Department of Food and Nutrition, Sunchon National University, Suncheon 540-742, Republic of Korea.
Chem Biol Interact. 2010 Dec 5;188(3):635-42. doi: 10.1016/j.cbi.2010.09.019. Epub 2010 Sep 24.
The purpose of this study was to assess the effects of low-dose ursolic acid (UA) on glycemic regulation and immune responses in streptozotocin-nicotinamide (STZ/NA)-induced diabetic mice. Diabetic mice were supplemented with two different doses of UA (0.01 and 0.05%, w/w) or metformin (0.5%, w/w) for 4 weeks. Compared with the untreated diabetic group, UA and metformin significantly improved blood glucose, glycosylated hemoglobin, glucose tolerance, insulin tolerance and plasma leptin levels as well as aminotransferase activity. The plasma and pancreatic insulin concentrations were significantly higher in both UA groups than in the untreated diabetic group. Supplementation with metformin increased the pancreatic insulin level without a change in the plasma insulin level. The relative thymus weights were lower in the untreated diabetic group compared to the non-diabetic group; however, the UA or metformin group had significantly improved thymus weights. Mice receiving UA or metformin supplementation had increased CD4(+)CD8(+) subpopulations in the thymus compared to the untreated diabetic mice. Concanavalin A-stimulated splenic T-lymphocyte proliferation and single-positive (CD4(+) and CD8(+)) subpopulations were significantly higher in the UA-supplemented diabetic groups than in the untreated diabetic group, but lipopolysaccharide-stimulated B-lymphocyte proliferation and the CD19(+) subpopulation were not significantly different among the groups. In the STZ/NA-induced diabetic mice, metformin increased the splenic T-lymphocyte CD4(+) and CD8(+) cell numbers without any change in T-lymphocyte proliferation. Both doses of UA lowered splenic IL-6 levels, whereas metformin increased IFN-γ, IL-6 and TNF-α levels compared to the untreated diabetic mice. These results suggest that low-dose UA may be used as a hypoglycemic agent and immune modulator in non-obese type 2 diabetic mice.
本研究旨在评估低剂量熊果酸（UA）对链脲佐菌素-烟酰胺（STZ/NA）诱导的糖尿病小鼠血糖调节和免疫反应的影响。糖尿病小鼠分别补充两种不同剂量的 UA（0.01%和 0.05%，w/w）或二甲双胍（0.5%，w/w）4 周。与未治疗的糖尿病组相比，UA 和二甲双胍显著改善了血糖、糖化血红蛋白、葡萄糖耐量、胰岛素耐量和血浆瘦素水平以及氨基转移酶活性。与未治疗的糖尿病组相比，两组 UA 组的血浆和胰腺胰岛素浓度均显著升高。二甲双胍增加了胰腺胰岛素水平，而不改变血浆胰岛素水平。与非糖尿病组相比，未治疗的糖尿病组的胸腺相对重量较低；然而，UA 或二甲双胍组的胸腺重量显著改善。与未治疗的糖尿病组相比，接受 UA 或二甲双胍补充的小鼠的胸腺中 CD4+CD8+亚群增加。与未治疗的糖尿病组相比，UA 补充的糖尿病组的刀豆蛋白 A 刺激的脾 T 淋巴细胞增殖和单阳性（CD4+和 CD8+）亚群显著增加，但脂多糖刺激的 B 淋巴细胞增殖和 CD19+亚群在各组之间没有显著差异。在 STZ/NA 诱导的糖尿病小鼠中，二甲双胍增加了脾 T 淋巴细胞的 CD4+和 CD8+细胞数量，而 T 淋巴细胞增殖没有任何变化。两种剂量的 UA 均降低了脾 IL-6 水平，而二甲双胍与未治疗的糖尿病小鼠相比，增加了 IFN-γ、IL-6 和 TNF-α水平。这些结果表明，低剂量 UA 可作为非肥胖 2 型糖尿病小鼠的降血糖剂和免疫调节剂。
