In situ net fishing of α-glucosidase inhibitors from evening primrose (Oenothera biennis) defatted seeds by combination of LC-MS/MS, molecular networking, affinity-based ultrafiltration, and molecular docking.

Abstract

Defatted seeds of evening primrose (DSEP), the by-product of evening primrose oil manufacture, exhibit potential α-glucosidase inhibitory activity; however, presently they are routinely discarded as waste. In this study, an in situ net fishing strategy was proposed for rapid recognition of α-glucosidase inhibitors from DSEP. Firstly, the DSEP extraction method was optimized employing a response surface methodology for the recovery of α-glucosidase inhibitors, just like "finding a good fishery before net fishing". Then, molecular networks of DSEP were generated by GNPS-based molecular networking after LC-MS/MS analysis, just like "casting tight nets in the fishery". Subsequently, affinity-based ultrafiltration was carried out for fishing the "hit" together with its structural analogues according to the molecular networks, just like "hauling the specific net fishing". Finally, molecular docking analysis was performed to rapidly verify α-glucosidase inhibitory activities of the potential bioactive components and predict their inhibition mechanisms. In the results, DSEP displayed significant inhibitory effects against yeast and rat intestinal α-glucosidase, and the results of an oral starch tolerance test suggested that DSEP showed postprandial blood-glucose-lowering activity. Moreover, 1-galloyl-glucose, gallic acid, methyl gallate, 1,6-digalloyl-β-D-glucose, and 1,3,6-trigalloylglucose were rapidly identified as potential α-glucosidase inhibitors present in DSEP.