Rehmannia glutinosa (Gaertn.) DC. polysaccharide ameliorates hyperglycemia, hyperlipemia and vascular inflammation in streptozotocin-induced diabetic mice
Rehmannia glutinosa (Gaertn.) DC. polysaccharide ameliorates hyperglycemia, hyperlipemia and vascular inflammation in streptozotocin-induced diabetic mice
复制标题
地黄 (Gaertn.) DC。
DOI：
10.1016/j.jep.2015.02.026
复制
发表时间：
2015-04-22
影响因子：
5.4
通讯作者：
Huang, Kaixun
中科院分区：
文献类型：
--
作者：
Zhou, Jun;Xu, Gang;Huang, Kaixun
民族药理学相关性：地黄直流。作为治疗糖尿病及其并发症的中草药，RG已被广泛应用。RG多糖部分已被提出通过腹腔给药具有降糖作用，然而，RG多糖（RGP）降糖作用的机制尚不清楚。本实验研究了纯化RGP对链脲佐菌素（STZ）诱导的糖尿病小鼠的降糖和降血脂作用及其机制。材料与方法：采用气相色谱法和红外光谱法测定RGP的初步结构。小鼠注射STZ诱导1型糖尿病。以二甲双胍为阳性对照，口服剂量分别为20、40、80 mg/kg/d的RGP 4周。4周后测定各组大鼠血液生化指标、胰腺胰岛素含量、体外胰岛素分泌、肝糖原含量及磷酸烯醇丙酮酸羧化激酶mRNA表达量。结果：RGP由鼠李糖、阿拉伯糖、甘露糖、葡萄糖和半乳糖组成，摩尔比为1.00:1.26:0.73:16:45:30.40，平均分子量为63.5 kDa。RGP显著降低了糖尿病小鼠的血糖、总胆固醇、甘油三酯、低密度脂蛋白-胆固醇水平，并增加了高密度脂蛋白-胆固醇和胰岛素水平，同时增加了体重和胰腺胰岛素含量。体外研究表明，RGP可显著提高糖尿病小鼠基础胰岛素分泌和葡萄糖刺激胰岛素分泌，以及胰岛胰岛素含量。此外，RGP逆转了糖尿病小鼠肝脏中PEPCK mRNA表达的增加和糖原含量的降低。此外，RGP还具有较强的抗炎和抗氧化活性，可降低糖尿病小鼠血液中tnf - α、IL-6、单核细胞趋化蛋白-1、MDA的水平，并提高血液中SOD和GPx的活性。结论：综上所述，RGP可有效改善stz诱导的糖尿病小鼠的高血糖、高脂血症、血管炎症和氧化应激，可能是一种潜在的治疗1型糖尿病的选择。2015爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: Rehmannia glutinosa (Gaertn.) DC. (RG) has been widely used as traditional Chinese herbal medicine for treatment of diabetes and its complications. The polysaccharide fraction of RG has been proposed to possess hypoglycemic effect by intraperitoneal administration, however, the mechanisms responsible for the hypoglycemic effect of RG polysaccharide (RGP) remain poorly understood. Here we studied the anti-hyperglycemic and anti-hyperlipidemic effect of oral administration of a purified RGP and its underlying mechanisms in streptozotocin (STZ)-induced diabetic mice.Materials and methods: The preliminary structure of RGP was determined by GC and FT-IR. Mice were injected with STZ to induce type 1 diabetes. RGP at doses of 20, 40 and 80 mg/kg/day was orally administered to mice for 4 weeks, and metformin was used as positive control. After 4 weeks, the blood biochemical parameters, the pancreatic insulin contents, in vitro insulin secretion, the hepatic glycogen contents and mRNA expression of phosphoenolpyruvate carboxyl kinase (PEPCK) were assayed.Results: RGP was composed of rhamnose, arabinose, mannose, glucose and galactose in the molar ratio of 1.00:1.26:0.73:16.45:30.40 with the average molecular weight of 63.5 kDa. RGP administration significantly decreased the blood levels of glucose, total cholesterol, triglycerides, low density lipoprotein-cholesterol, and increased the blood levels of high density lipoprotein-cholesterol and insulin in diabetic mice, concurrent with increases in body weights and pancreatic insulin contents. The in vitro study revealed that RGP significantly enhanced both basal and glucose-stimulated insulin secretions, as well as islet insulin contents in the pancreatic islets of diabetic mice. Moreover, RGP reversed the increased mRNA expression of PEPCK and the reduced glycogen contents in the liver of diabetic mice. Furthermore, RGP exhibited potent anti-inflammatory and anti-oxidative activities, as evidenced by the decreased blood levels of TNF-alpha, IL-6, monocyte chemoattractant protein-1, MDA, and also the elevated blood levels of SOD and GPx activities in diabetic mice.Conclusions: Taken together, RGP can effectively ameliorate hyperglycemia, hyperlipemia, vascular inflammation and oxidative stress in STZ-induced diabetic mice, and thus may be a potential therapeutic option for type 1 diabetes. (C) 2015 Elsevier Ireland Ltd. All rights reserved.