Impact of Fenugreek Oil on Sitagliptin's Pharmacokinetic and Pharmacodynamic Profile: A Computational Docking Study to Correlate Blood Glucose Level

Abstract

Sitagliptin, a DPP-4 inhibitor, performs by blocking the enzyme dipeptidyl peptidase-4 (DPP-4), which usually degrades incretin hormones that regulate blood glucose level. By inhibiting DPP-4, Sitagliptin enhances incretin levels, promoting insulin release and reducing liver glucose production. This study aimed to investigate the pharmacokinetic and pharmacodynamic interaction in between Sitagliptin, and fenugreek oil. The pharmacokinetic interactions were investigated with molecular docking studies and the results revealed that the absorption of Sitagliptin may be more in presence of fenugreek oil due to high binding energy of linoleic acid, linolenic acid and oleic acid present in fenugreek oil with PGlycoprotein (P-gp). The albumin binding capacity is less from the fatty acids of fenugreek oil compared to Sitagliptin. The metabolism of Sitagliptin caused by CYP3A4 is less in presence of fenugreek oil as the docking score is more with the components of fenugreek oil. This molecular docking study predicts an improvement of oral bioavailability of Sitagliptin in presence of fenugreek oil due to increased absorption and reduced metabolism. Pharmacodynamic studies were carried out by observing the blood glucose level in Streptozotacin induced diabetic rats. Higher percentage reduction in blood glucose was observed from the group treated with Sitagliptin and fenugreek oil compared to test group treated with Sitagliptin. Thus molecular docking studies are correlated with in-vivo experimental blood glucose data.