Studies on inhibition of α-glucosidase using debittered formulation of Bacopa monnieri juice: Enzyme inhibition kinetics, interaction strategy, and molecular docking approach.

Bacopa monnieri juice (BMJ) is traditionally used, reported, and scientifically validated for memory enhancement. However, its efficacy against diabetes is less explored. The extreme bitterness of BMJ restricts its commercial applications. This study investigates the reduction of bitterness of BMJ followed by evaluation for its α-glucosidase inhibitory activity. Initially, debittering of 30 % (v/v) BMJ using ZnSO (15 mM) was optimized by time-intensity analysis and molecular docking of ZnSO as well as bacoside A3, the main active compound in BMJ, with TAS2R14 taste receptor. The study indicated 5 hydrogen bonds to be involved in binding with bacoside A3 with binding energy of -11.82 Kcal/mol, while hydrogen bond, salt bridges and metal complexes were involved in binding of ZnSO with binding energy of -6.65 Kcal/mol. Subsequently, BMJ, ZnSO and BMJ + ZnSO (debittered juice) were also found to be potent inhibitors of α-glucosidase in dose-dependent manner. These inhibitors showed parabolic mixed inhibition of α-glucosidase, altered the secondary structure, and quenching of fluorescence. In silico studies revealed hydrogen bonding and hydrophobic interactions between inhibitors and α-glucosidase with lowest binding energy of -15.53 and -7.54 Kcal/mol being recorded for bacoside A3 and ZnSO, respectively. Molecular docking of other bioactive compounds in BMJ such as apigenin, luteolin, quercetin and bacopasaponin C also showed lower binding energy than the standard drug, acarbose (-5.84). This study inferred the binding of bacoside A3 at the active site of α-glucosidase and of ZnSO with other sites on the protein. The study proposes a debittered BMJ formulation to control hyperglycemia.