated insulin receptor substrate-1, phosphatidylinositol 3-kinase, phosphorylated Akt serine/threonine kinase 1, and glucose transporter 2 was increased by ACH09 and correlated with improvement of hyperglycemia, hyperinsulinemia, and insulin resistance. ACH09 reduced the expression of the lipogenic factor sterol regulatory-element binding protein-1c in the liver and upregulated the lipolytic pathway (phosphorylated liver kinase B1/phosphorylated adenosine-monophosphate-activated protein kinase), which was associated with normal hepatic levels of triglyceride and cholesterol and prevention of steatosis. ACH09 prevented the hepatic oxidative damage in HF diet-fed mice probably by restoration of antioxidant activity. In conclusion, ACH09 protected mice from HF diet-induced obesity, insulin resistance, and hepatic steatosis. The regulation of hepatic insulin signaling pathway, lipogenesis, and oxidative stress may contribute to ACH09's protective effect.
Asunto(s)
Dieta Alta en Grasa/efectos adversos , Hígado Graso/prevención & control , Resistencia a la Insulina , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Vitis/química , Animales , Antioxidantes/farmacología , Colesterol/sangre , Quinasas Ciclina-Dependientes/genética , Quinasas Ciclina-Dependientes/metabolismo , Hígado Graso/tratamiento farmacológico , Transportador de Glucosa de Tipo 2/genética , Transportador de Glucosa de Tipo 2/metabolismo , Insulina/metabolismo , Proteínas Sustrato del Receptor de Insulina/genética , Proteínas Sustrato del Receptor de Insulina/metabolismo , Lipogénesis/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Polifenoles/farmacología , Triglicéridos/sangre , Quinasa Activadora de Quinasas Ciclina-DependientesRESUMEN
Previously, we have demonstrated that the seeds of Euterpe oleracia Mart. (açaí) are rich in polyphenols with antihypertensive and antioxidant properties. This study evaluated the renal protective effects of the hydroalcoholic extract obtained from the seeds of açaí (ASE) fruits in two-kidney, one-clip (2K1C) renovascular hypertension. Young male Wistar rats were used to obtain 2K1C and sham groups. Animals received ASE (200 mg/(kg·day) in drinking water) or vehicle for 40 days. We evaluated serum and urinary parameters, renal structural changes, and oxidative status. The increase in systolic blood pressure of the 2K1C group was accompanied by a decrease in left kidney volume and number of glomeruli, as well as an increase in glomerular volume and collagen deposition. ASE prevented the alterations of these parameters, except the reduced kidney volume. Serum levels of urea and creatinine and urinary protein excretion were increased in the 2K1C group and treatment with ASE improved all these functional parameters. The increased oxidative damage in the 2K1C group, assessed by lipid and protein oxidation, was prevented by ASE. The nitrite content and both expression and activity of antioxidant enzymes (superoxide dismutase-1, catalase, and glutathione peroxidase) were lower in the 2K1C group and restored by ASE. ASE substantially reduced renal injury and prevented renal dysfunction in 2K1C rats probably through its antihypertensive and antioxidant effects, providing a natural resource for treatment and prevention of renovascular hypertension-related abnormalities.
Asunto(s)
Antihipertensivos/administración & dosificación , Euterpe/química , Hipertensión Renovascular/tratamiento farmacológico , Riñón/irrigación sanguínea , Extractos Vegetales/administración & dosificación , Animales , Presión Sanguínea/efectos de los fármacos , Catalasa/metabolismo , Humanos , Hipertensión Renovascular/metabolismo , Hipertensión Renovascular/fisiopatología , Riñón/lesiones , Riñón/metabolismo , Riñón/fisiopatología , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Semillas/química , Superóxido Dismutasa/metabolismoRESUMEN
The consumption of polyphenol-rich foods is associated with a decreased risk of mortality from cardiovascular diseases. Previously, we have demonstrated that the stone of Euterpe oleracea Mart. (açaí) from the Amazon region exerts vasodilator and antioxidant actions. This study examined the effect of açaí stone extract (ASE) on the vascular functional and structural changes and oxidative stress associated with the two-kidney, one-clip (2K-1C) renovascular hypertension. 2K-1C and sham-operated rats were treated with ASE 200 mg/kg/day (or vehicle) for 40 days. Blood pressure was measured by tail plethysmography, and the vascular reactivity was evaluated in the rat isolated mesenteric arterial bed. Mesenteric protein expression of endothelial nitric oxide synthase (eNOS), superoxide dismutase 1 and 2 (SOD1 and SOD2), metalloproteinase 2 (MMP-2), and tissue inhibitor of MMPs (TIMP)-1 was assessed by Western blot; oxidative damage and antioxidant activity by spectrophotometry; MMP-2 levels by gelatin zymography; and structural changes by histological analysis. ASE prevented 2K-1C hypertension and the reduction of acetylcholine-induced vasodilation. The increased levels of malondialdehyde and carbonyl protein were reduced by ASE. SOD, catalase, and glutathione peroxidase activities and the expressions of SOD1 and SOD2, eNOS, and TIMP-1 were decreased in 2K-1C rats and recovered by ASE. In 2K-1C rats, ASE prevented vascular remodeling and the increased expression/levels of MMP-2. These findings indicate that ASE produces antihypertensive effect and prevents the endothelial dysfunction and vascular structural changes in 2K-1C hypertension, probably through mechanisms involving antioxidant effects, NOS activation, and inhibition of MMP-2 activation.
Asunto(s)
Arecaceae/química , Hipertensión Renovascular/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Polifenoles/farmacología , Animales , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Presión Sanguínea/efectos de los fármacos , Western Blotting , Modelos Animales de Enfermedad , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Hipertensión Renovascular/fisiopatología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Extractos Vegetales/farmacología , Pletismografía , Polifenoles/aislamiento & purificación , Ratas , Ratas WistarRESUMEN
Nitric oxide (NO) is a short-lived intercellular messenger that provides an efficient vascular regulatory mechanism to support homeostasis and prevent thrombosis. Endothelial dysfunction and reduced NO bioavailability have a central role in hypertension associated with pregnancy. The purpose of this study was to investigate the impact of pregnancy on the L-arginine-NO-cGMP pathway in platelets and its correlation to platelet function and blood pressure in normotensive rats and spontaneously hypertensive rats (SHRs). Platelets were obtained from blood on the 20th day of pregnancy from female SHRs (SHR-P) and normotensive controls (P) or age-matched nonpregnant rats (SHR-NP and NP). Intraplatelet NO synthase (NOS) activity was reduced in P compared to NP, despite unchanged L-arginine influx. The expression levels of endothelial NOS (eNOS) and inducible NOS (iNOS) were diminished during pregnancy in normotensive rats. Paradoxically, cyclic guanosine monophosphate (cGMP) levels were similar between NP and P, as were phosphodiesterase type 5 (PDE5) expression and platelet aggregation induced by adenosine diphosphate. In SHRs, L-arginine influx was reduced in SHR-P compared to SHR-NP. SHR-P exhibited impaired NOS activity and reduced iNOS expression compared with SHR-NP. Soluble guanylyl cyclase and PDE5 expression in platelets were lower in SHR-P than in SHR-NP, whereas no differences were noted between groups with respect to cGMP levels. However, increased levels of cGMP were observed in SHR-P compared to normotensive groups and platelet aggregability remained unaltered. In conclusion, these observations prompted the hypothesis that normal platelet aggregation in pregnant SHRs may be related to a reduction in PDE5 expression and consequently the maintenance of cGMP levels, independently of reduced platelet NO bioavailability.
Asunto(s)
Arginina/metabolismo , GMP Cíclico/metabolismo , Hipertensión/metabolismo , Óxido Nítrico/metabolismo , Animales , Arginina/fisiología , Plaquetas/enzimología , GMP Cíclico/análisis , GMP Cíclico/fisiología , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/análisis , Femenino , Guanilato Ciclasa/análisis , Hipertensión/fisiopatología , Óxido Nítrico/fisiología , Óxido Nítrico Sintasa/análisis , Óxido Nítrico Sintasa de Tipo II/análisis , Óxido Nítrico Sintasa de Tipo III/análisis , Agregación Plaquetaria , Embarazo , Ratas , Ratas Endogámicas SHR , Ratas WistarRESUMEN
An alcohol-free grape-skin extract (GSE) obtained from skins of Vitis labrusca has significant anti-hypertensive, antioxidant and vasodilator effects. According to our previous results, the vasodilator effect of GSE in the isolated mesenteric vascular bed (MVB) of the rat is dependent on endothelium and partially dependent on nitric oxide (NO). In the MVB of the rat pre-contracted with norepinephrine (NE), bolus injections of GSE induced a long-lasting dose-dependent vasodilation that is significantly reduced after the treatment with 1H-[1,2,3] oxadiazolo [4,4-a] quinoxalin-1-one (ODQ). Additionally, in vessels pre-contracted with norepinephrine and depolarized with KCl (25 mM) or treated with Ca(2+)-dependent K(+)-channel blockers charybdotoxin (ChTx) plus apamin, the vasodilator effect of GSE was significantly reduced and almost abolished by ChTx plus apamin plus L-NAME. However, the vasodilator effect of GSE was unaffected by D-Arg[Hyp(3),Thi(5),D-Tic(7),Oic(8)]bradykinin (HOE-140), atropine, yohimbine, pyrilamine and 4-aminopyridine (4-AP). The vasoconstriction response elicited by bolus injection of KCl was not affected by GSE, whereas the vasoconstrictor response induced by NE was dose-dependently and completed inhibited by GSE in the presence but not in the absence of endothelium. However, NE-induced vasoconstriction in calcium-free condition or without endothelium was not reduced by GSE. The present results demonstrate that GSE induces a vasodilator effect in the rat MVB, which is dependent on NO in combination with endothelium-derived hyperpolarizing factor (EDHF). Additionally, our results indicated that extracellular Ca(2+) has an important role on the endothelium-dependent vasodilator effect induced by GSE.