Exploring The Role of Phytochemicals as Anti-Fibrillating Agents for Insulin Amyloidosis

Abstract

Insulin, a peptide hormone commonly used in the therapeutic management of diabetes mellitus, undergoes aggregation at sites of recurrent injections in diabetic patients, as well as during its industrial synthesis and transportation. These aggregates are comprised of insoluble insulin fibrils and can lead to localized inflammatory reactions, and impaired insulin uptake. Therefore, it is essential to formulate strategies aimed at inhibiting insulin aggregation for therapeutic and industrial applications. Phytochemicals that exhibit anti-fibrillating properties have shown promising efficacy in the mitigation of insulin amyloidosis. In this study we have enlightened the effects of Curcumin cysteine complex (CCC, a derivative of curcumin) and Rosmarinic acid (RA) as anti-fibrillating agents of Insulin at physiological pH. CCC and RA efficiently inhibit insulin fibrillation in dose-dependent manner as deduced from Thioflavin T fluorescence and TEM micrographs. These compounds bind to the anti-amyloidogenic regions in the protein as inferred from the MD simulation studies, which can be a plausible mechanism behind their anti-fibrillating properties and reduced cytotoxicity as compared to insulin fibrils. Therefore, these phytochemicals may hold the key to preventing fibrillation of insulin, offering potential benefits for both therapeutics and bio-medical applications.