Elucidating the Antiglycation Effect of Apigenin Glycosides on Ribosylation of Albumin, Multi-Spectroscopic and Molecular Docking Analyses

A comparative study was carried out to explore the antiglycation potential and mechanisms of apigenin (AP) and its glycosidic derivatives, apigenin-4'-O-glucoside (A4′G) and apigenin-7-O-glucoside (A7G), in the reaction mixtures of ribose and human serum albumin (HSA). The degree of ribosylation was monitored by ANS and AGE-specific fluorescence, UV-vis spectroscopy, confocal microscopy, TNBS, DTNB, DNPH assays, and in silico evaluation. The significant decrease in esterase-like activity of ribosylated HSA was strongly improved by the presence of glycosidic derivatives (A4'G > A7G). Despite the higher ability of A4'G to quench AGE-specific fluorescence, the superior capacity of both glycosidic derivatives to reduce the “cross-β structures” of ribosylated-HSA was confirmed by ThT fluorescence. Moreover, A4'G/A7G (10 μM) showed considerable protection against side chain modifications at lysine and cysteine residues, corroborated by TNBS, and DTNB assays for native, glycated and APs-treated HSA. Molecular docking analysis revealed that glycosidic derivatives (A4'G > A7G) could alleviate ribosylation by protecting the glycation- prone sites in Sudlow site I. An explanation was provided regarding the relationship between the effectiveness of glycoside derivatives in suppressing advanced HSA ribosylation and their structural features. Overall, a thorough understanding of the mechanisms underlying AP derivatives in suppressing protein glycation paves the way for the design of "lead molecules" beyond conventional therapies.