Protopanaxadiol (PPD)-type ginsenosides inhibit the key element of α-glucosidase - The glycosyl group.

In this study, the inhibitory effects of ten protopanaxadiol (PPD)-type ginsenosides on α-glucosidase in vitro were firstly investigated, and selected four ginsenosides with stronger inhibitory effects, namely CY, C-Mc, F2 and CK. The kinetic results of enzyme inhibition indicated that CY, C-Mc, F2 and CK were all non-competitive inhibitors of α-glucosidase. Fluorescence quenching and circular dichroism (CD) analyses showed that the inhibition of α-glucosidase by CY, C-Mc, F2, and CK was a static process, and that they altered the structure of α-glucosidase. The interaction of the four ginsenosides with α-glucosidase was a spontaneous reaction, mainly driven by hydrogen bonding. At 298 K, the binding constants of CY, C-Mc, F2, and CK with α-glucosidase were 0.70 × 10 mol/L, 0.75 × 10 mol/L, 1.46 × 10 mol/L, 1.65 × 10 mol/L respectively, and the number of binding sites was about 1 for all of them. The molecular docking results showed that CY, C-Mc, F2 and CK bound to sites other than the active center of the α-glucosidase through hydrogen bonds. All the above results showed the structure and hypoglycemic effects of CY, C-Mc, F2 and CK, and they can be used as potential α-glucosidase inhibitors for the treatment of Type 2 diabetes mellitus (T2DM).