Mode of action of three structurally different hypoglycemic agents: a comparative study.

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.

Mechanism of blood sugar lowering by a swerchirin-containing hexane fraction (SWI) of Swertia chirayita.

Mechanism of blood sugar lowering by the crude/impure swerchirin (SWI) isolated from the hexane fraction of Swertia chirayita was investigated. Single oral administration of SWI (50 mg/kg, body wt) to fed CF rats induced about 60% (max.) fall in blood glucose by 7 hr post-treatment. This was associated with marked depletion of aldehyde-fuchsin stained beta-granules and immunostained insulin in the pancreatic islets. In vitro, glucose uptake and glycogen synthesis by muscle (diaphragm) was significantly enhanced by the serum of SWI-treated rat. At 100, 10 and 1 microM final concentration, SWI greatly enhanced glucose (16.7 mM)-stimulated insulin release from isolated islets. It is therefore concluded that SWI lowers blood glucose level by stimulating insulin release from islets of Langerhans.

Swerchirin induced blood sugar lowering of streptozotocin treated hyperglycemic rats.

Effect of Swerchirin (1:8 dihydroxy 3:5 dimethoxy xanthone) isolated from hexane fraction of Swertia chirayita on the blood sugar level of healthy and streptozotocin treated rats was studied. Streptozotocin was administered in citrate buffer (pH-4.5) intravenously / 35 and 65 mg/kg body wt to Charles Foster strain albino rats. Swerchirin (50 mg/kg, po) suspended in gum acacia was fed through cannula to the above rats and to a group of healthy rats. Blood sugar estimated at 0, 1, 3 and 7 hr after, indicated a very significant lowering in healthy and streptozotocin (35 mg/kg iv) but not in streptozotocin (65 mg/kg) treated rats.