Dipeptidyl peptidase-4 (DPP4) is an enzyme responsible for degrading incretin hormones, which are key regulators of insulin secretion and blood glucose levels. Inhibition of DPP4 prolongs incretin activity, thereby enhancing glycemic control and offering therapeutic benefits in the management of Type 2 diabetes mellitus (T2DM). Although synthetic DPP4 inhibitors are commonly used, plant-based compounds present a promising and potentially safer alternative. This study aimed to evaluate the DPP4 inhibitory potential of plant-derived compounds through in silico approaches, including molecular docking, molecular dynamics (MD) simulations, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. Among the screened compounds, Apigenin 7-O-methylglucuronide, a bioactive molecule, exhibited a higher binding affinity to DPP4 (-9.1 kcal/mol) compared to sitagliptin (-8.43 kcal/mol), a standard DPP4 inhibitor. Furthermore, MD simulations over 100 ns demonstrated greater stability of the Apigenin 7-O-methylglucuronide–DPP4 complex relative to the sitagliptin–DPP4 complex. ADMET profiling revealed favorable pharmacokinetic properties, including high oral bioavailability and minimal inhibition of cytochrome P450 enzymes. These findings underscore the potential of Apigenin 7-O-methylglucuronide as a natural DPP4 inhibitor and support its further investigation as a candidate for alternative T2DM therapies.
Dipeptidyl peptidase-4 inhibitor, apigenin 7-O-methylglucuronide, molecular docking, molecular dynamics simulation, type 2 diabetes
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