Screening of novel phytochemicals as secreted frizzled-related protein 4 inhibitors: An early stage biomarker of Type 2 diabetes

Abstract

Diabetes is increasing at an alarming rate worldwide with high mortality and posing severe health and economic burden. Secreted frizzled related protein 4 (SFRP4) is released from adipose tissues to suppress insulin exocytosis from β-cells of pancreas and acts as a biomarker for early detection of T2D. In present study, the 3D structure of human SFRP4 was predicted using comparative modeling approach and evaluated through online bioinformatics tools. The best predicted model of SFRP4 was used as a receptor in molecular docking studies. Phytochemicals from already reported antidiabetic plants were docked and screened using molecular operating environment (MOE) software to target SFRP4. The ligands were optimized and a database was constructed in MOE. Out of 850 compounds from 150 antidiabetic plants taken from PubChem database, singrin was found to be the most potent one with root mean square deviation (RMSD) value of 1.39, S-score of -10.06 and by interactions to five amino acids of SFRP4 active pocket. Furthermore, boeravinone E, boeravinone D, wedelolactone, squamosamide and taxifolin also interacted strongly to SFRP4 by exhibiting RMSD values of 1.00, 0.94, 1.89, 1.37, 1.28 and S-scores of -12.45, -11.26, -9.25, -7.26, -10.66, respectively. These phytochemicals are proposed to act as potential medicine for delaying the onset and treating T2D by specifically targeting SFRP4.