RESUMO
BACKGROUND: High-fat, high-carbohydrate (HFHC) meals are known to induce oxidative and inflammatory stress, an increase in plasma endotoxin concentrations, and an increase in the expression of suppressor of cytokine signaling-3 (SOCS-3). HYPOTHESIS: The intake of a nutritional supplement containing resveratrol and muscadine grape polyphenols reduces HFHC meal-induced oxidative and inflammatory stress and stimulates the activity of the antioxidant transcription factor, NF-E2-related factor-2 (Nrf-2), and its downstream targets. METHODS: Ten normal, healthy subjects were given a 930-kcal HFHC meal either with placebo or with the supplement. Indices of oxidative stress, inflammation, Nrf-2 binding activity, the concentrations of endotoxin (lipopolysaccharide) and lipoprotein binding protein (LBP), and the expression of toll-like receptor 4 (TLR-4), CD14, IL-1ß, TNFα, SOCS-3, Keap-1, NAD(P)H:quinone oxidoreductase-1 (NQO-1), and GST-P1 were measured. RESULTS: The intake of the supplement suppressed the meal-induced elevations of plasma endotoxin and LBP concentrations, the expression of p47(phox), TLR-4, CD14, SOCS-3, IL-1ß, and Keap-1, while enhancing Nrf-2 binding activity and the expression of NQO-1 and GST-P1 genes. CONCLUSION: A supplement containing resveratrol and muscadine polyphenols suppresses the increase in oxidative stress, lipopolysaccharide and LBP concentrations, and expression of TLR-4, CD14, IL-1ß and SOCS-3 in mononuclear cells after an HFHC meal. It also stimulates specific Nrf-2 activity and induces the expression of the related antioxidant genes, NQO-1 and GST-P1. These results demonstrate the acute antioxidant and antiinflammatory effects of resveratrol and polyphenolic compounds in humans in the postprandial state.
Assuntos
Antioxidantes/farmacologia , Carboidratos da Dieta/farmacologia , Gorduras na Dieta/efeitos adversos , Flavonoides/farmacologia , Inflamação/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Estilbenos/farmacologia , Adulto , Western Blotting , Citocinas/biossíntese , DNA/biossíntese , DNA/genética , Fallopia japonica/química , Feminino , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Receptores de Lipopolissacarídeos/biossíntese , Lipopolissacarídeos/farmacologia , Masculino , Fator 2 Relacionado a NF-E2/biossíntese , Extratos Vegetais/farmacologia , Polifenóis , Resveratrol , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/biossíntese , Receptor 4 Toll-Like/biossíntese , Vitis/químicaRESUMO
BACKGROUND: Resveratrol have been shown to exert an antiinflammatory and antiaging effects in vitro and in animal models. OBJECTIVE: The objective of the study was to investigate the effect of a Polygonum cuspidatum extract (PCE) containing resveratrol on oxidative and inflammatory stress in normal subjects. RESEARCH DESIGN AND METHODS: Two groups (10 each) of normal-weight healthy subjects were randomized to placebo or PCE containing 40 mg resveratrol daily for 6 wk. Fasting blood samples were obtained prior to and after treatment at 1, 3, and 6 wk. Mononuclear cells were prepared for reactive oxygen species generation, RNA isolation, nuclear extract, and total cell homogenate preparation. Indices of oxidative and inflammatory stress, suppressor of cytokine signaling-3, phosphotyrosine phosphatase-1B, jun-N-terminal kinase-1, and inhibitor of kappaB-kinase-beta were measured by RT-PCR and Western blotting. RESULTS: The extract induced a significant reduction in reactive oxygen species generation, the expression of p47(phox), intranuclear nuclear factor-kappaB binding, and the expression of jun-N-terminal kinase-1, inhibitor of kappaB-kinase-beta, phosphotyrosine phosphatase-1B, and suppressor of cytokine signaling-3 in mononuclear cells when compared with the baseline and the placebo. PCE intake also suppressed plasma concentrations of TNF-alpha, IL-6, and C-reactive protein. There was no change in these indices in the control group given placebo. CONCLUSIONS: The PCE-containing resveratrol has a comprehensive suppressive effect on oxidative and inflammatory stress.
Assuntos
Anti-Inflamatórios/farmacologia , Fallopia japonica , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Estilbenos/farmacologia , Adulto , Antioxidantes/química , Antioxidantes/farmacologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Citocinas/genética , Citocinas/metabolismo , Fallopia japonica/química , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Insulina/sangue , Leptina/sangue , Lipídeos/sangue , Estresse Oxidativo/efeitos dos fármacos , Placebos , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Resveratrol , Estilbenos/químicaRESUMO
Whipple's disease is a rare, chronic, multi-systemic infectious disorder caused by the bacterium, Tropheryma whipplei. Relapses are commonly associated with neurological symptoms. We report a case of a 55-year-old man who presented with symptoms of progressive headache, 13 years after apparent complete recovery from intestinal Whipple's disease. Studies showed hydrocephalus with obstruction of the aqueduct and cerebrospinal fluid findings consistent with chronic meningitis. Diagnosis of central nervous system Whipple's disease was confirmed by analysis of the cerebrospinal fluid using polymerase chain reaction. After one year of antibiotic therapy, symptoms resolved and cerebrospinal fluid pleocytosis had improved. This case illustrates that Whipple's disease should be included in the differential diagnosis of central nervous system disorders as it is a potentially treatable cause of chronic meningitis. Failure to recognize this presentation can lead to misdiagnosis or a significant delay in diagnosis and treatment.
