Sapium ellipticum (Hochst) Pax ethanol leaf extract modulates glucokinase and glucose-6-phosphatase activities in streptozotocin induced diabetic rats

摘要

Objective: To examine the effects of Sapium ellipticum (SE) leaf extract on the hepatic activities of glucokinase and glucose-6-phosphatase in streptozotocin-induced diabetic Wistar rats. Methods: STZ-induced diabetic Wistar rats (four groups, n=8) were used in this study. SE was assessed at two different doses, 400 and 800 mg/kg BW, in comparison with metformin (METF) (12 mg/kg BW) as a reference antidiabetic drug. All treatments were done orally (p.o), twice daily at 8 h interval for a period of 21 days. Glucokinase and glucose-6-phosphatase activities were respectively determined using standard protocols. Hepatic and muscle glycogen contents were estimated as well. Results: STZ caused significant decrease in glucose-6-phosphatase activity and concomi-tant increase in glucokinase activity. SE extract especially at 400 mg dosage significantly reversed the alterations by increasing glucokinase activity by 40.31%and inhibiting glucose-6-phosphatase activity by 37.29%compared to diabetic control animals. However, the ef-fects were significantly lower than that of METF which enhanced glucokinase activity by 94.76%and simultaneously inhibited glucose-6-phosphatase activity by 49.15%. The extract also improved hepatic glycogen level by 32.37 and 27.06% at 400 and 800 mg dosage respectively. HPLC-MS analysis of some SE fractions in dynamic MRM mode (using the optimized compound-specific parameters) revealed among other active compounds, the presence of amentoflavone, which has been associated with antidiabetic function. Conclusions: The ability of SE extract to concurrently inhibit glucose-6-phosphatase and activate glucokinase in this study suggests that it may be a treatment option for type 2 diabetes patients, and the presence of amentoflavone in the plant extract may account for its anti-diabetic potential.