Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
J Ethnopharmacol. 2011 Jan 27;133(2):598-607. doi: 10.1016/j.jep.2010.10.046. Epub 2010 Oct 28.
This study aims to investigate the hypoglycemic properties of Vernonia amygdalina Del. (VA) and its possible mechanisms of action in a single-dose STZ induced diabetic rat model.
A dose-response study was conducted to determine optimum dose for the hypoglycemic effect of VA in STZ-induced diabetic rats. The optimum dose (400 mg/kg) was used throughout the 28-day chronic study. Body weight, food and water intakes of the rats were monitored daily. Fasting blood serum, pancreas, liver and soleus muscle were collected for biochemical analyses. Chemical composition of VA was analysed using HPLC and LC-ESI-MS.
The study reveals that ethanolic extract of VA contains high level of polyphenols mainly 1,5-dicaffeoyl-quinic acid, dicaffeoyl-quinic acid, chlorogenic acid and luteolin-7-O-glucoside. In an oral glucose tolerance test, 400 mg/kg VA exhibited a significant improvement in glucose tolerance of the STZ-induced diabetic rats. 28-day treatment with 400 mg/kg VA resulted in 32.1% decrease in fasting blood glucose compared to diabetic control. VA also caused significant decrease (18.2% and 41%) in triglyceride and total cholesterol level. Besides, VA showed protective effect over pancreatic β-cells against STZ-induced damage, causing a slight increase in insulin level compared to diabetic control. VA administration also showed positive regulation of the antioxidant system, both enzymatic and non-enzymatic. Furthermore, VA was found to increase expression of GLUT 4 (24%) in rat skeletal muscle. Further tissue fractionation revealed that it can increase the GLUT 4 translocation (35.7%) to plasma membrane as well, suggesting that VA may stimulate skeletal muscle's glucose uptake. This observation is in line with the restoration in skeletal muscle glycogenesis of VA-treated group. However, no alteration was observed in GLUT 1 expression. In addition, VA also suppressed (40% inhibition) one of the key hepatic gluconeogenic enzymes, glucose-6-phosphatase (G6Pase).
VA possesses antihyperglycemic effect, most probably through increasing GLUT 4 translocation and inhibiting hepatic G6Pase. The polyphenols in the extract may be the candidates that are responsible for the above-mentioned biological activities.
本研究旨在探讨苦叶李（VA）的降血糖特性及其在链脲佐菌素（STZ）诱导的糖尿病大鼠模型中单剂量给药的可能作用机制。
进行剂量反应研究以确定 VA 在 STZ 诱导的糖尿病大鼠中降血糖作用的最佳剂量。在 28 天的慢性研究中使用最佳剂量（400mg/kg）。每天监测大鼠的体重、食物和水摄入量。采集空腹血清、胰腺、肝脏和比目鱼肌进行生化分析。使用 HPLC 和 LC-ESI-MS 分析 VA 的化学成分。
研究表明，VA 的乙醇提取物含有高水平的多酚，主要为 1,5-二咖啡酰奎宁酸、二咖啡酰奎宁酸、绿原酸和木犀草素-7-O-葡萄糖苷。在口服葡萄糖耐量试验中，400mg/kg VA 显著改善了 STZ 诱导的糖尿病大鼠的葡萄糖耐量。28 天用 400mg/kg VA 治疗可使空腹血糖降低 32.1%，与糖尿病对照组相比。VA 还可显著降低（18.2%和 41%）甘油三酯和总胆固醇水平。此外，VA 对 STZ 诱导的胰岛β细胞损伤具有保护作用，与糖尿病对照组相比，胰岛素水平略有升高。VA 给药还对抗氧化系统产生积极调节作用，包括酶促和非酶促作用。此外，发现 VA 可增加大鼠骨骼肌中 GLUT 4（24%）的表达。进一步的组织分离显示，它还可以增加 GLUT 4 的易位（35.7%）到质膜，表明 VA 可能刺激骨骼肌的葡萄糖摄取。这一观察结果与 VA 处理组骨骼肌糖生成的恢复一致。然而，GLUT 1 的表达没有改变。此外，VA 还抑制（40%抑制）一种关键的肝糖异生酶葡萄糖-6-磷酸酶（G6Pase）。
VA 具有降血糖作用，可能是通过增加 GLUT 4 易位和抑制肝 G6Pase 实现的。提取物中的多酚可能是负责上述生物活性的候选物质。
