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.
Alrehaili et al. (Sun,) studied this question.