Inhibition Mechanism of Sanggenone D/ Kuwanon G Against α-Glucosidase and the Regulation of Glucose via GLUT4 Pathway

Inhibition of α-glucosidase activity is considered to be an effective treatment for type 2 diabetes. The inhibitory mechanisms of sanggenone D and kuwanon G on α-glucosidase were investigated and the pathways for hypoglycemic effects were explored in the current study. The outcomes indicated that sanggenone D (IC50: 4.51 × 10-5 mol/L) and kuwanon G (IC50: 3.83 × 10-5 mol/L) inhibited α-glucosidase activity by non-competition/anti-competition mixed inhibition and competitive inhibition, respectively. Besides, the secondary structure of α-glucosidase were altered by static quenching, and exhibited the decrease in α-helix, β-antiparallel content, while increase in β-sheet content. Furthermore, the interaction forces between sanggenone D/kuwanon G and α-glucosidase were hydrophobic interactions and hydrogen bonds as evidenced by molecular docking. The binding affinity, stability and binding energy aligned with the results of IC50. Cyclization in sanggenone D structure resulted in a decrease in the number of phenolic hydroxyl groups and thus a reduction in the formation of hydrogen bonds, which ultimately diminished the binding affinity of sanggenone D to α-glucosidase. In addition, western blot results showed that sanggenone D and kuwanon G regulated glucose metabolism by activating of GLUT4 pathway.