201012-1335嗯嗯呃(8)

嗯嗯呃

- 8 - 中国科技论文在线as hepatoprotective inhibition of the production of nitric oxide and tumor necrosis factor-α in macrophages, inhibition of human low density lipoprotein oxidation [18], anti-obese [19], anti-inflammatory [20] and anticomplement activities [21]. Little is known about the role of trans-tiliroside on diabetes so far. In this study, the effects of trans-tiliroside from Potentilla chinesis in normal, alloxan-induced diabetic mice, and STZ-induced diabetic rats were evaluated. The most common substances inducing diabetes in experimental animals are alloxan and streptozocin (STZ). STZ is taken up by pancreatic β-cells via glucose transporter GLUT2. The main cause of STZ-induced β-cell death is alkylation of DNA by the nitrosourea moiety of this compound. The toxic action of alloxan on pancreatic β-cells involves several processes such as oxidation of essential –SH groups, inhibition of β-cell glucokinase, generation of free radicals and disturbances in-intracellular calcium homeostasis [22]. Due to differences in the mechanism of action of streptozocin and alloxan, we decided to evaluate the effects of the trans- tiliroside isolated from Potentilla chinesis in normal, alloxan-induced diabetic mice, and STZ-induced diabetic rats. The results indicate that compound possess significant anti-hyperglycemic activity. In alloxan-induced diabetic mice, every dose (1.6, 0.8 and 0.4 mg/kg) treatment of trans-tiliroside reduced the mean blood glucose level for 15 days. The anti-hyperglycemic activity of this compound was further confirmed in STZ-induced diabetic rats. Since diabetes is a chronic disease, a long-term therapy is required. Therefore, we administered the trans-tiliroside for 12 weeks in STZ-induced diabetic rats in order to demonstrate the anti-hyperglycemic effect. Our results proved a significant and sustained anti-hyperglycemic effect of trans-tiliroside (1.2 and 0.3 mg/kg) during 12 weeks of daily administration, compared with the diabetic control group. To the best of our knowledge, trans-tiliroside is the first flavonoid example of potent antidiabetic effects at low doses without toxic effects from natural products [16,23]. The continuous treatment with trans-tiliroside caused no significant effect in the normal treated rats. The above observations suggested that the continuous use of this compound or the accidental overdose will not result in hypoglycemic shock. In this way this compound will be better than insulin or sulfonylurea drugs, which causes severe hypoglycemia when taken in excessive doses [24].

Lipids play an important role in the pathogenesis of diabetes mellitus. The level of serum lipids is usually raised in diabetes and such an elevation represents a risk factor for coronary heart disease [25].Since diabetes is known to induce the rise in blood sugar was accompanied with marked increase in TC, LDL-C, TG and reduction in HDL-C in diabetic animals [26,27]. Therefore, the effects of trans-tiliroside isolated from Potentilla chinesis on the levels of lipid parameters in diabetic animals were also studied. In the present study, the rise in blood sugar was accompanied with marked increase in TC, LDL-C, TG and reduction in HDL-C in STZ-induced diabetic rats. The result of this study reveals that a regular administration of the trans-tiliroside in long-term treatment nearly normalized lipid profile in STZ-induced diabetic rats. The dose of 1.2 mg/kg not only lowered TC, TG and LDL but also enhanced the cardioprotective lipid HDL-C [28].

Since diabetes mellitus is considered as a free radical-mediated disease, increased free radical production as well as reduced antioxidant defense responses may give rise to increased oxidative stress in diabetic condition [29,30]. The elevated levels of blood glucose in diabetes are associated with increased lipid peroxidation, which may contribute to long-term tissue damage [31]. Lipid peroxidation is a free radical-mediated propagation of oxidative insult to polyunsaturated fatty acids, and is increased in diabetic rats as evident from elevation of lipid peroxidation product MDA in serum. Reduced activities of SOD and increased MDA levels in tissues have been observed during diabetes and this may result in a number of deleterious effects due to the accumulation of superoxide radicals (O 2•) [32,33]. The in vitro antioxidant activity (DPPH radical