title: Assessment of Pharmacodynamic and Pharmacokinetic Interaction of Aqueous Extract of Cassia auriculata L. and Metformin in Rats.
abstract: 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.
  
  
  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 (Cmax), area under the curve (AUC0-t), and Cmax in combination group of MT (90mg/kg) and CA (500mg/kg), and reduction of MT dose in Group III had a reduced Cmax and AUC0-t compared to MT alone treated groups.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  Elucidating the synergistic pharmacodynamic (PD) and pharmacokinetic (PK) interaction of metformin (MT) with Cassia auriculata L. (CA)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 alonePK data showed enhanced time taken to achieve maximum plasma concentration (Cmax), area under the curve (AUC0-t), and Cmax in combination group of MT and CA, and reduction of MT dose had a reduced Cmax and AUC0-t compared to MT alone treated groupsCo-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. Abbreviations used: CA: Cassia auriculata L., PD: Pharmacodynamic, PK: Pharmacokinetic, MT: Metformin, RP-HPLC-UV: Reverse phase High Performance Liquid Chromatography-UV detection mode, Tmax: Time taken to achieve maximum plasma concentration, AUC0-t: Area under the curve, Cmax: Maximum plasma concentration.
authors.affiliation: Department of Pharmaceutical Chemistry, JSS College of Pharmacy (Affiliated to JSS University, Mysore), Ootacamund, The Nilgiris, Tamil Nadu, India.
authors.forename: Hemnath
authors.initials: H
authors.lastname: Elango
authors.affiliation: Department of Pharmacy Practice, JSS College of Pharmacy (Affiliated to JSS University, Mysore), Ootacamund, The Nilgiris, Tamil Nadu, India.
authors.forename: Sivasankaran
authors.initials: S
authors.lastname: Ponnusankar
authors.affiliation: Department of Pharmaceutical Chemistry, JSS College of Pharmacy (Affiliated to JSS University, Mysore), Ootacamund, The Nilgiris, Tamil Nadu, India.
authors.forename: Sankar
authors.initials: S
authors.lastname: Sundaram
keywords: Cassia auriculata L.; diabetes mellitus; herb-drug interactions; metformin; pharmacodynamic; pharmacokinetics