Fabricating Silver Nanoparticles with Antidiabetic d-Pinitol to Restrict Amyloid Formation of Insulin

In this study, we synthesized silver nanoparticles functionalized with antidiabetic d-pinitol molecules and investigated their anti-amyloid effect on Insulin aggregation. Our results show that these functionalized nanoparticles effectively inhibit both spontaneous and seed-induced amyloid aggregation of Insulin in a dose-dependent manner. The d-pinitol-functionalized silver nanoparticles interact directly with the aggregation-prone regions of Insulin's partially unfolded structures, as demonstrated by quenching and computational experiments. Analysis of docking and simulation data suggests that antiamyloid activity of d-pinitol functionalized AgNPs is due to a strong Insulin-nanoparticle interaction, facilitated via hydrogen bonds. These interactions disrupt the Insulin monomer-dimer equilibrium and prevent the formation of toxic amyloid structures. The results could lead to the development of d-pinitol-based Insulin-stabilizing nanoformulations with potential antidiabetic properties.