A high-resolution α-glucosidase inhibition profiling for targeted identification of natural antidiabetic products from (L.) Pic. Serm and their inhibitory mechanism study.

The targeted identification of α-glucosidase inhibitors from the crude ethyl acetate of (L.) Pic. Serm () was guided by high-resolution inhibition profiling. The α-glucosidase inhibition profiling and HPLC-QTOF-MS showed tannins and serratenes were the corresponding antidiabetic constituents. Two new serratenes named 3β, 21β-dihydroxyserra-14-en-24-oic acid-3β-(4'-methoxy-5'-hydroxybenzoate) (), 3β, 21α-dihydroxyserra-14-en-24-oic acid-3β-(4'-methoxy-5'-hydroxybenzoate) (), together with two known compounds ( and ) were isolated. Their structures were elucidated by HR-ESI-MS and NMR. Compounds - inhibited the α-glucosidase activity in a non-competitive manner with Ki values ranging from 1.29 to 12.9 µM. The molecular docking result unveiled that - bound to the residues at the channel site, which enabled to block the substrate access. In addition, the molecular dynamics (MD) simulation of the most active compound and α-glucosidase indicated the 4'-methoxy-5'-hydroxybenzoate group formed the stable hydrogen bonds and pi-pi T-shaped interactions with Arg312, Gln350 and Phe300 residues, while the rings D and E were stabilized by hydrophobic interaction.