Tannins from Phyllanthus niruri: α-glucosidase inhibition mechanism and molecular interaction analysis

Abstract

Hyperglycaemia, a frequent complication of diabetes mellitus, is often managed by inhibiting α-glucosidase, a key carbohydrate-hydrolysing enzyme. In this work, Phyllanthus niruri L., Phyllanthaceae, traditionally used for diabetes mellitus management, was investigated for its bioactive compounds and their α-glucosidase inhibitory potential. In vitro and in silico studies were conducted to evaluate the inhibitory activity of P. niruri fractions. Fraction 21, which exhibited potent α-glucosidase competitive inhibition (0.8742 µg ml−1), was analysed with LC-ESI-MS/MS, identifying six major compounds. Molecular docking and dynamics simulations revealed that corilagin, one of the identified bioactives, is a key inhibitor. The simulations indicated that α-glucosidase alternates between open and closed conformations, with corilagin binding strongly to the active site (including residue Tyr71) via its galloyl group specifically in the closed state. These findings are consistent with the traditional use of P. niruri for hyperglycaemia management, but do not constitute clinical validation. They also highlight its bioactive compounds, particularly corilagin, as promising therapeutic agents for the management of hyperglycaemia in diabetes mellitus.