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1.
Nutrients ; 16(13)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38999848

RESUMEN

BACKGROUND: Our search for plant-derived ceramides from sustainable sources led to the discovery of ceramides and glucosylceramides in wine lees. OBJECTIVE: This study evaluated the efficacy and safety of wine lees extract (WLE)-derived ceramides and glucosylceramides in enhancing skin barrier function. METHODS: A randomized, double-blind, placebo-controlled study was conducted with 30 healthy Japanese subjects aged 20-64. Subjects were allocated to receive either the WLE-derived ceramides and glucosylceramides (test group) or placebo for 12 weeks. The primary outcome was transepidermal water loss (TEWL), and secondary outcomes included skin hydration, visual analog scale (VAS) of itching sensation, and the Japanese Skindex-29. RESULTS: One participant withdrew for personal reasons, resulting in 29 subjects for data analysis (placebo n = 15; test n = 14). The test group showed a tendency of lower TEWL compared to the placebo after 8 weeks (p = 0.07). Furthermore, after 12 weeks of administration, the test group had significantly lower TEWL than the placebo (p = 0.04). On the other hand, no significant differences were observed in the secondary outcome parameters. No adverse events related to the supplements were reported. CONCLUSIONS: Oral supplementation of WLE-derived ceramides and glucosylceramides is a prominent and safe approach to enhancing skin barrier function and health. TRIAL REGISTRATION: (UMIN000050422).


Asunto(s)
Ceramidas , Glucosilceramidas , Extractos Vegetales , Piel , Humanos , Método Doble Ciego , Adulto , Masculino , Femenino , Persona de Mediana Edad , Administración Oral , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Adulto Joven , Piel/efectos de los fármacos , Glucosilceramidas/administración & dosificación , Glucosilceramidas/farmacología , Vino/análisis , Pérdida Insensible de Agua/efectos de los fármacos
2.
Nutrients ; 15(7)2023 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-37049588

RESUMEN

A great number of chemically diverse pancreatic lipase (PL) inhibitors have been identified to tackle obesity; however, very few of them have entered clinical studies. The ethanolic extract of sesame meal is a potent PL inhibitor, and its activity hinges exclusively on two free fatty acids: linoleic acid and oleic acid, which were proven to reduce postprandial triglyceride excursion in rats. Herein, to investigate the clinical efficacy of the sesame meal extract, in a crossover trial, 30 healthy volunteers were randomized to receive the sesame meal extract containing experimental food or placebo along with a high-fat meal. Treatment with the sesame meal extract significantly lowered the incremental postprandial serum triglyceride concentration and reduced the incremental area under the curve (iAUC) by 16.8% (p-value = 0.03) compared to placebo. Significant decreases in postprandial remnant-like lipoprotein particle cholesterol and low-density lipoprotein particles were also observed, whereas high-density lipoprotein cholesterol was increased. These results suggest that treatment with the sesame meal extract significantly reduced the postprandial excursion of triglycerides and improved the lipidemic profile after high dietary fat intake in healthy individuals, indicating the substantial potential of free linoleic acid and oleic acid and natural products rich in these compounds for the management of obesity and related conditions.


Asunto(s)
Ácido Oléico , Sesamum , Animales , Ratas , Humanos , Estudios Cruzados , Ácido Oléico/farmacología , Ácido Linoleico/farmacología , Lipasa , Voluntarios Sanos , Triglicéridos , Colesterol , Obesidad , Periodo Posprandial , Grasas de la Dieta
3.
J Nutr Sci Vitaminol (Tokyo) ; 68(4): 331-341, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36047105

RESUMEN

Persimmon is a fruit rich in polyphenols (proanthocyanidins or condensed tannins). Using rats and humans, the effects of Kaki-tannin (Nara-type), persimmon polyphenols prepared using a new method, on postprandial plasma glucose levels were investigated in this study. Kaki-tannin (Nara-type) comprised mainly proanthocyanidins, composed of epicatechin : epicatechin gallate : epigallocatechin : epigallocatechin gallate in a ratio of 1 : 1 : 2 : 2 with a molecular weight of approximately 8,000 Da, with epicatechin gallate as a terminal unit. These polyphenols inhibited amylolytic enzymes, such as α-amylase, maltase, sucrase, and α-glucosidase in vitro, and sodium-dependent glucose transporter 1 in Caco-2 cells. These results suggested that the polyphenols suppressed digestion and absorption in the intestinal tract. The ingestion of 250 mg/kg body weight of the polyphenols significantly suppressed increased blood glucose levels after carbohydrate (2 g/kg body weight of glucose or maltose) loading in rats. In a human trial, 1.88 g of Kaki-tannin (Nara-type) significantly delayed increased plasma glucose levels after carbohydrate (150 kcal of maltooligosaccharides) loading. Thus, Kaki-tannin (Nara-type) holds promise to be developed as a food material that potentially improve blood glucose elevation after meals.


Asunto(s)
Diospyros , Proantocianidinas , Animales , Glucemia , Peso Corporal , Células CACO-2 , Frutas , Humanos , Polifenoles/farmacología , Proantocianidinas/farmacología , Ratas , Taninos/farmacología
4.
Sci Rep ; 12(1): 10300, 2022 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-35717470

RESUMEN

Acetaldehyde, a metabolic product of ethanol, induces DNA damage and genome instability. Accumulation of acetaldehyde due to alcohol consumption or aldehyde dehydrogenase (ALDH2) deficiency increases the risks of various types of cancers, including esophageal cancer. Although acetaldehyde chemically induces DNA adducts, the repair process of the lesions remains unclear. To investigate the mechanism of repair of acetaldehyde-induced DNA damage, we determined the repair pathway using siRNA knockdown and immunofluorescence assays of repair factors. Herein, we report that acetaldehyde induces DNA double-strand breaks (DSBs) in human U2OS cells and that both DSB repair pathways, non-homologous end-joining (NHEJ) and homology-directed repair (HDR), are required for the repair of acetaldehyde-induced DNA damage. Our findings suggest that acetaldehyde-induced DNA adducts are converted into DSBs and repaired via NHEJ or HDR in human cells. To reduce the risk of acetaldehyde-associated carcinogenesis, we investigated potential strategies of reducing acetaldehyde-induced DNA damage. We report that polyphenols extracted from persimmon fruits and epigallocatechin, a major component of persimmon polyphenols, attenuate acetaldehyde-induced DNA damage without affecting the repair kinetics. The data suggest that persimmon polyphenols suppress DSB formation by scavenging acetaldehyde. Persimmon polyphenols can potentially inhibit carcinogenesis following alcohol consumption.


Asunto(s)
Roturas del ADN de Doble Cadena , Diospyros , Acetaldehído/toxicidad , Aldehído Deshidrogenasa Mitocondrial/metabolismo , Carcinogénesis , Aductos de ADN , Reparación del ADN por Unión de Extremidades , Reparación del ADN , Frutas/metabolismo , Humanos , Polifenoles/farmacología
5.
Biosci Biotechnol Biochem ; 86(7): 875-883, 2022 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-35404447

RESUMEN

An increasing number of Japanese women of childbearing age are underweight (BMI <18.5), but the association between this and the increased number of low-birth-weight babies born remains unclear. Here, a rat model was established to mimic the undernutrition (85% of the energy required for those with normal activity levels) experienced by such women and to evaluate the associated impaired glucose tolerance. The undernourished Wistar rat group showed increased serum corticosterone level reflecting stress, and greater adrenal weight and size. It also showed greater insulin resistance, higher expression of FOXO-1, a transcription factor related to muscle atrophy, and lower expression of p-Akt, an insulin-dependent signaling factor. Overall, this work shows the key role of undernutrition during pregnancy as a cause of impaired glucose tolerance and increased diabetes risk in offspring. The findings of this study may inform preemptive measures to prevent the development of metabolic syndrome in offspring of undernourished mothers.


Asunto(s)
Intolerancia a la Glucosa , Desnutrición , Animales , Glucemia/metabolismo , Femenino , Humanos , Insulina , Japón , Desnutrición/complicaciones , Desnutrición/metabolismo , Embarazo , Ratas , Ratas Wistar , Delgadez
6.
J Nutr Sci Vitaminol (Tokyo) ; 67(5): 310-316, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34719616

RESUMEN

We investigated the effects of inadequate folate intake on the onset and progression of hypertensive organ injury. In the present study, 5-wk-old male stroke-prone spontaneously hypertensive rats (SHRSP) were fed with a normal-folate (control; 160-170 µg of folate/100 g diet) or low-folate (8-10 µg of folate/100 g diet) diet until they reached 25 wk of age. After the animals reached 10 wk of age, the bodyweight of the rats in the low-folate group was lower than that of the rats in the control group. Regarding blood pressure, both groups had severe hypertension of ≥230 mmHg at 12 wk of age that was not significantly different between the groups. At 16 wk of age, the low-folate group had a low number of blood cell types. The folate levels in the serum, liver, and kidneys of these rats were significantly lower (p<0.01) and the serum homocysteine level in the low-folate group was significantly higher than in the controls. The low-folate group had a significantly lower testicular weight than the control group (p<0.05) and arterial hypertrophy, spermatogenesis arrest, and interstitial connective tissue hyperplasia were observed. However, there was no clear difference in lesions in other organs. These results indicated that under low folate status, SHRSP causes hematopoietic disorders and exacerbates hypertensive vascular injury at various degrees by organ type.


Asunto(s)
Trastornos Cerebrovasculares , Hipertensión , Lesiones del Sistema Vascular , Animales , Presión Sanguínea , Ácido Fólico , Hipertensión/etiología , Masculino , Ratas , Ratas Endogámicas SHR
7.
Exp Physiol ; 102(11): 1435-1447, 2017 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-28841247

RESUMEN

NEW FINDINGS: What is the central question of this study? An inverse correlation between circulating adiponectin and many diseases has been reported, but some studies have found no correlation. To evaluate this controversy, we investigated the relationship between heart-bound adiponectin and hypertension or cardiac hypertrophy, compared with serum adiponectin. What is the main finding and its importance? Using hypertensive and normotensive rats, we found that heart-bound adiponectin was inversely correlated with cardiac hypertrophy, suggesting that heart-bound adiponectin has a more important function in preventing cardiac hypertrophy than circulating adiponectin. Our study provides new insights regarding the role of adiponectin in diseases. The inverse correlation between circulating adiponectin concentration and hypertension or cardiac hypertrophy is still controversial. In addition to circulating adiponectin, adiponectin is also bound to tissues such as the heart and skeletal muscle. In this study, we investigated the relationship of serum adiponectin and heart-bound adiponectin with hypertension and cardiac hypertrophy. Four types of hypertensive rats presenting different blood pressure levels were used at different ages, as follows: normotensive Wistar-Kyoto rats (WKYs); two sub-strains (strains C and B2, having low and high blood pressure, respectively) of spontaneously hypertensive rats (SHRs); and stroke-prone SHRs (SHRSPs). Blood pressure, heart-to-body weight ratio, serum adiponectin and heart-bound adiponectin were determined. Histopathological analysis of the heart was carried out to evaluate the relationship with heart-bound adiponectin. Serum adiponectin concentration was not inversely correlated with blood pressure or heart-to-body weight ratio. In contrast, heart-bound adiponectin levels were significantly lower in SHRSPs than in other strains at respective ages. This resulted from a decrease in T-cadherin expression, which induced adiponectin binding to tissues. No significant difference in heart-bound adiponectin among WKYs and SHRs (C and B2) was detected, indicating that heart-bound adiponectin is not related to hypertension. In addition, differences in heart-bound adiponectin did not affect AMP-activated protein kinase in the traditional adiponectin activation cascade. Histopathological analysis revealed that heart-bound adiponectin was inversely correlated with cardiomyocyte hypertrophy and left ventricular wall thickness and, in part, with cardiac fibrosis. These results suggest that the decreased level of heart-bound adiponectin in SHRSPs is more related to their cardiac hypertrophy than circulating adiponectin.


Asunto(s)
Adiponectina/sangre , Hipertensión/sangre , Hipertrofia Ventricular Izquierda/sangre , Miocardio/metabolismo , Accidente Cerebrovascular/etiología , Proteínas Quinasas Activadas por AMP/metabolismo , Acetil-CoA Carboxilasa/metabolismo , Adiponectina/genética , Factores de Edad , Animales , Biomarcadores/sangre , Presión Sanguínea , Cadherinas/metabolismo , Modelos Animales de Enfermedad , Fibrosis , Hipertensión/complicaciones , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/fisiopatología , Hipertrofia Ventricular Izquierda/prevención & control , Grasa Intraabdominal/metabolismo , Masculino , Miocardio/patología , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Función Ventricular Izquierda , Remodelación Ventricular
8.
Exerc Immunol Rev ; 21: 130-42, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25826051

RESUMEN

Thioredoxin (TRX) is a 12 kDa protein that is induced by oxidative stress, scavenges reactive oxygen species (ROS) and modulates chemotaxis. Furthermore it is thought to play a protective role in renal ischemia/reperfusion injury. Complement 5a (C5a) is a chemotactic factor of neutrophils and is produced after ischemia/reperfusion injury in the kidney. Both TRX and C5a increase after endurance exercise. Therefore, it may be possible that TRX has an association with C5a in renal disorders and/or renal protection caused by endurance exercise. Accordingly, the aim of this study was to investigate relationships among the changes of urine levels of TRX, C5a and acute kidney injury (AKI) caused by ischemia/reperfusion, inflammatory responses, and oxidative stress following intensive endurance exercise. Also, we applied a newly-developed measurement system of neutrophil migratory activity and ROS-production by use of ex vivo hydrogel methodology with an extracellular matrix to investigate the mechanisms of muscle damage. Fourteen male triathletes participated in a duathlon race consisting of 5 km of running, 40 km of cycling and 5 km of running were recruited to the study. Venous blood and urine samples were collected before, immediately following, 1.5 h and 3 h after the race. Plasma, serum and urine were analyzed using enzyme-linked immunosorbent assays, a free radical analytical system, and the ex vivo neutrophil functional measurement system. These data were analyzed by assigning participants to damaged and minor-damage groups by the presence and absence of renal tubular epithelial cells in the urinary sediments. We found strong associations among urinary TRX, C5a, interleukin (IL)-2, IL-4, IL-8, IL-10, interferon (IFN)-γ and monocyte chemotactic protein (MCP)-1. From the data it might be inferred that urinary TRX, MCP-1 and ß-N-acetyl-D-glucosaminidase (NAG) were associated with renal tubular injury. Furthermore, TRX may be influenced by levels of IL-10, regulate chemotactic activity of C5a and IL-8, and control inflammatory progress by C5a and IL-8. In the longer duration group (minor-damage group), circulating neutrophil count, plasma concentration of myeloperoxidase (MPO) and serum concentration of myoglobin were markedly increased. In the higher intensity group (damaged group), neutrophil activation and degranulation of MPO might be inhibited, because not only was ROS production observed to be higher, but also antioxidant capacity and antiinflammatory cytokines were increased. Critically, the newlydeveloped ex vivo methodology corroborated the neutrophil activation levels in the two groups of participants.


Asunto(s)
Lesión Renal Aguda/etiología , Citocinas/orina , Ejercicio Físico/fisiología , Inflamación/etiología , Músculo Esquelético/lesiones , Estrés Oxidativo , Tiorredoxinas/orina , Lesión Renal Aguda/orina , Adulto , Atletas , Ciclismo/fisiología , Biomarcadores/orina , Citocinas/sangre , Terapia por Ejercicio , Humanos , Inflamación/orina , Fallo Renal Crónico/terapia , Masculino , Neutrófilos/enzimología , Neutrófilos/fisiología , Peroxidasa/sangre , Resistencia Física/fisiología , Daño por Reperfusión/etiología , Daño por Reperfusión/orina , Carrera/fisiología , Adulto Joven
9.
Life Sci ; 120: 48-53, 2015 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-25445217

RESUMEN

AIMS: To determine the prophylactic effects of an elastin peptide derived from the bulbus arteriosus of bonitos and prolylglycine (PG), a degradation product of elastin peptide, on vascular dysfunction in spontaneously hypertensive rats (SHRs). MAIN METHODS: Male 15-week-old SHR/Izm rats were fed without (control group) or with elastin peptide (1 g/kg body weight) for 5 weeks (EP group), or were infused via an osmotic mini-pump for 4 weeks with PG (PG group) or saline (control group). Using thoracic aortas, we assessed endothelial changes by scanning electron microscopy. Vascular reactivity (contraction and relaxation) and pressure-induced distension was compared. mRNA production levels of endothelial nitric oxide synthase (eNOS) and intercellular adhesion molecule-1 (ICAM-1) were investigated by real-time-polymerase chain reaction. KEY FINDINGS: Aortas of the EP group displayed limited endothelial damage compared with that in the control group. Under treatment of SHRs with elastin peptide, the effect of phenylephrine returned closer to the normal level observed in normotensive Wistar-Kyoto (WKY/Izm) rats. mRNA production of eNOS (but not ICAM-1) was greater in the EP group than in the control group. Endothelial damage was suppressed and pressure-induced vascular distension was greater in the PG group than in the corresponding control group. SIGNIFICANCE: These results suggest that elastin peptide from bonitos elicits prophylactic affects hypertension-associated vascular dysfunction by targeting the eNOS signaling pathway. PG may be a key mediator of the beneficial effects of elastin peptide.


Asunto(s)
Aorta Torácica/patología , Dipéptidos/química , Elastina/química , Endotelio/efectos de los fármacos , Enfermedades Vasculares/tratamiento farmacológico , Animales , Fenómenos Biomecánicos , Presión Sanguínea/efectos de los fármacos , Endotelio/ultraestructura , Peces , Molécula 1 de Adhesión Intercelular/metabolismo , Masculino , Microscopía Electrónica de Rastreo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Reacción en Cadena en Tiempo Real de la Polimerasa
10.
Exerc Immunol Rev ; 19: 29-48, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23977718

RESUMEN

It has been consistently shown that circulating levels of interleukin (IL)-6, IL-8, IL-1 receptor antagonist (IL-1ra) and IL-10 increase remarkably following endurance exercise longer than 2 h such as marathon and triathlon races. However, no studies have compared changes in the plasma and urinary levels of these cytokines after endurance exercise, including the recovery period. In the present study, we investigated kinetic changes in the urinary excretion of cytokines following endurance exercise up to 3 h after exercise to evaluate the magnitude of change in comparison to the plasma levels and to explore the possible biological significance and the mechanisms of cytokine dynamics following exercise. Fourteen male athletes participated in a duathlon race consisting of 5 km of running, 40 km of cycling, and 5 km of running. Venous blood and urine samples were collected before, immediately after, 1.5 h and 3 h after the race. Plasma and urine were analyzed using enzyme-linked immunosorbent assays (ELISA). Plasma concentrations of lL-1beta, IL-1ra, IL-6, IL-8, IL-10 and monocyte chemotactic protein (MCP)-1 increased significantly after the race, whereas tumour necrosis factor (TNF)-alpha, IL-2, IL-4, IL-12 and interferon (IFN)-gamma did not change significantly. Urinary concentrations of lL-1beta, IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IFN-gamma and MCP-1 increased significantly after the race. When the urine concentrations were adjusted by creatinine concentration, urine volume and sampling time, the increases of lL-2, IL-4, IL-8, IL-10, IFN-gamma and MCP-1 were evident and these were notably present in urine of the stressed athletes suffering from renal tubular epithelial damage. The present study provides new evidence that the kinetics and magnitude of changes in urinary cytokine concentrations differ from plasma cytokine concentrations following endurance exercise, especially, in the recovery period several hours after exercise, and that the damaged kidney might be responsible at least in part for the kinetics of some cytokines. Urinary cytokines may be sensitive biomarkers of the impact of exhaustive exercise workload on renal damage and inflammation in the recovery period after endurance exercise.


Asunto(s)
Atletas , Citocinas/sangre , Citocinas/orina , Carrera/fisiología , Adulto , Ensayo de Inmunoadsorción Enzimática , Humanos , Masculino , Esfuerzo Físico/inmunología
11.
Microvasc Res ; 90: 169-72, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23978333

RESUMEN

To elucidate the pathogenic roles of oxidative stress on blood-brain-barrier (BBB) dysfunction, we compared the chronological changes of oxidative stress in blood and cerebral tissue between stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Plasma and tissue oxidative stress was assayed by the diacron-reactive oxygen metabolite (d-ROM) test using 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a reference oxidative stress marker. The plasma and cerebral cortex d-ROM levels increased in SHRSP after 16weeks of age, but not in WKY. There were no significant differences in 8-OHdG or lipid peroxidation markers between SHRSP and WKY. Antioxidant capacity, as estimated by the biological antioxidant potential test, was similar between SHRSP and WKY at all ages examined. The changes in plasma and tissue d-ROM levels coincided with changes in glucose transporter-1 and aquaporin-4 expression, as functional constituents of the BBB. These results indicate that plasma oxidative stress increases before the onset of tissue damage, and plays an important role in BBB dysfunction rather than decreases in antioxidant capacity. The plasma d-ROM test appears to be useful for predicting vasogenic cerebral edema in severe hypertension.


Asunto(s)
Barrera Hematoencefálica/metabolismo , Edema Encefálico/etiología , Permeabilidad Capilar , Hipertensión/complicaciones , Estrés Oxidativo , Accidente Cerebrovascular/etiología , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Acuaporina 4/metabolismo , Biomarcadores/metabolismo , Presión Sanguínea , Barrera Hematoencefálica/fisiopatología , Peso Corporal , Edema Encefálico/metabolismo , Edema Encefálico/fisiopatología , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Modelos Animales de Enfermedad , Transportador de Glucosa de Tipo 1/metabolismo , Hipertensión/metabolismo , Hipertensión/fisiopatología , Peroxidación de Lípido , Masculino , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/fisiopatología , Factores de Tiempo
12.
Biosci Biotechnol Biochem ; 77(8): 1689-93, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23924731

RESUMEN

Oxidative stress was induced in 12-week-old offspring of protein-restricted (9% protein) and control (20% protein) protein-restricted stroke-prone spontaneously hypertensive rats (SHRSP) by administering phorbol 12-myristate 13-acetate (PMA) for 4 weeks to determine the effects of oxidative stress on the vascular function of the SHRSP offspring. There was no significant difference in the blood pressure of offspring of the protein-restricted dams and control dams. The plasma diacron-reactive oxygen metabolite (dROM) level at 16 weeks of age was significantly higher in offspring of the protein-restricted dams, whereas the anti-oxidative enzyme activity was similar in both groups. Acetylcholine (Ach)-induced relaxation was significantly reduced in offspring of the protein-restricted dams. The expression of endothelial nitric oxide synthase (eNOS) was lower and the expression of soluble guanylic acid cyclase (sGC) was higher in offspring of the protein-restricted dams. These results indicate that SHRSP offspring of the protein-restricted dams were sensitive to oxidative stress, and displayed the vascular dysfunction.


Asunto(s)
Dieta con Restricción de Proteínas , Endotelio Vascular/efectos de los fármacos , Hipertensión/metabolismo , Estrés Oxidativo , Animales , Endotelio Vascular/fisiopatología , Regulación de la Expresión Génica/efectos de los fármacos , Guanilato Ciclasa/biosíntesis , Hipertensión/inducido químicamente , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/biosíntesis , Ratas , Especies Reactivas de Oxígeno/metabolismo , Acetato de Tetradecanoilforbol/administración & dosificación , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología
13.
Exerc Immunol Rev ; 18: 116-27, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22876724

RESUMEN

The T-cell subset Th17 is induced partly by interleukin (IL)-6 and activated by IL-23, and produces a proinflammatory cytokine IL-17. Since IL-6 increases dramatically following long-lasting endurance exercise, this response may also stimulate the induction of IL-17 and IL-23 after exercise. The aim of this study was to clarify the dynamics of IL-17 in association with endurance exercise-induced muscle damage and inflammatory responses. Fourteen male triathletes participated in a duathlon race consisting of 5 km of running, 40 km of cycling and 5 km of running. Venous blood and urine samples were collected before, immediately after 1.5 h and 3 h after the race. Plasma and urine were analyzed using enzyme-linked immunosorbent assays (ELISA). Haematological and biochemical variables such as neutrophil activation marker (myeloperoxidase: MPO), muscle damage marker (myoglobin: Mb) and soluble receptor activator of nuclear factor (NF)-KB ligand (sRANKL) were also determined to estimate the biological and pathological significance. Plasma concentrations oflL-6 (+26.0x), MPO (+3.2x) and Mb (+4.9x) increased significantly immediately after the race and IL-17 and IL-23 tended to increase. Furthermore, plasma concentrations of IL-12p40 and sRANKL increased significantly after the race. The measured parameters related to Thl 7 cytokines in the urinary output were closely correlated with each other and muscle damage marker. These findings suggest that IL-17 induced by IL-6 and activated by IL-23 or other IL-17 producing-cells and IL-23 might promote neutrophil activation and muscle damage following prolonged endurance exercise.


Asunto(s)
Interleucina-17/inmunología , Músculo Esquelético/inmunología , Activación Neutrófila , Resistencia Física/inmunología , Células Th17/inmunología , Adulto , Ensayo de Inmunoadsorción Enzimática , Ejercicio Físico/fisiología , Humanos , Subunidad p40 de la Interleucina-12/sangre , Subunidad p40 de la Interleucina-12/orina , Interleucina-17/sangre , Interleucina-17/orina , Interleucina-23/sangre , Interleucina-23/inmunología , Interleucina-23/orina , Interleucina-6/sangre , Interleucina-6/inmunología , Interleucina-6/orina , Masculino , Músculo Esquelético/lesiones , Mioglobina/sangre , Mioglobinuria/inmunología , Peroxidasa/sangre , Peroxidasa/orina , Receptor Activador del Factor Nuclear kappa-B/sangre , Receptor Activador del Factor Nuclear kappa-B/orina
14.
Food Funct ; 3(4): 389-98, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22307524

RESUMEN

Hesperetin is an aglycone of citrus flavonoids and is expected to exert a vasodilatation effect in vivo. We developed water-dispersible hesperetin by the process of micronization to enhance the bioavailability of hesperetin. This study aimed to assess the effect of this process on the bioavailability of hesperetin and to estimate its efficiency on vasodilatation-related functions using endothelial cells in vitro and a human volunteer study at a single dose in vivo. We found that water-dispersible hesperetin was absorbed rapidly, with its maximum plasma concentration (C(max)) being 10.2 ± 1.2 µM, and that the time to reach C(max), which is within 1 h if 150 mg of this preparation was orally administered in humans. LC-MS analyses of the plasma at C(max) demonstrated that hesperetin accumulated in the plasma as hesperetin 7-O-ß-D-glucuronide (Hp7GA), hesperetin 3'-O-ß-D-glucuronide (Hp3'GA) and hesperetin sulfate exclusively. Similar to hesperetin, Hp7GA enhanced nitric oxide (NO) release by inhibiting nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) activity in a human umbilical vein endothelial cell culture system, indicating that plasma hesperetin metabolites can improve vasodilatation in the vascular system. A volunteer study using women with cold sensitivity showed that a single dose of water-dispersible hesperetin was effective on peripheral vasodilatation.These results strongly suggest that rapid accumulation with higher plasma concentration enables hesperetin to exert a potential vasodilatation effect by the endothelial action of its plasma metabolites. Water-dispersible hesperetin may be useful to improve the health effect of dietary hesperetin.


Asunto(s)
Hesperidina/farmacocinética , Células Endoteliales de la Vena Umbilical Humana/fisiología , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacocinética , Administración Oral , Adolescente , Adulto , Disponibilidad Biológica , Circulación Sanguínea/efectos de los fármacos , Temperatura Corporal/efectos de los fármacos , Femenino , Hesperidina/administración & dosificación , Hesperidina/sangre , Hesperidina/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Vasodilatadores/administración & dosificación , Vasodilatadores/sangre , Vasodilatadores/metabolismo , Adulto Joven
15.
Biorheology ; 49(5-6): 353-63, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23380901

RESUMEN

Many people are sensitive to cold, resulting in poor blood circulation. There is evidence that hesperidin results in increased peripheral circulation and skin temperature. A transglycosylated hesperidin, α-glucosylhesperidin, is more bioabsorbable than hesperidin. In the present study, biomechanical studies were performed on the effects of long-term feeding of α-glucosylhesperidin on the contractile response (diameter response) and stiffness of femoral arteries excised from rabbits. Animals in the normal (non-treated), low, and high groups were fed 0, 150 and 4500 mg/day, respectively, of α-glucosylhesperidin for about 24 weeks. The feeding of α-glucosylhesperidin did not change arterial stiffness nor mean blood flow rate in the femoral artery; however, it increased mean aortic blood pressure and decreased arterial diameter at 100 mmHg in the high group. The diameter responses developed by 10-5 M of norepinephrine were significantly lower in the high and low groups than in non-treated group. This result indicates that, due to the long-term feeding of α-glucosylhesperidin, arterial contraction induced by the neurotransmitter of sympathetic nerves decreases. It was estimated that blood flow in such muscular arteries as the femoral artery is maintained at normal by α-glucosylhesperidin even under the conditions of autonomic imbalance and cold intolerance.


Asunto(s)
Presión Arterial/efectos de los fármacos , Arteria Femoral/fisiología , Glucósidos/farmacología , Hesperidina/análogos & derivados , Hesperidina/farmacología , Animales , Fenómenos Biomecánicos , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Femenino , Glucósidos/química , Hesperidina/química , Norepinefrina/farmacología , Conejos , Rigidez Vascular/efectos de los fármacos , Vasoconstrictores/farmacología
16.
Biosci Biotechnol Biochem ; 75(8): 1608-10, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21821945

RESUMEN

Hesperetin, the aglycone of hesperidin present in citrus fruits, possesses various biological activities. We assessed the tissue distribution of hesperetin in rats fed with a 0.2% hesperetin diet for 4 weeks. Its highest concentration was found in the liver, and the second highest was in the aorta. The aorta is assumed to be one of the main target tissues of hesperetin for exerting its functions.


Asunto(s)
Aorta/química , Citrus/química , Hesperidina/metabolismo , Animales , Disponibilidad Biológica , Permeabilidad Capilar/efectos de los fármacos , Enfermedades Cardiovasculares/dietoterapia , Enfermedades Cardiovasculares/fisiopatología , Cromatografía Líquida de Alta Presión , Dieta , Hesperidina/administración & dosificación , Hesperidina/sangre , Hesperidina/farmacocinética , Hígado/química , Masculino , Ratas , Ratas Wistar , Distribución Tisular
17.
Biosci Biotechnol Biochem ; 74(4): 707-15, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20378967

RESUMEN

We studied the effects of alpha-glucosylhesperidin (G-Hsp) on the peripheral body temperature and autonomic nervous system in humans. We first conducted a survey of 97 female university students about excessive sensitivity to the cold; 74% of them replied that they were susceptible or somewhat susceptible to the cold. We subsequently conducted a three-step experiment. In the first experiment, G-Hsp (500 mg) was proven to prevent a decrease in the peripheral body temperature under an ambient temperature of 24 degrees C. In the second experiment, a warm beverage containing G-Hsp promoted blood circulation and kept the finger temperature higher for a longer time. We finally used a heart-rate variability analysis to study whether G-Hsp changed the autonomic nervous activity. The high-frequency (HF) component tended to be higher, while the ratio of the low-frequency (LF)/HF components tended to be lower after the G-Hsp administration. These results suggest that the mechanism for temperature control by G-Hsp might involve an effect on the autonomic nervous system.


Asunto(s)
Sistema Nervioso Autónomo/fisiología , Frío , Sistema Nervioso Autónomo/efectos de los fármacos , Electrocardiografía , Femenino , Humanos , Adulto Joven
18.
Neurosci Lett ; 461(1): 30-5, 2009 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-19497350

RESUMEN

Changes in the activity of the autonomic nervous system are good indicators of alterations in physiological phenomena such as the body temperature, blood glucose, blood pressure. Hesperidin, a flavanone known as vitamin P, has been shown to reduce the levels of serum lipids, cholesterol, and blood pressure. However, hesperidin is not water-soluble and is not well absorbed from the intestine. G-hesperidin (4G-alpha-glucopyranosyl hesperidin) is more water-soluble and more rapidly absorbed than hesperidin. In order to clarify the functions of G-hesperidin, we examined the effects of oral administration of G-hesperidin on interscapular brown adipose tissue-sympathetic nerve activity (BAT-SNA) and cutaneous sympathetic nerve activity (CASNA) in rats weighing about 300 g. In this study, we found that oral administration of 60 mg of G-hesperidin increased the BAT-SNA but decreased the CASNA in urethane-anesthetized rats. Since an elevation in BAT-SNA increases heat production (i.e. body temperature (BT)) and a decrease in CASNA increases cutaneous perfusion, we examined whether oral administration of G-hesperidin had an effect on the peripheral BT in rats. Consequently, we observed that the subcutaneous BT at the caudal end of the back after oral administration of 60 mg of G-hesperidin was significantly higher than the subcutaneous BT after oral administration of water in conscious rats. These findings suggest that G-hesperidin enhances the BAT-SNA and suppresses the CASNA resulting in an increase in the peripheral BT, probably by an increase in the thermogenesis in the BAT and an elevation in the cutaneous blood flow.


Asunto(s)
Tejido Adiposo Pardo/inervación , Temperatura Corporal/efectos de los fármacos , Hesperidina/análogos & derivados , Hesperidina/farmacología , Piel/inervación , Sistema Nervioso Simpático/efectos de los fármacos , Administración Oral , Animales , Hesperidina/administración & dosificación , Masculino , Ratas , Ratas Wistar
19.
Free Radic Biol Med ; 45(9): 1318-25, 2008 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-18775490

RESUMEN

The oxidative formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA is closely associated with the induction of degenerative diseases, including cancer. However, the oxidant species participating in the formation of 8-OHdG has yet to be fully clarified. On the basis that peroxyl radicals are a strong candidate for this species, we employed 2,2'-azobis(2-amidinopropane) (AAPH) as a peroxyl radical generator. Exposure of calf thymus DNA to AAPH formed 8-OHdG, but the exposure of 2'-deoxyguanosine (dG) alone did not. From the exposure of various combinations of nucleotides, 8-OHdG was formed only in the presence of dG and thymidine (dT). A mix of dG with an oxidation product of dT, 5-(hydroperoxymethyl)-2'-deoxyuridine, produced 8-OHdG, but the amount formed was small. In contrast, 8-OHdG was produced abundantly by the addition of dG to peroxidized dT with AAPH. Thus, the formation of 8-OHdG was mediated by the peroxidized dT. Instead of artificial AAPH, endogenous peroxyl radicals are known to be lipid peroxides, which are probably the oxidant species for 8-OHdG formation mediated by thymidine in vivo.


Asunto(s)
Desoxiguanosina/análogos & derivados , Timidina/farmacología , 8-Hidroxi-2'-Desoxicoguanosina , Amidinas/química , Animales , Bovinos , Desoxiguanosina/química , Desoxiguanosina/metabolismo , Dimerización , Mitocondrias/metabolismo , Modelos Químicos , Oxidantes/química , Oxígeno/química , Peróxidos , Especificidad por Sustrato , Timidina/química , Factores de Tiempo
20.
Immunopharmacol Immunotoxicol ; 30(1): 117-34, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18306109

RESUMEN

Hesperidin (Hsp) is an abundant flavonoid in citrus fruits, and the oral administration of Hsp has been recently reported to suppress collagen-induced arthritis in mice. Therefore, we sought to determine whether alpha-glucosylhesperidin (Hsp-G), which is an Hsp derivative with enhanced water-solubility, is effective on treating arthritis in both mice and humans. Hsp-G was orally administered to mice with collagen-induced arthritis, and its effects were evaluated clinically and histologically. Oral administration of Hsp-G improved collagen-induced arthritis when administered before the onset of arthritis as well as when administered after its onset. A decrease in tumor necrosis factor-alpha production was found to cause this improvement. In the human study, 19 patients with rheumatoid arthritis (RA) were enrolled in a 12-week double-blind, placebo-controlled trial. Patients were administered beverages containing 3 g Hsp-G (n = 9) or placebo (n = 10) every morning for the duration of the 3-month trial. Additionally, patients received standard therapy from a physician every 4 weeks. As a result, 3 of 9 patients in the Hsp-G group improved, while only 1 of 10 patients in the placebo group improved; this was in accordance with the American College of Rheumatology criteria. The present study revealed that the food material Hsp-G was effective when administered with standard anti-rheumatoid therapy in ameliorating RA in mice and humans without any adverse effects and may improve the quality of life for patients with RA as a complementary/alternative medicine.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Glucósidos/uso terapéutico , Hesperidina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antirreumáticos/química , Artritis Experimental/patología , Artritis Reumatoide/patología , Citrus/química , Método Doble Ciego , Femenino , Alimentos , Glucósidos/química , Hesperidina/química , Hesperidina/uso terapéutico , Humanos , Articulación de la Rodilla/patología , Masculino , Ratones , Ratones Endogámicos DBA , Persona de Mediana Edad , Placebos , Resultado del Tratamiento
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