Mesalazine Inhibits amyloid formation and destabilizes pre-formed amyloid fibrils in the human insulin

Abstract

Amyloid formation due to protein aggregation is associated with several amyloid diseases (amyloidosis). The use of small organic ligands as inhibitors of protein aggregation is an attractive strategy to treatments for these diseases. In the present study, we evaluated the in vitro inhibitory and destabilizing effects of Mesalazine on human insulin protein fibrillation. To induce fibrillation, human insulin was incubated in 50 mM glycine buffer (pH 2.0) at 50°C. The effect of Mesalazine on insulin amyloid aggregation was studied using spectroscopic, imaging, and computational approaches. Based on the results, the Mesalazine in a concentration dependent manner (different ratios (1:0.1, 1:0.5, 1:1 and 1:5) of the insulin to Mesalazine) prevented the formation of amyloid fibrils and destroyed pre-formed fibrils. In addition, our molecular docking study confirmed the binding of Mesalazine to insulin through hydrogen bonds and hydrophobic interactions. Our findings suggest that Mesalazine may have therapeutic potential in the prevention of insulin amyloidosis and localized amyloidosis.