Molecular Docking Evaluation of Flavonoids from Fenugreek (Trigonellafoenum-graecum) as Potential DPP-4 Inhibitors for Antidiabetic Activity

Type 2 Diabetes Mellitus is an extensive metabolic disorder, and dipeptidyl peptidase-4 is an important target for therapeutic strategies (World Health Organization, 2021). This study uses in silico molecular docking to examine the potential of four flavonoids from Trigonella foenum-graecum (fenugreek) seeds: rutin, quercetin, vitexin, and isovitexin, as natural dipeptidyl peptidase-4 (DPP-4) inhibitors for antidiabetic action. AutoDock Vina was used to dock the chosen ligands with the DPP-4 enzyme (PDB ID: 2OQV) while minimizing their energy. The binding interactions were then examined. At important catalytic residues, rutin showed significant hydrogen bonding and hydrophobic interactions, outperforming the co-crystallized inhibitor with the greatest binding affinity (−9.4 kcal/mol). Rutin's molecular complementarity was found to be favorable when the interaction profiles and binding orientations were examined using Discovery Studio Visualizer. According to the study, rutin's better binding affinity and interaction network suggest that it may have natural DPP-4 inhibitory properties. These findings offer valuable insights into fenugreek’s antidiabetic efficacy and support its traditional usage, suggesting further experimental validation of rutin for drug development.