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 a-helix to b-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.

Gelatin as a Potential Inhibitor of Insulin Amyloid Fibril Formation

“…We have previously shown that FA, a phenolic compound, has a capability of inhibiting insulin fibrillation, which was concentration dependent. To grasp the overall inhibitory efficiency of a mixture containing gelatin and FA, we had selected a concentration of FA (0.034 mg mL −1 ) and gelatin (0.3 wt%) at which they elicited an average inhibitory activity when they tested individually. As can be seen from figure 6 A, during the progress of the fibril formation, absorbance at 600 nm is significantly reduced in the presence of gelatin:FA mixture compared to their individual inhibitory efficiency, indicating the less amyloid fibrillation.…”

“…Because gelatin is commonly used to make capsules (enclosed shell of medicines), we have also tested the efficiency of a known insulin amyloid inhibitor such as FA, as an example, in the presence of gelatin against insulin fibrillogenesis. We have previously shown that FA, a phenolic compound, has a capability of inhibiting insulin fibrillation, which was concentration dependent. To grasp the overall inhibitory efficiency of a mixture containing gelatin and FA, we had selected a concentration of FA (0.034 mg mL −1 ) and gelatin (0.3 wt%) at which they elicited an average inhibitory activity when they tested individually.…”

Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications

“…Jayamani et al demonstrated the inhibitory effect of ferulic acid on insulin amyloid fibril formation. The minimum molar ratio of insulin:ferulic acid (1:10) displayed the maximum inhibition of insulin fibrillation approximately 85% [ 131 ]. Ferulic acid prevented the conformational transition from α-helix to β-sheet.…”

“…Ferulic acid prevented the conformational transition from α-helix to β-sheet. Molecular docking analysis revealed that the phenyl, hydroxyl and carboxylic moieties of ferulic acid interact with insulin through hydrogen bonds as well as hydrophobic interactions [ 131 ]. It is proposed that ferulic acid can be considered for delaying the growth of amyloidosis.…”

Inhibitory effect of coumarin and its analogs on insulin fibrillation /cytotoxicity is depend on oligomerization states of the protein

“…Among all these routes, based on centuries of coexistence between humans and plants, the use of phytochemicals for this purpose has received more attention. Along this line of strategy, the use of phenolic compounds such as curcumin, [11][12][13] gallic acid, 14 ferulic acid, 15 quercetin, 16 etc. have attracted a lot of attention.…”