Natural α-glucosidase inhibitors from selected medicinal plants in Malaysia

The most prevalent subtype of diabetes is Type 2 Diabetes Mellitus which results from an abnormal postprandial increase in blood glucose. Inhibition of the carbohydrate-hydrolysing enzymes (alpha-glucosidase and alpha-amylase) in the human digestive organs can control blood glucose levels, making it an important strategy in the management of Type 2 Diabetes Mellitus. A majority of the oral synthetic drugs which have been developed to treat Type 2 Diabetes Mellitus are expensive and have undesirable side effects. As a result, plant-derived remedies have become preferred alternatives as they are easily available, affordable and less harmful. Angustine (1) the major constituent in Nauclea subdita (Korth.) Steud., and (E)-labda-8(17),12-dien-15,16-dial (2) and zerumin A (3) of Alpinia pahangensis Ridley were evaluated for their α-glucosidase inhibitory activity. (E)-Labda-8(17),12-dien-15,16-dial (2) (IC50 = 39.7 μM) was identified as the most potent inhibitor among all three, followed by angustine (1) (IC50 = 48.1 μM) and zerumin A (3) (IC50 = 53.3 μM). Enzyme kinetic studies indicated that angustine (1) was a mixed-type inhibitor, while (E)-labda-8(17),12-dien-15,16-dial (2), and zerumin A (3) were non-competitive inhibitors. Molecular docking and molecular dynamics (MD) simulation studies were performed to predict the key interactions between the ligands and the target protein, 1AGM (complex of acarbose with glucoamylase from Aspergillus awamori). The results of the study of binding interaction energy suggested that angustine (1) has the potential to be used as a natural drug lead in the treatment of type 2 diabetes mellitus.