Proposta de duas novas terapêuticas, extrato aquoso de Chrysobalanus icaco e rutina, em modelos experimentais de obesidade e resistência à insulina

• Autor(a) principal: White, Pollyanna Alves Secundo
• Data de Publicação: 2015
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UFS
• Texto Completo: https://ri.ufs.br/handle/riufs/3597
• topic: Obesidade; Diabetes tipo 2; Chrysobalanus icaco; N2a; Rutina; Obesity; Type 2 diabetes; Chrysobalanus icaco; N2a; Rutin; CNPQ::CIENCIAS DA SAUDE

Adiposity is a severe risk factor and it´s directly related to the development of several chronic diseases, especially obesity and type 2 diabetes. Numerous trials have been conducted to find and develop new anti-obesity drugs through herbal sources to minimize adverse reactions associated with the present drugs used for obesity and type 2 diabetes treatment. Researches conducted with the aqueous extract of Chrysobalanus icaco L (AECI) have demonstrated decrease in blood glucose levels and prevention of weight gain and fat accumulation in mice liver. The aim of this thesis was to develop new study basis for the development of new therapies and investigate the role of AECI and rutin in the treatment of obesity and type 2 diabetes. The first chapter addresses the action of AECI on the adipose and glycemic profile of obese mice high-fat diet induced. To this end, a group of 34 male C57BL/6J mice were randomly assigned to standard chow or high-fat diet and and further treated with the AECI in two concentrations, 0,35 mg/mL e 0,7 mg/mL. Food intake, feed efficiency, metabolic efficiency, body weight, fat pads weight, serum lipid, fecal lipid excretion, locomotor activity and insulin and glucose sensitivity were evaluated at the end of the 14 weeks of experiment. Results showed that the AECI in the lower concentration increased locomotor activity (p<0.01) and lean mass (p<0.05), decreased fat mass gain (p<0.01), TG levels (p<0.05), and fecal lipid excretion (p<0.01), and normalized insulin (p<0.05) and glucose sensitivity (p<0.05). On the other hand, the AECI in the higher concentration increased food intake (p <0.0001 vs. SC SCA p <0.0001 vs. HFA2 HFD) and the feed efficiency (p <0.05 vs. SC SCA p <0.05 vs. HFA2 HFD), hindering the loss of the body fat and glucose homeostasis. These findings indicates that AECI in lower doses can prevent fat storage or enhance fat utilization, in part, due to the increase of locomotor activity, favoring the glucose homeostasis through the normalization of insulin sensitivity and glucose tolerance. These effects may be related to the antioxidant activity and polyphenol content of the extract. The second chapter addresses the development of a model of insulin resistance TNF-α induced in neuron cells. In this study N2a were treated for 30 minutes with TNF-α, rutin or vehicle and then stimulated with insulin for 15 minutes. The protein lysate was extracted and total and p-Akt were measured, as well as total IkBα through Western blot. Results showed degradation of total IkBα protein in 64.2% (p<0.05) and significant decrease on p-Akt of 36.1% (p<0.001). The rutin, on the other hand, wasn´t able to prevent NF-κB activation, however, it tended to minimize the attenuation of Akt phosphorylation induced by the TNF- α. These findings indicates that TNF-α generated a N2a model of inflammation induced insulin resistance. Furthermore, rutin can contribute with the Akt activation reducing TNF- α damage in these cells.