Assessment of Pharmacodynamic and Pharmacokinetic Interaction of Aqueous Extract of Cassia auriculata L. and Metformin in Rats

Background: Cassia auriculata L. (CA) leaf extract might increase the body's production of insulin thereby suppressing the elevated blood glucose and lipid levels in diabetic rats. CA has been used as dietary supplement in India from ancient times. Objective: The present study was to elucidate the synergistic pharmacodynamic (PD) and pharmacokinetic (PK) interaction of metformin (MT) with CA. Materials and Methods:A simple, precise reverse phase high performance liquid chromatography - UV detection mode method was developed to quantify MT in rat plasma. In PD interaction, streptozotocin (45mg/kg, intraperitoneally) induced diabetic Wistar rats weighing 180–250 g of either sex were randomized to receive MT (90 mg/kg, MT-HD), CA (500 mg/kg) separately and in combination of MT (90 mg/kg, MT-HD) + CA (500 mg/kg), and MT (45 mg/kg, MT-LD) + CA (500 mg/kg) (all oral) along with normal and diabetic control groups for 21 days. PK of MT was carried out in normal rats with preadministration of CA (500 mg/kg) for 14 days. Results: PD data showed reasonable blood glucose lowering effect of CA. The reduction of MT dose with combination of CA achieved a similar blood glucose lowering effect of MT alone. PK data showed enhanced time taken to achieve maximum plasma concentration (C_max), area under the curve (AUC_0-t), and C_maxin combination group of MT (90mg/kg) and CA (500mg/kg), and reduction of MT dose in Group III had a reduced C_maxand AUC_0-tcompared to MT alone treated groups. Conclusion: Co-administration of CA with MT at varying dose showed a synergistic herb-drug interaction. Thus using the synergistic herb-drug interaction, the dose level of MT may be reduced to produce the same therapeutic effect as when taken alone.