A strategy for screening of α-glucosidase inhibitors from Morus alba root bark based on the ligand fishing combined with high-performance liquid chromatography mass spectrometer and molecular docking

Abstract A new method based on ligand fishing combined with high-performance liquid chromatography quadrupole-time-of-flight mass spectrometer and molecular docking was established to screen α -glucosidase inhibitors from a traditional Chinese medicine Morus alba root bark. α -Glucosidase was immobilized on magnetic nanoparticles, used as a solid support to incubate with crude extract. After ligand fishing, the eluates were analyzed by high-performance liquid chromatography quadrupole-time-of-flight mass spectrometer, obtaining eleven ligands ( 1 – 4 , 6 – 12 ) eventually. In order to discriminate the non-specific binders and discover powerful enzyme inhibitors, molecular docking was further performed and three of the eleven ligands were optimized to be excellent α -glucosidase inhibitors by the confirmation of isolation and bioassay of individual compounds. These three ligands, sanggenons G ( 6 ), O ( 7 ) and sanggenol G ( 12 ) exhibited striking inhibitory activities with extremely low IC 50 values. The results suggest that established method will be applied to a wide range of target protein to screen potential bioactive constituents from herbal medicines.