Singh Vineeta, Singh S P, Singh Manoj, Gupta Atul Kumar, Kumar Anil
Department of Molecular Biology and Genetic Engineering, College of Basic Sciences and Humanities, G. B. Pant University of Agriculture and Technology, Pantnagar, 263145, India.
Appl Biochem Biotechnol. 2015 Mar;175(5):2542-63. doi: 10.1007/s12010-014-1448-3. Epub 2014 Dec 24.
The present investigation was undertaken to analyze the ethanolic extracts of leaves of Cinnamomum tamala and Aloe vera for their anti-diabetic and insulinomimitic effect by determining the levels of blood sugar, glycosylated hemoglobin, and serum lipid profile (total cholesterol, triglycerides, high density lipoprotein (HDL), and low density lipoprotein (LDL)) after daily administration of each alone and in combined at 250 mg/kg in alloxan (ALX)-induced diabetic rats. Treatment of diabetic rats with the extracts restored the elevated biochemical parameters significantly. The anti-diabetic effect further potentiated the insulin signaling pathway by co-administration of both extracts. The molecular mechanisms of modulating gene expression and cellular signaling through the insulin receptor were also evaluated on specific targets of the insulin signaling pathway, including insulin receptor substrate (IRS), phosphatidylinositol 3-kinase (PI3-K), AKT, and the glucose transporter (GLUT4) on NIH/3T3 cell line by western blotting, ELISA, semiquantitative RT-PCR, and real-time PCR. The active principle of both extracts revealed insulin mimicking effect as indicated by increased expression of pIRS1 and pAKT in time-dependent manner. There was no significant difference in PI3-K content between unchallenged and challenged groups. Enhanced expression of GLUT-4 transcript further suggested that the Cinnamomum and Aloe phytochemicals could serve as a good adjuvant in the present armamentarium of anti-diabetic drugs by either mimicking or improving insulin action. This study reveals that ethanolic extracts of C. tamala and A. vera have potent therapeutic efficacy and prospect for the development of phytomedicine for diabetes mellitus.
本研究旨在通过测定四氧嘧啶(ALX)诱导的糖尿病大鼠每日单独及联合给予250mg/kg的锡兰肉桂叶和库拉索芦荟叶乙醇提取物后血糖、糖化血红蛋白和血清脂质谱(总胆固醇、甘油三酯、高密度脂蛋白(HDL)和低密度脂蛋白(LDL))水平,分析其抗糖尿病和胰岛素模拟作用。用提取物治疗糖尿病大鼠可显著恢复升高的生化参数。两种提取物联合给药进一步增强了抗糖尿病作用及胰岛素信号通路。还通过蛋白质印迹法、酶联免疫吸附测定、半定量逆转录聚合酶链反应和实时聚合酶链反应,在NIH/3T3细胞系上对胰岛素信号通路的特定靶点,包括胰岛素受体底物(IRS)、磷脂酰肌醇3激酶(PI3-K)、AKT和葡萄糖转运蛋白(GLUT4),评估了通过胰岛素受体调节基因表达和细胞信号传导的分子机制。两种提取物的活性成分均显示出胰岛素模拟作用,表现为pIRS1和pAKT表达随时间依赖性增加。未刺激组和刺激组之间PI3-K含量无显著差异。GLUT-4转录本表达增强进一步表明,锡兰肉桂和芦荟的植物化学物质可通过模拟或改善胰岛素作用,成为当前抗糖尿病药物中的良好佐剂。本研究表明,锡兰肉桂和库拉索芦荟的乙醇提取物具有强大的治疗效果,在开发糖尿病植物药方面具有前景。