RESUMO
Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology. Two different doses of RO and rosuvastatin, a cholesterol synthesis inhibitor used as a control, were orally administered. Disturbances in immune cellularity as well as lymphocyte proliferation and cytokine production were significantly normalized by oral administration of RO, which also decreased the elevated serum tumor necrosis factor (TNF)-α level and total cholesterol. The specific immune-related actions of RO comprised considerable improvement in cytotoxic T cell killing functions and regulation of antibody production to within the normal range. The immunological evidence confirms the significant cholesterol-lowering effect of RO, suggesting its potential as a novel therapeutic agent for hyperlipidemia and associated immune decline.
RESUMO
Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology. Two different doses of RO and rosuvastatin, a cholesterol synthesis inhibitor used as a control, were orally administered. Disturbances in immune cellularity as well as lymphocyte proliferation and cytokine production were significantly normalized by oral administration of RO, which also decreased the elevated serum tumor necrosis factor (TNF)-α level and total cholesterol. The specific immune-related actions of RO comprised considerable improvement in cytotoxic T cell killing functions and regulation of antibody production to within the normal range. The immunological evidence confirms the significant cholesterol-lowering effect of RO, suggesting its potential as a novel therapeutic agent for hyperlipidemia and associated immune decline.
Assuntos
Animais , Camundongos , Administração Oral , Envelhecimento , Formação de Anticorpos , Colesterol , Dieta , Dieta Hiperlipídica , Homicídio , Hiperlipidemias , Inflamação , Linfócitos , Camundongos Obesos , Fisiologia , Valores de Referência , Rosuvastatina Cálcica , Rubus , Fator de Necrose Tumoral alfaRESUMO
This study was designed to characterize the potential therapeutic effects of two statin drugs commonly used to treat dyslipidemia in inflammation-linked metabolic disorders related to type 2 diabetes. Atorvastatin (10 mg/kg/day) and rosuvastatin (3 mg/kg/day) were administered to mice with diet-induced obesity (DIO). The statins lowered serum total and LDL cholesterol levels, and improved the atherogenic index and cardiac risk index. Furthermore, the drugs decreased fasting glucose levels, improved glucose tolerance, and decreased fat tissue weight and adipocyte size; this was accompanied by an overall body weight loss tendency. The statins also improved antigen-specific immunity. The killing activity of cytotoxic T cells and exacerbation of IgG secretion levels were considerably normalized. Most importantly, serum tumor necrosis factor-α and interleukin 6 levels decreased, while their RNA expression levels in fat tissue were regulated by the statins as well. This study is the first to indicate that low doses of atorvastatin and rosuvastatin, the dosing regimen for which has been controversial, could significantly improve diabetes-related metabolic disorders, and could modulate pro-inflammatory cytokines, alleviating inflammation and simultaneously restoring overall humoral and cell-mediated immunity.