In silico modeling of aspalathin and nothofagin against SGLT2

Abstract

Aspalathin and nothofagin are the major dihydrochalcones found in rooibos (Aspalathus linearis), which display anti-diabetic activities, but the mechanism is still unclear. In this paper, hSGLT2 (human sodium dependent glucose co-transporter 2), a target for diabetes mellitus, was built using homology modeling method. Molecular docking and dynamics simulations were carried out on aspalathin, nothofagin and SGLT2 complexes with dapagliflozin as positive control. The results show that both the binding energies and binding modes of aspalathin and nothofagin are similar to dapagliflozin, indicating that either component of rooibos may exhibit anti-diabetic effects through inhibiting SGLT2 receptor. However, the predicted permeability value of aspalathin and nothofagin is low, which may cause poor absorption, resulting in weak SGLT2 inhibition. Calculation results elucidate the possible inhibiting mechanism of aspalathin and nothofagin against SGLT2, and therefore enhance our understanding of anti-diabetic activities of rooibos.