Insulin Complexation with Curcumin Cysteine Complex (CCC) Mitigates Amyloidosis and Efficiently Manages Diabetes in Drosophila

Insulin, a peptide hormone crucial for managing diabetes mellitus, frequently aggregates at recurrent injection sites in patients. These aggregates form insoluble insulin fibrils, leading to localized inflammatory reactions and impaired insulin uptake, which compromises therapeutic efficacy. Current insulin formulations lack robust strategies to prevent this amyloidosis. Phytochemicals, recognized for their anti-fibrillating properties, present a promising avenue to stabilize insulin and enhance its therapeutic potential by preventing aggregation, thereby addressing a critical gap in long-term diabetes care.

Researchers investigated the anti-fibrillating potential of three phytochemicals—Mangiferin (Mg), Rosmarinic Acid (RA), and Curcumin Cysteine Complex (CCC)—on insulin at physiological pH. In vitro studies assessed their ability to inhibit insulin fibrillation in a dose-dependent manner. For in vivo evaluation, HSF-induced diabetic Drosophila melanogaster were treated with formulations of insulin complexed with each phytochemical, compared against monomeric insulin alone. The primary endpoint was the mitigation of diabetic traits and restoration of normal physiology in the flies.

Both Curcumin Cysteine Complex (CCC) and Rosmarinic Acid (RA) efficiently inhibited insulin fibrillation in vitro in a dose-dependent manner. This inhibition was attributed to their binding to the aggregation-prone regions of the insulin protein, suggesting a direct mechanism of action.

In vivo experiments in HSF-induced diabetic Drosophila revealed that treatments with insulin-phytochemical formulations were significantly more therapeutically effective in mitigating diabetic traits than monomeric insulin alone. Among the tested phytochemicals, the insulin formulation with CCC demonstrated the most pronounced efficacy in restoring normal physiological parameters in the diabetic flies. This superior performance of CCC suggests its strong potential to stabilize insulin formulations against both in vitro and in vivo amyloidosis, offering a robust strategy for enhanced therapeutic outcomes.