Differential effect of biophenols on attenuation of AGE-induced hemoglobin aggregation

Despite most studied activities of natural biophenols rely on antioxidant properties, little clues explored their key structural components with regard to opposing action on glycation-induced aggregation. Herein, human hemoglobin (hHb)/fructose system used to decipher if structural peculiarities of two biophenols "chlorogenic acid (CGA) and curcumin (CUR)" are effective toward AGEs-bridged aggregate formation. Suppression in amyloid cross-β formation was monitored by CD spectroscopy, fluorescence microscopy, ANS and AGE fluorescence. Reduction in molten globule structure of modified-Hb by CGA was corroborated with helix structure, thiol group and lysine residues content estimation for native, glycated and biophenols treated samples. ThT and Congo red assays showed the cross-β breaking properties of CGA. Molecular docking outcomes revealed the positioning of CGA/CUR is driven by "aromatic interactions" with Trp β₁180 and Tyr α₂540. These interactions are modulated by the structural constraints such as number of hydroxyl groups and their methylation status directing the biophenols to the amyloidogenic core. The results are applicable to formulation of small-molecule nutraceuticals for treatment of conformational diseases.