Exploring the Multi-targeted Therapeutic Mechanism of Bioactives from Glycine max in Treatment of type 2 Diabetes Mellitus and Obesity through an In-vitro and In-silico Approach

ABSTRACT: Type 2 Diabetes Mellitus is significantly affected by gluconeogenesis mediated glucose production. Various enzymatic targets and receptors are responsible in pathogenesis of diabetes and obesity. Despite many drugs are available to treat this condition but there is need to explore various natural bioactive molecules with appropriate potency and safety. The present investigation focuses on the multi-targeted activity of bioactive phytoconstituents of Glycine max (soybean) using computational approach. All the phytoconstituents were screened for drug-likeness and ADMET properties, among which 26 were considered for further studies. The binding affinity and interaction patterns within the active site of the enzymes was assessed with molecular docking study. Four key hydrogen bonds were identified between phytochemicals and allosteric amino acid residues through docking analysis. The hydrogen bonds included LYSB542 at 2.08 Å, ARG527 at 2.43 Å, GLU551 at 2.54 Å, and LYSD542 at 3.28 Å. Besides, the interactions were found hydrophobic in nature. This may inhibit the enzymes and stabilize it at the active binding pocket. The superior binding affinity of Genistein, Taraxerol, and β-Amyrin against the reference compounds make it very promising. Therefore, this indicates that it is a useful drug for T2DM and obesity management. Genistein was tested for in-vitro enzyme assay and exhibited comparable enzyme inhibition with standard acarbose. Computational studies shows that phytochemicals like Genistein derived from Glycine max are useful in the management of T2DM and found to be safe through in-silico studies. However, further experimental validation is needed to determine the safety and efficacy. Glycine max may provide potential therapeutic compounds for treatment of obesity and diabetes.