High-value utilization of Tamarindus indica L. shell in antiglycation: Focus on active polyphenol constituents and mechanism

Glycation promotes the generation of advanced glycation end products (AGEs), which in turn exacerbate inflammation, oxidative stress, and chronic metabolic disorders. Given the potential side effects associated with synthetic antiglycation agents, a natural polyphenol-based antiglycation agent was explored from the Tamarindus indica L. shell. In this study, Tamarindus indica L. shell polyphenols (TSP) were obtained via ultrasound-assisted extraction combined with AB-8 macroporous resin purification, which yielded the highest levels of phenolics and flavonoids. UPLC-Q-Orbitrap-MS² analysis identified 23 phenolic compounds, with flavonoids constituting the predominant class, including (+)-catechin, luteolin, and apigenin. TSP exhibited strong antiglycation activity, with dose-dependent inhibition of Amadori intermediates and AGEs. Mechanistic investigations revealed that TSP effectively trapped reactive carbonyl species (RCS), reduced protein oxidation and cross-linking, and maintained protein secondary structure. Spectroscopic analyses and molecular docking further confirmed stable noncovalent interactions between TSP constituents and key glycation-prone residues (arginine and lysine) in bovine serum albumin. Among the identified monomers, (+)-catechin, luteolin, apigenin, diosmetin, 4-hydroxybenzoic acid, procyanidin A2, and eriodictyol-7-O-glucoside exhibited the greatest antiglycation effects. Overall, this study demonstrated that TSP effectively inhibited glycation by trapping RCS, suppressing protein oxidation and structural alteration, and establishing specific interactions with key amino acid residues in proteins. The innovation of this study lies in systematically developing TSP as a novel natural antiglycation agent, demonstrating its multi-mechanistic efficacy and identifying key active constituents, thereby offering a sustainable strategy to valorize agricultural by-products.