Glyburide inhibits non-enzymatic glycation of HSA: An approach for the management of AGEs associated diabetic complications

Advanced glycation endproducts (AGEs) are the final product of glycation, highly reactive in nature and contribute directly or indirectly to numerous complications related to diabetes. In this study, the antiglycation activity of glyburide was investigated using HSA as model protein, both against glucose and methylglyoxal mediated glycation. The possible mechanism of action was also deciphered using biophysical and computational tools. Approximately 70% inhibition of both early and advanced glycation end products were recorded in the presence of glyburide. Free lysine modification was reduced by glyburide treatment and improvement in biochemical markers such as free thiol groups and carbonyl content was observed. Interaction studies revealed that glyburide showed moderate to strong binding affinity towards HSA with binding constant in the order of 10(6) M-1. The interaction of glyburide with HSA was entropically favourable and spontaneous in nature. Molecular dynamics simulation deciphered that glyburide-HSA complex was quite stable where RMSD, RMSF, R-g, SASA, and secondary structure of HSA remained approximately same over the entire simulation period. The average binding energy of the MD simulation for glyburide-HSA complex was found to be -15.386 kJ mol(-1). The findings demonstrate the antiglycation potential of glyburide and its possible mechanism of action. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

Glyburide exhibits significant antiglycation activity, reducing the formation of early and advanced glycation end products by decreasing free lysine modification and enhancing biochemical markers. Additionally, glyburide shows strong binding affinity towards HSA, with binding process being entropically favorable and spontaneous.