Diverse gallotannins with α-glucosidase and α-amylase inhibitory activity from the roots of Euphorbia fischeriana steud.

Abstract

A phytochemical investigation of the roots of Euphorbia fischeriana Steud. led to the isolation of eleven undescribed gallotannins, fishertannins A–K, together with four known analogues. Their structures were elucidated by the comprehensive spectroscopic data including UV, IR, HR-ESI-MS, and NMR, while the absolute configurations of the sugar moiety were determined by the acid hydrolysis and HPLC analyses. Fishertannin A possessed an unusual skeleton comprised of acetophenone, galloyl group, arabinofuranosyl and glucopyranosyl moieties. Fishertannin B, fishertannin H, fishertannin K, 1,2,3-tri-O-galloyl-β-D-glucopyranose, 3,4,6-tri-O-galloyl-D-glucopyranose, and 1,6-di-O-galloyl-β-D-glucopyranose displayed the potent α-glucosidase inhibitory activities with the IC50 values of 15.48–177.13 μM. Examination of the structure-activity relationships (SAR) demonstrated that the galloyl and glucopyranosyl moieties played a key role in the inhibitory activity for both α-glucosidase and α-amylase inhibitory activity. Among all isolates, 1,2,3-tri-O-galloyl-β-D-glucopyranose showed the most potent and highly specific inhibitory activity against α-glucosidase with an IC50 value of 15.48 ± 0.60 μM. The kinetic analysis of 1,2,3-tri-O-galloyl-β-D-glucopyranose disclosed the mixed inhibition type on α-glucosidase, and the molecular docking visualized the stable binding with the catalytic pocket of α-glucosidase (pdb 3A4A). These findings indicated the excellent antidiabetic potential of the gallotannins from E. fischeriana, while 1,2,3-tri-O-galloyl-β-D-glucopyranose could be developed as a promising candidate for the treatment of T2DM with fewer side effects.