Unveiling the Role of Mg2+ and Mn2+ in Theaflavin-Mediated Inhibition of Advanced Glycation End Products Formation: Mechanistic Insights from Intermolecular Interaction
TL;DR
It was concluded that free radical scavenging contributes more significantly to AGE inhibition than does blocking the glycation sites on HSA, providing insights for the prevention and management of chronic diseases.
Abstract
Advanced glycation end products (AGEs) are implicated in the pathogenesis of chronic diseases. This study investigated the inhibitory effect of theaflavin (TA) on AGE formation in a human serum albumin (HSA)-fructose model system, both in the absence and presence of non-cytotoxic Mg2+ or Mn2+. The underlying mechanism was elucidated using multiple spectroscopic techniques and molecular docking. TA significantly inhibited AGE formation, with the enhancement by metal ions following the order: 1.5 μM Mn2+ > 1.5 μM Mg2+ > 1 mM Mg2+. This trend aligned with the binding affinity between HSA and TA derived from molecular interaction studies. Site marker competition and docking results revealed that TA binds preferentially within subdomain IIA of HSA. Furthermore, the conformational changes in HSA following glycation and inhibition were monitored, along with the influence of metal ions on the antioxidant activity of TA. By integrating the results, it was concluded that free radical scavenging contributes more significantly to AGE inhibition than does blocking the glycation sites on HSA. Overall, this study elucidates the influence of metal ions on the inhibitory effect of TA against AGE formation and the corresponding mechanism, providing insights for the prevention and management of chronic diseases.