Evaluation of the effect of phenylpropanoids on the binding of heparin to human serum albumin and glycosylated human serum albumin concerning anticoagulant activity: A comparison study

Abstract

The nonenzymatic advanced glycation end products (AGEs) and the accumulation of AGEs are the two main factors associated with the long-term pathogenesis of diabetes. Human serum albumin (HSA) as the most abundant serum protein has a higher fortuity to be modified by nonenzymatic glycation. In this study, the interaction of three phenylpropanoids (caffeic acid (Caf), p-coumaric acid (Cou), and cinnamic acid (Cin)) toward HSA and glycosylated HSA (gHSA) was analyzed by multiple spectroscopic techniques combined with molecular docking. The formation of fibrils in HSA and gHSA was confirmed by the Thioflavin T (ThT) assay. The phenylpropanoids have shown anti-fibrillation properties in vitro. The obtained thermodynamic parameters indicated that hydrogen bonding and van der Waals forces are the main forces in the binding interaction, and the quenching mechanism of the protein fluorescence is static. Molecular docking results, as well as the in vitro results, showed that Caf, Cou, and Cin exhibit more stable interactions with HSA, respectively. In addition, molecular docking analysis showed that Caf and Cou interact well with K199. Given the critical role of K199 in HSA glycosylation in diabetic patients, this process inhibits the interaction of stabilizer compounds and thus accelerates gHSA aggregation.