Herb-drug interaction of Nisha Amalaki and Curcuminoids with metformin in normal and diabetic condition: A disease system approach

Nisha Amalaki (NA), formulation with Curcuma longa Linn (Turmeric, Haridra, Nisha in Sanskrit; Family: Zingiberaceae) and Phyllanthus emblica Linn (Indian gooseberry, Amlaki in Sanskrit; Family: Phyllanthaceae) which is described for various diseases including diabetes in ayurvedic texts and Nighantus. The aim of the present study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) interactions of chemically standardized NA and Curcuminoids (CE) with metformin (MET) in normal and diabetic animals. Oral administration of NA (200 mg/kg) and CE (30 mg/kg) was carried out for seven days followed by co-administration of MET till fifteen days. MET plasma PK parameters including C max, AUC 0-∞, t 1/2, CL and V d were measured on the eighth day. PD parameters including plasma glucose AUC followed by oral glucose tolerance test, high-density lipoproteins (HDL), total cholesterol (TC) and triglycerides (TG) were measured on the fifteenth day. In normal animals, co-administration of NA + MET and CE + MET resulted in significant increase (p < 0.05) in C max, AUC 0-∞, t 1/2, and reduction of CL and V d. We report that co-administration of NA + MET and CE + MET significantly (p < 0.01, p < 0.001) reduced plasma glucose level, HDL level while a notable reduction in TG and TC level was observed. Interestingly, in diabetic condition, co-administration of NA + MET and CE + MET indicated a significant decrease (p < 0.05) in C max, AUC 0-∞, t 1/2 and enhanced CL and V d. Hence, to conclude, co-administration of NA + MET and CE + MET resulted in beneficial PK and PD interactions leading to antihyperglycemic and antihyperlipidemic effects in both conditions. However, PK interaction was drastically different in diabetic and normal conditions.