In vitro and in silico inhibitory validation of Tapinanthus cordifolius leaf extract on alpha-glucosidase in the management of type 2 diabetes

The anti-diabetic properties of medicinal plants are becoming more widely recognized. To identify potential anti-diabetic agents for diabetes drug discovery, the current study used in vitro and in silico approaches to assess the alpha glucosidase inhibitory activities of Tapinanthus cordifolius (TC) leaf extracts and its bioactive components respectively. In vitro alpha glucosidase inhibitory assay was carried out on TC extract and fractions at various concentrations (50-1600 mu g/mL), and the compounds with alpha glucosidase inhibitory potentials were identified using molecular docking, pharmacophore modelling, and molecular dynamics simulation. The crude extract exhibited the highest activity with an IC50 value of 248 mu g/mL. Out of the 42 phytocompounds of the extract, alpha-Tocopherol-beta-D-mannoside gave the lowest binding energy of -6.20 Kcal/mol followed by, 5-Ergosterol (-5.46 kcal/mol), Acetosyringone (-4.76 kcal/mol), and Benzaldehyde, 4-(Ethylthio)-2,5-Dimethoxy-(-4.67 kcal/mol). The selected compounds interacted with critical active site amino acid residues of alpha-glucosidase, just like the reference ligand. Molecular dynamics simulation revealed the formation of a stable complex between a-glucosidase and alpha-Tocopherol-beta-D-mannoside, with ASP 564 sustaining two hydrogen bond connections for 99.9 and 75.0% of the simulation duration, respectively. Therefore, the selected TC compounds, especially alpha-Tocopherol-beta-D-mannoside might be explored for future research and development as diabetic medicines.

Automated summary

In this study, in vitro and in silico approaches were used to evaluate the alpha glucosidase inhibitory activities of Tapinanthus cordifolius leaf extracts and its bioactive components. The crude extract exhibited the highest activity with an IC50 value of 248μg/mL. Among the 42 phytocompounds tested, alpha-Tocopherol-beta-D-mannoside showed the greatest potential as an alpha glucosidase inhibitor with the lowest binding energy of -6.20 kcal/mol. These findings suggest that TC compounds, particularly alpha-Tocopherol-beta-D-mannoside, have potential for future research and development as diabetic medicines.