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地黄(Gaertn.)多糖改善链脲佐菌素诱导的糖尿病小鼠的高血糖、高脂血症和血管炎症。

Rehmannia glutinosa (Gaertn.) DC. polysaccharide ameliorates hyperglycemia, hyperlipemia and vascular inflammation in streptozotocin-induced diabetic mice.

机构信息

Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, PR China.

Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, PR China.

出版信息

J Ethnopharmacol. 2015 Apr 22;164:229-38. doi: 10.1016/j.jep.2015.02.026. Epub 2015 Feb 17.

Abstract

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-α, 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.

摘要

ETHNOPHARMACOLOGICAL 相关性:地黄(Gaertn。)DC.(RG)已被广泛用作治疗糖尿病及其并发症的传统中药。RG 的多糖部分已被提出通过腹腔内给药具有降血糖作用,然而,RG 多糖(RGP)降血糖作用的机制仍知之甚少。在这里,我们研究了口服纯化 RGP 的抗高血糖和抗高血脂作用及其在链脲佐菌素(STZ)诱导的糖尿病小鼠中的潜在机制。

材料和方法

通过 GC 和 FT-IR 确定 RGP 的初步结构。用 STZ 注射小鼠诱导 1 型糖尿病。RGP 以 20、40 和 80 mg/kg/天的剂量口服给予小鼠 4 周,并用二甲双胍作为阳性对照。4 周后,测定血液生化参数、胰腺胰岛素含量、体外胰岛素分泌、肝糖原含量和磷酸烯醇丙酮酸羧激酶(PEPCK)的 mRNA 表达。

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 给药可显著降低糖尿病小鼠的血糖、总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平,升高高密度脂蛋白胆固醇和胰岛素水平,同时增加体重和胰腺胰岛素含量。体外研究表明,RGP 可显著增强糖尿病小鼠胰岛的基础和葡萄糖刺激的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减少。此外,RGP 表现出强大的抗炎和抗氧化活性,表现为糖尿病小鼠血液中 TNF-α、IL-6、单核细胞趋化蛋白-1、MDA 水平降低,SOD 和 GPx 活性升高。

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、高血脂、血管炎症和氧化应激,因此可能是 1 型糖尿病的潜在治疗选择。

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