The synergistic inhibition of isoginkgetin with miglitol and acarbose on α-glucosidase: Dynamics enzyme changes tracking

Isoginkgetin is an edible biflavone from ginkgo biloba leaves with many bioactivities. In this work, the inhibition and synergistic effect of isoginkgetin with miglitol or acarbose on saccharomyces cerevisiae α-glucosidase (α-SCG) were tracked via various spectroscopic techniques and computer simulations. Compared with miglitol or acarbose, isoginkgetin displayed more remarkable inhibition effect on α-SCG. In the presence of isoginkgetin, miglitol and acarbose exhibited stronger inhibitory effect on α-SCG than miglitol and acarbose alone. Isoginkgetin exerted the synergistic inhibitory effect by significantly increasing the binding affinity of acarbose or miglitol with α-SCG, leading to larger structural changes in α-SCG. The best binding mode, the stability of the formed complex, and the contribution of key amino acids to the binding were deeply analyzed via dynamics simulation. Isoginkgetin can be used as a strong inhibitor of α-SCG and synergistic inhibitor of miglitol or acarbose.