Exploring the anti-diabetic potential of barnyard millet: insights from virtual screening, MD simulation and MM-PBSA

Barnyard millet (<i>Echinochloa frumentacea</i>) is a nutritionally superior grain and a rich source of dietary fiber, and protein. It helps in managing health and dietary issues such as malnutrition, diabetes, obesity, and celiac disease. Its low content of slowly digestible carbohydrates promotes a gradual release of glucose, helping to maintain stable blood glucose levels. The present study aims to identify and screen phytochemicals in the barnyard millet and explore its anti-diabetic activity through an <i>in-silico</i> study. Gas chromatography-mass spectrometry (GC-MS) analyses of the seed extract revealed the occurrence of 73 bioactive compounds that are known to possess a variety of pharmacological activities. Based on the virtual screening analysis, phytochemicals interacted with five different diabetic targets, with diosgenin demonstrating the lowest binding affinity across four receptors. Specifically, diosgenin showed a binding affinity of -9.2 kcal/mol with the Insulin receptor (PDB ID: 1IR3), -8.7 kcal/mol with Peroxisome proliferator-activated receptors (PDB ID: 3G9E), -7.5 kcal/mol with Tyrosine phosphatase 1-beta (2F70), and -6.5 kcal/mol with the Glucagon receptor (PDB ID: 5EE7). For Aldose reductase (PDB ID: 4XZH), Docosahexaenoic acid exhibited the lowest binding affinity of -9.9 kcal/mol. The dynamic behavior of 2F70-Diosgenin docked complexes throughout a 500 ns trajectory run was investigated further. The RMSD and RMSF analyses reveal that the complex remains structurally stable. The binding free energies were computed using the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) methodology. The calculation results show that the predicted free energies of the complex are stable. These results suggest that the 2F70-Diosgenin complex is stable, highlighting its potential for further wet lab validation.