Mangiferin as a Polyphenolic Scaffold for Enzyme Targeted Molecular Regulation of Carbohydrate Hydrolyzing Enzymes in...

Mangiferin, a bioactive xanthonoid predominantly present in mango, exhibits significant therapeutic potential in metabolic disorders, particularly diabetes mellitus. The present study was undertaken to compare the inhibitory potential of mangiferin with the standard drug acarbose against the carbohydrate hydrolyzing enzymes α-glucosidase and α-amylase using an integrated biochemical and in silico approach. Mangiferin was quantified in pulp and peel using LC-MS/MS analysis, revealing significant varietal variation, with Zardalu pulp (3.80 ± 0.2 mg/kg DW) and Dasheri peel (7.99 ± 0.2 mg/kg DW) showing the highest concentrations. Biochemical profiling demonstrated higher phenolic and flavonoid content in mango peels compared to pulp, indicating their potential as rich sources of bioactive compounds. Molecular docking analysis was performed using an AutoDock based workflow followed by residue-residue interaction analysis to evaluate ligand-protein interactions. Molecular docking analysis revealed strong binding affinity of mangiferin with α-glucosidase (-7.1 kcal/mol) and α-amylase (-8.4 kcal/mol), in comparison to standard drug acarbose. Interaction analysis showed stable hydrogen bonding, hydrophobic interactions and π-π stacking with key catalytic residues, suggesting effective inhibition of carbohydrate hydrolyzing enzymes. Structural validation using Ramachandran plot confirmed the reliability of protein models. These findings indicate that mangiferin exhibits a comparatively stronger binding affinity towards α-amylase than acarbose and may serve as a promising natural antidiabetic agent. The integration of biochemical and in silico findings highlights mango, as a promising source of natural antidiabetic compounds. However, further in vitro and in vivo studies are required to validate its therapeutic applicability.