Inhibition of insulin amyloid fibril formation by ferulic acid, a natural compound found in many vegetables and fruits

Abstract

The highly ordered structures from the self-assembly of proteins/peptides, referred to as amyloid fibrils, are the major cause for many neurodegenerative diseases. Herein, we have analyzed the effect of ferulic acid (FA), one of the most abundant phenolic acids in plants, fruits and vegetables, on the inhibition of insulin (associated with type II diabetes) fibrillation. It was found that the amount of fibril formation was greatly reduced with increasing concentration of FA as evidenced from turbidity measurements. ThT binding experiments confirm the inhibition in which enhanced fluorescence, characteristic of amyloid fibrillation, was not observed in the presence of FA. Atomic force microscopy further confirms inhibition by FA where no typical insulin amyloid fibril has been detected. The characteristic conformational transition from α-helix to β-sheet was arrested in the presence of FA demonstrating that FA protects the native structure of insulin and thereby prevents the conformational change required for its amyloid fibril formation in vitro. The percentage of insulin fibril inhibition was found to be dependent on the concentration of FA. The current results demonstrate that FA can inhibit the insulin amyloid fibril formation and thus FA, in addition to other phenolic compounds, provides a possible therapeutic strategy to prevent or treat insulin amyloidosis.