Piper betle L. is widely distributed and commonly used medicinally important herb. It can also be used as a medication for
type 2 diabetes patients. In this study, compounds of P. betle were screened to investigate the inhibitory action of
alpha-amylase and
alpha-glucosidase against
type 2 diabetes through molecular docking, molecular dynamics simulation, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. The molecule apigenin-7-O-glucoside showed the highest binding affinity among 123 (one hundred twenty-three) tested compounds. This compound simultaneously bound with the two-target
proteins alpha-amylase and
alpha-glucosidase, with high molecular mechanics-generalized born surface area (MM/GBSA) values (ΔG Bind = -45.02 kcal mol-1 for
alpha-amylase and -38.288 for
alpha-glucosidase) compared with control inhibitor
acarbose, which had binding affinities of -36.796 kcal mol-1 for
alpha-amylase and -29.622 kcal mol-1 for
alpha-glucosidase. The apigenin-7-O-glucoside was revealed to be the most stable molecule with the highest binding free energy through molecular dynamics simulation, indicating that it could compete with the inhibitors' native
ligand. Based on ADMET analysis, this
phytochemical exhibited a wide range of physicochemical, pharmacokinetic, and
drug-like qualities and had no significant side effects, making them prospective
drug candidates for
type 2 diabetes. Additional in vitro, in vivo, and clinical investigations are needed to determine the precise efficacy of drugs.