Inhibition of Glucose-Induced Glycation of HSA by Pioglitazone: Multi-Spectroscopic and Bioinformatic Evidence.

Diabetes mellitus is a growing health concern that causes numerous complications. Glycation produces advanced glycation end-products (AGEs), which promote diabetic complications. Targeting glycation is a strategy for combating the progression of diabetic complications. Pioglitazone enhances insulin sensitivity in patients with type 2 diabetes mellitus, but its impact on glycation remains unclear. This study aims to evaluate whether pioglitazone can inhibit glucose-induced glycation of human serum albumin (HSA), using in vitro assays and in silico tools. Pioglitazone inhibited >70% of early glycation products and >75% of AGEs. The treatment also reduced free lysine modification and improved biochemical markers, including carbonyl and free thiol levels. Pioglitazone exhibited moderate binding affinity for HSA, with a binding constant of 104 M-1. The interaction between pioglitazone and HSA was both spontaneous and entropically favourable. Molecular dynamics simulations revealed that the HSA-pioglitazone complex remained quite stable, with RMSF, RMSD, SASA, Rg, and HSA's secondary structure showing minimal changes throughout the simulation. The overall binding energy for HSA-pioglitazone complex formation was -30.06 ± 0.31 kcal mol-1, as obtained from MD simulations. The findings suggest that pioglitazone likely interacts with glycation-prone regions of HSA, as indicated by spectroscopic and docking analyses, and contributes to the reduction of glycation.