Saxena A M, Murthy P S, Mukherjee S K
Central Drug Research Institute, Lucknow, India.
Indian J Exp Biol. 1996 Apr;34(4):351-5.
The mechanism of dose-dependent hypoglycemic effect, the margin of safety and ED50 of three structurally unrelated compounds, tolbutamide (TB), centpiperalone (CP) and a swerchirin-containing fraction (SWI) from the plant Swertia chirayita, were investigated in experimental models. After a single oral administration of TB, CP and SWI to groups of normal and streptozotocin (STZ)-induced mild and severe diabetic rats, the blood sugar lowering effect and ED50 of the agents were determined. Plasma Immuno Reactive Insulin (IRI) levels and the degree of islet beta cell degranulation were assayed using RIA and histochemical staining, respectively, in normal rats treated with the agents. The percent blood sugar lowering, increase in IRI levels and beta cell degranulation were highest in CP treated normal rats (69, 124 and 75%, respectively). In addition, CP was the only agent found active in STZ-induced severely diabetic rats (P < 0.01). In STZ-mild diabetic rats, however, TB was more effective than CP and SWI. By analysis of data using Anova method, it is concluded that CP is more effective than SWI (P < 0.01) and TB. However, SWI an impure natural product showed better blood sugar lowering than tolbutamide which is a drug in use.
在实验模型中研究了三种结构不相关的化合物甲苯磺丁脲（TB）、百哌酮（CP）和来自植物印度獐牙菜的含獐牙菜苦素馏分（SWI）的剂量依赖性降血糖作用机制、安全范围和半数有效剂量（ED50）。将TB、CP和SWI分别单次口服给予正常组、链脲佐菌素（STZ）诱导的轻度和重度糖尿病大鼠组后，测定这些药物的降血糖作用和ED50。分别用放射免疫分析（RIA）和组织化学染色法检测这些药物处理的正常大鼠的血浆免疫反应性胰岛素（IRI）水平和胰岛β细胞脱颗粒程度。CP处理的正常大鼠的血糖降低百分比、IRI水平升高和β细胞脱颗粒程度最高（分别为69%、124%和75%）。此外，CP是唯一在STZ诱导的重度糖尿病大鼠中发现有活性的药物（P<0.01）。然而，在STZ诱导的轻度糖尿病大鼠中，TB比CP和SWI更有效。通过方差分析方法分析数据得出结论，CP比SWI（P<0.01）和TB更有效。然而，SWI这种不纯的天然产物的降血糖效果比正在使用的药物甲苯磺丁脲更好。
