Comparative study of antidiabetic potential of major phytochemicals in Sri Lankan Thebu (Costus speciosus): Computational insights

Abstract

In the 21st century's most rapidly expanding health concern worldwide is diabetes. Type 2 diabetes is a major public health concern and is more prevalent than Type 1. Costus speciosus (Thebu) has been known as the insulin plant containing several numbers of bioactive, phytoconstituents. This computational research study was focused on investigating the mechanistic activity of some antidiabetic compounds (Diosgenin, Costunolide & Eremanthin) available in Thebu. Molecular structures were screened from a PubChem database and corresponding protein crystal structures of Alphaamylase(4GQR), Alpha-glucosidase(2QMJ), Protein Tyrosine Phosphatase 1B(2QBP), and Inducible Nitric oxide synthase(4NOS) were retrieved from the protein data bank. The structures were optimized using the density functional theory method with B3LYP functional and 6-311G++ (d, p) basis set. The scoring function of Autodock 4.2.6 was used to determine the docked compounds' binding free energies and, for accurate results, six docking trials were carried out for each protein-ligand complex using the genetic algorithm. In this research, Acarbose and Lobeglitazone have been used as standard reference drugs for comparison with new ligand structures. The results of computational docking studies revealed these three ligands bound with all four proteins as providing binding energies, in the range between -6 to -11 kcal/mol while, diosgenin exhibited the lowest binding energies (more negative) with all four proteins as demonstrating the highest affinity with Alpha-amylase (-9.36 kcal/mol), Alpha-glucosidase (-9.79 kcal/mol), Tyrosine phosphatase 1B (-9.33 kcal/mol) and Inducible Nitric-oxide Synthase (- 10.43 kcal/mol). Further, the inhibition constant, Ki of diosgenin with four proteins revealed lower values as concluding that diosgenin has a greater inhibition of diabetic-related proteins. Eremanthin with Alpha-glucosidase, NOS also demonstrated a lower binding energy and a lower inhibition constant. A smaller inhibition constant relates to a stronger inhibitory potential, while lower binding energy values indicate a higher binding affinity of ligands with the proteins. These investigations positively supported the hypothesis that Costus speciosus might have an antidiabetic effect involved in the binding of these phytoconstituent ligands to their proteins. The affinity order of binding these phytochemicals into the four types of proteins exhibited as Costunolide < Eremanthin < Diosgenin. In conclusion, these computational insights encourage the design of structurally novel pharmaceuticals.