Characterization, inhibitory activity and mechanism of polyphenols from faba bean (gallic-acid and catechin) on α-glucosidase: insights from molecular docking and simulation study

The chemo-profiling of ethanolic extract of faba beans seeds was performed and explored as an α-glucosidase inhibitor. The inhibition of α-glucosidase is one of the alternatives approach to control postprandial hyperglycemia by, resulting in the delay of the carbohydrate digestion of absorbable monosaccharides. Ethanolic seed extract showed phenolic compounds, flavonoid such as gallic acid (m/z [M- H] = 169.0124,C₇H₆O₅) ellagic acid derivatives epigallocatechin (m/z [M- H = 305.0644,C₁₅H₁₄O₇),catechin (m/z [M- H] = 289.0656,C₁₅H₁₄O₆), epigallocatechin gallate (m/z [M- H] = 457.0578,C₂₂H₁₈O₁₁) and epicatechin monogallate (m/z [M- H] = 441.081, C₂₂H₁₈O₁₀). The extract was found to exert inhibitory activity (88.28 ± 2.67%) (IC₅₀ value of 2.30 ± 0.032 mg/mL) with a mixed mode of inhibition (Km, apparent = 0.54 ± 0.020 mM and Vmax, apparent 0.136 ± 0.04 mM/min). Molecular docking studies of gallic acid and catechin on α-glucosidase proposed productive binding modes having binding energy (-6.58 kcal/mol and -7.25 kcal/mol) with an effective number of hydrogen bonds and binding energy. Tyr63, Arg197, Asp198, Glu 233, Asn324, Asp 326 of α-glucosidase participated in binding events with gallic acid and catechin. Molecular dynamics simulation studies were performed for both complexes i.e. gal:α-glucosidase and cat:α-glucosidase along with apo state of α-glucosidase, which revealed stable systems during the simulation. These findings of the present study may give an insight into the further development of the novel antidiabetic drug from the seeds of faba beans.