Identification of PTP1B and alpha-Glucosidase Inhibitory Serrulatanes from Eremophila spp. by Combined use of Dual High-Resolution PTP1B and alpha-Glucosidase Inhibition Profiling and HPLC-HRMS-SPE-NMR

摘要

According to the International Diabetes Federation, type 2 diabetes (T2D) has reached epidemic proportions, affecting more than 382 million people worldwide. Inhibition of protein tyrosine phosphatase-1B (PTP1B) and a-glucosidase is a recognized therapeutic approach for management of T2D and its associated complications. The lack of clinical drugs targeting PTP1B and side effects of the existing a-glucosidase drugs, emphasize the need for new drug leads for these T2D targets. In the present work, dual high resolution PTP1B and a-glucosidase inhibition profiles of Eremophila gibbosa, E. glabra, and E. aff. drummondii "Kalgoorlie" were used for pinpointing a-glucosidase and/or PTP1B inhibitory constituents directly from the crude extracts. A subsequent targeted high-performance liquid chromatography high-resolution mass spectrometry solid-phase extraction nuclear magnetic resonance spectroscopy (HPLC-HRMS-SPE-NMR) analysis and preparative-scale HPLC isolation led to identification of 21 metabolites from the three species, of which 16 were serrulatane-type diterpenoids (12 new) associated with either a-glucosidase and/or PTP1B inhibition. This is the first report of serrulatane-type diterpenoids as potential a-glucosidase and/or PTP1B inhibitors.