Molecular docking and inhibition kinetics of α-glucosidase activity by labdane diterpenes isolated from tora seeds (Alpinia nigra B.L. Burtt.).

Abstract

Current approach against type 2 diabetes involves α-glucosidase inhibitors like acarbose associated with many side effects. Therefore, as an alternative to the existing drug, many natural products mainly from plant sources have been investigated which inhibit α-glucosidase. Here, we have selected medicinally important Alpinia nigra to explore its α-glucosidase inhibitory activity. Organic extracts of seeds and two purified natural diterpenes I: (E)-labda-8(17), 12-diene-15, 16-dial and II: (E)-8β, 17-epoxylabd-12-ene-15, 16-dial from A. nigra were investigated towards inhibition of α-glucosidase activity. Dose-dependent inhibition pattern were observed for seed extracts and both the compounds. Further, inhibition kinetics studies of the diterpenes indicated a non-competitive type of inhibition against α-glucosidase. Docking studies were carried out which revealed that both the diterpenes interacted within the active site of N-terminal and C-terminal domain of human maltase-glucoamylase enzyme, respectively. This is the first report of α-glucosidase inhibitory activity of these isolated diterpenes and their higher inhibitory potential than any terpenoids studied till date against α-glucosidase.