In silico docking and ADMET studies on clinical targets for type 2 diabetes correlated to in vitro inhibition of pancreatic alpha-amylase and alpha-glucosidase by rutin, caffeic acid, p-coumaric acid, and vanillin.

Abstract

Inhibition of pancreatic alpha-amylase and alpha-glucosidase is a common strategy to manage type 2 diabetes. This study focuses on the ability of compounds present in commercially available herbs and spices to inhibit pancreatic alpha-amylase and alpha-glucosidase. In silico molecular docking was performed to evaluate the binding affinity of the compounds present in herbs and spices. Molecular dynamics was performed with acarbose and rutin which had the best docking scores for pancreatic alpha-amylase and alpha-glucosidase. Six compounds (rutin, caffeic acid, p-coumaric acid, vanillin, ethyl gallate, and oxalic acid) with a range of docking scores were subjected to in vitro enzyme kinetic studies using pancreatic alpha-amylase and alpha-glucosidase biochemical assays. Acarbose, a prescribed alpha-amylase and alpha-glucosidase inhibitor, was used as a positive control. Ligands that interacted strongly with the amino acids at a particular site, were conformationally stable and had good docking scores. There was a correlation between the in silico and in vitro binding affinity. Caffeic acid, vanillin, ethyl gallate, and p-coumaric acid had inhibition constant (K_i) values that were not significantly different (p > 0.05) from the K_i of acarbose for pancreatic alpha-amylase. Rutin, caffeic acid, vanillin, and p-coumaric acid had K_i values that were not significantly different (p ˃ 0.05) from the K_i of acarbose for alpha-glucosidase. The cell viability of these compounds was assessed with the sulforhodamine B (SRB) assay in Caco2 cells. Caffeic acid, p-coumaric acid, rutin, and vanillin had Caco2 IC₅₀ values that were not significantly different (p ˃ 0.05) from that of acarbose. The evaluated compounds present in herbs and spices can potentially reduce hyperglycemia associated with type 2 diabetes. Herbs and spices with high levels of these compounds were identified and these were common verbena, sweet basil, tarragon, pepper, parsley, sorrel, and vanilla. These herbs and spices may reduce the required dose of prescription drugs, such as acarbose, thereby reducing costs and drug-associated side effects.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00324-6.