RESUMO
Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia. Although the clear mechanisms of DM and insulin resistance are still to be cleared, it has been well documented that reactive oxygen species (ROS) play a pivotal role in DM and multiple types of insulin resistance. For the past few years, natural substances have been shown to have the potential to treatment DM. Attention has been especially focused on plants rich in triterpenoids, which generally show antioxidant and antiglycation effect. In our previous studies, it was shown that oleanolic acid (OA), a natural triterpenoid and an aglycone of many saponins, is a potent antioxidant acting as not only a free radical-scavenger through direct chemical reactions but also as a biological molecule, which may enhance the antioxidant defenses. The present study aimed to investigate the potential antidiabetic effect of OA. Oleanolic acid showed a significant blood glucose-lowering and weight-losing effect in diabetic animals induced by streptozotocin (STZ). In the insulin resistant model, it was also shown that OA may promote insulin signal transduction and inhibit oxidative stress-induced hepatic insulin resistance and gluconeogenesis, in which process the phosphorylation of ERK and the protective effect on mitochondrial function may be involved. These findings may significantly better the understanding of the pharmacological actions of OA and advance therapeutic approaches to DM.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Ácido Oleanólico/farmacologia , Animais , Antioxidantes/farmacologia , Glicemia/efeitos dos fármacos , Linhagem Celular , Hepatócitos/efeitos dos fármacos , Humanos , Insulina/metabolismo , Resistência à Insulina , Masculino , Potencial da Membrana Mitocondrial , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Adriamycin is an effective anthracycline anti-tumor antibiotic. However, the clinical use of adriamycin has been restricted by its serious side effects. Some reports indicated that the side effects of adriamycin could cause systemic injury, in which reactive oxygen species (ROS) play an important role. ROS are a large family of oxygen free radical and non-free radical active oxygen-containing molecules, including superoxide radical, hydrogen peroxide and hydroxyl radical, which contribute to oxidative stress. Although antioxidant treatment is a promising method to prevent the side effects, protection by a single antioxidant is limited. The Chinese herbal medicine ANTIOXIN is a multiple antioxidant that can effectively block oxidative stress. It was hypothesized that ANTIOXIN could effectively reduce the side effects of adriamycin. A rat tumor model with a transplanted tumor in the liver was treated with adriamycin and ANTIOXIN was used as a protection. Oxidative stress and antioxidant enzymes were evaluated. The results showed that adriamycin chemotherapy increased the level of malondialdehyde (MDA), nitrogen oxide (NO) and decreased the activities of total superoxide dismutase (T-SOD), manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione (GSH) and total antioxidant capacity (TAC). Adriamycin chemotherapy also decreased the expression of Bcl-2, increased the expression of iNOS and cell apoptosis in the liver and kidney. Multiple antioxidants ANTIOXIN had an antagonistic effect on these changes and significantly decreased the mortality of the experimental rats. These data demonstrated that adriamycin chemotherapy could cause oxidative stress to the whole body, on which multiple antioxidants based on the theory of 'multiple antioxidant chain' had effective protection.