Mechanisms of Isoliquiritigenin Against Protein Glycation: A Comparative Study in PBS Solution and Crowding Environment

The advanced glycation end products generated from protein glycation are associated with the development of diabetic complications. This study aimed to investigate the inhibitory mechanisms of isoliquiritigenin on protein glycation and compare its anti-glycation activity in PBS versus a macromolecular crowding environment. The results showed that in PBS, 500 μmol/L isoliquiritigenin showed an advanced glycation end product inhibition rate of 37.78%, outperforming aminoguanidine. Meanwhile, isoliquiritigenin inhibited the protein carbonylation process, reduced the generation of protein oxidation products, and inhibited the formation of β-crosslinking structures with a rate of 34.20%. Molecular docking results indicated that isoliquiritigenin bound to site I of bovine serum albumin, effectively blocked glycation reactions by occupying multiple arginine residues and contributed to stabilizing the secondary structure of bovine serum albumin. In addition, isoliquiritigenin exhibited significant hydroxyl radical scavenging and Fe2+-chelating abilities, achieving a 34.35% trapping efficiency for methylglyoxal. Isoliquiritigenin exerted its anti-glycation activity through multiple pathways, including scavenging free radicals, protecting protein structure, interacting with bovine serum albumin, and trapping methylglyoxal. However, in the crowding environment, the excluded volume effect and higher viscosity might lead to limited isoliquiritigenin binding to bovine serum albumin, reducing its inhibition of glycation and decreasing advanced glycation end product inhibition to 16.38%. This study realistically evaluated the inhibitory effects of isoliquiritigenin in complex crowding environments and provided a theoretical basis for isoliquiritigenin as a functional food ingredient for the prevention of diabetes complications. Future studies need to establish animal models to further explore its effects in vivo.