Molecular Docking and In Vitro Assessment of <i>Gymnema sylvestre</i> R. Br. and <i>Trigonella foenum‐graecum</i> L. Phytochemicals as Dual α‐Amylase and α‐Glucosidase Inhibitors

Gymnema sylvestre R. Br. (gurmar, Asclepiadaceae) and Trigonella foenum-graecum L. (Fenugreek, Fabaceae) are medicinal plants with proven antidiabetic activity. This study employed the construction of a 221-compound library from G. sylvestre and T. foenum-graecum for virtual screening against α-amylase and α-glucosidase target proteins. It aimed to analyze phytochemical-target protein interactions via molecular dynamic simulations and validation of findings using in vitro antidiabetic assays. Bioinformatics tools facilitated virtual screening, molecular dynamics simulations, and ADMETox analysis. The α-amylase and α-glucosidase inhibitory potentials were screened in vitro using 50% EtOH extracts of G. sylvestre leaves and T. foenum-graecum seeds with acarbose as the reference compound. Trigoneoside XIIa (-9.1 kcal/mol) and trigofoenoside G (-9.8 kcal/mol) derived from T. foenum-graecum and gymnemasaponin V (-9.7 kcal/mol) derived from G. sylvestre showed the most stable binding interaction with the target proteins. In vitro assays further revealed that T. foenum-graecum seed extract showed the highest α-amylase inhibition (IC₅₀ = 12.09 ± 2.13 mg/mL) and α-glucosidase inhibition (IC₅₀ = 5.23 ± 0.33 mg/mL). Trigoneoside XIIa, trigofoenoside G, and gymnemasaponin V were identified as promising drug candidates for the development of antidiabetic drug leads, further validating the in vitro α-amylase and α-glucosidase inhibitory potentials.