College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Lvshunkou District, Dalian, Liaoning Province, 116044, China.
Phytother Res. 2015 Feb;29(2):228-40. doi: 10.1002/ptr.5243. Epub 2014 Oct 16.
The aim of the present paper was to investigate the effects and possible mechanisms of the total saponins from Dioscorea nipponica Makino (TSDN) against type 2 diabetes mellitus. Streptozotocin (STZ) with high-fat diet induced type 2 diabetes mellitus (T2DM) rats were treated with TSDN. Some biochemical parameters, target proteins and genes were investigated. The results showed that TSDN decreased the levels of food/water intake, fasting blood glucose and serum lipid parameters, ameliorated oral glucose and insulin tolerance test levels, markedly increased body weight and serum insulin, reduced excess free radicals and affected ossification and renal protection. Histopathological examination indicated that TSDN increased liver glycogen, decreased the production of lipid vacuoles and lightened liver damage. Further investigation showed that TSDN down-regulated the protein expressions of NF-κB, GRP78, ATF6, eIF2 and the levels of MAPK phosphorylation and up-regulated the protein expressions of IRS-1, GLUT-4, p-Akt and p-AMPK. In addition, TSDN obviously decreased the gene expressions of TNF-a, IL-6, PEPCK, G6Pase, GSK-3β and GSK-3β activity, and increased the gene expressions of PFK, PK and GK activity. These findings show the anti-diabetic activity of total saponins from D. nipponica Makino, which should be developed as a new potent drug for treatment of diabetes mellitus in future.
本文旨在研究穿山龙总皂苷（TSDN）对 2 型糖尿病的作用及可能机制。采用链脲佐菌素（STZ）联合高脂饮食诱导 2 型糖尿病（T2DM）大鼠，给予 TSDN 治疗。检测了一些生化参数、靶蛋白和基因。结果表明，TSDN 降低了摄食/饮水、空腹血糖和血清脂质参数水平，改善了口服葡萄糖和胰岛素耐量试验水平，显著增加了体重和血清胰岛素，减少了过多的自由基，并影响了骨化和肾脏保护。组织病理学检查表明，TSDN 增加了肝糖原，减少了脂质空泡的产生，减轻了肝损伤。进一步研究表明，TSDN 下调了 NF-κB、GRP78、ATF6、eIF2 的蛋白表达水平和 MAPK 磷酸化水平，并上调了 IRS-1、GLUT-4、p-Akt 和 p-AMPK 的蛋白表达水平。此外，TSDN 明显降低了 TNF-α、IL-6、PEPCK、G6Pase、GSK-3β和 GSK-3β 活性的基因表达，同时增加了 PFK、PK 和 GK 活性的基因表达。这些发现表明穿山龙总皂苷具有抗糖尿病活性，将来可能开发为治疗糖尿病的新型有效药物。
