In silico modeling and in vitro activity of vitexin and isovitexin against SGLT2

Abstract

The homology model of hSGLT2 (human sodium dependent glucose co-transporter 2) was used as a target for diabetes mellitus. Molecular docking and dynamics simulations were carried out on vitexin- and isovitexin-SGLT2 complexes with dapagliflozin as positive control. The results show that both vitexin and isovitexin have weaker binding energies compared to dapagliflozin, indicating that both ligands may exhibit weak anti-diabetic effects through inhibiting SGLT2. The poor binding mode of vitexin and isovitexin may be responsible for their weak anti-diabetic effect. These results are in accordance with the inhibitory activity against hSGLT2 in vitro test with the inhibitory rate 26.3% of vitexin and 11.2% of isovitexin at the dose of 10[Formula: see text][Formula: see text]mol[Formula: see text][Formula: see text][Formula: see text]L[Formula: see text]. The results of calculation and in vitro test may explain the possible inhibiting mechanism of vitexin and isovitexin against SGLT2, and therefore enhance our understanding of the structure-activity relationships of SGLT2 inhibitors.