Molecular Docking and Dynamics Simulation of Natural Compounds from Betel Leaves (Piper betle L.) for Investigating the Potential Inhibition of Alpha-Amylase and Alpha-Glucosidase of Type 2 Diabetes

Abstract

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.

Evaluation of Antidiabetic Effect of Luteolin in STZ Induced Diabetic Rats: Molecular Docking, Molecular Dynamics, In Vitro and In Vivo Studies

“…The Desmond tool, from Schrodinger, was used to run MD simulations to obtain an insight into the binding stabilization of the receptor α-glucosidase’s (PDB: 3W37) native structure and in docked complexes with LUT and acarbose. Before the MD simulations, the hydrogen bond network in both the native and docked complex structures were refined at pH, employing the Protein Preparation Wizard from Schrodinger, and the final restrained minimization was carried out using the OPLS3e force field [ 39 ]. An orthorhombic box, solvated with a TIP3P water model, 0.15 M NaCl counter ions, and a system builder module, were used to introduce more minimized structures into the workspace.…”

In Silico and In Vitro Analyses to Repurpose Quercetin as a Human Pancreatic α-Amylase Inhibitor

“…The compounds kaempferol, quercetin, scutellarin, and vitexin achieved stability within 10 ns, exhibiting average RMSDs of 0.263, 0.270, 0.254, and 0.26 nm, respectively (Table ). The acarbose–protein complex exhibited the highest level of stability, as evidenced by the RMSD value of 0.168 nm, also supported by prior studies . This finding implies that the protein experienced less deviation upon formation of the complex with acarbose.…”

“…The acarbose−protein complex exhibited the highest level of stability, as evidenced by the RMSD value of 0.168 nm, also supported by prior studies. 40 This finding implies that the protein experienced less deviation upon formation of the complex with acarbose. Except for protocatechuic acid, all other protein−ligand complexes showed stability under a 100 ns simulation.…”

Dietary phenolic compounds as promising therapeutic agents for diabetes and its complications: A comprehensive review

“…It showed an IC 50 value of 2.838 ± 0.014 μg/mL against enzyme α‐glucosidase (Zeng et al., 2016 ). The blood–brain barrier (BBB) test, the AMES test (presence of mutagenic chemicals), and hepatotoxicity, for testing of drugs and toxicity, all showed no positive results for apigenin derivatives; as a consequence, they might be employed in potential treatments for type 2 diabetes (Ahmed et al., 2022 ). According to these investigations, apigenin may have the ability to treat diabetes.…”