Autooxidation of curcumin in physiological buffer causes an enhanced synergistic anti-amyloid effect

Curcumin is an important food additive that shows multiple medical-benefits including anticarcinogenic, anti-inflammatory, antibiotic and antiamyloid properties. However, understanding the mechanism of curcumin-mediated effects becomes rather complicated since it has low bio-viability and it undergoes autooxidation, influenced by temperature, pH and buffer. We find that curcumin's antiamyloid-potential is not primarily due to curcumin alone, rather due to a synergistic action of curcumin and its autooxidized-products generated during inhibition reactions. In physiological buffer curcumin undergoes thermally induced autooxidation and yields stable compounds which can synergistically work for both inhibition of amyloid aggregation and promotion of amyloid-disaggregation into soluble protein species. Curcumin also showed substantial inhibition effect against coaggregation of different food proteins. Curcumin's strong affinity for the hydrophobic moieties of the aggregation-prone partially-folded insulin structures seems crucial for the inhibition mechanism. Further, autooxidized curcumin products were found to protect UV-induced protein damage. The results provide conceptual foundations highlighting the link between chemistry and antiamyloid-activity of curcumin and may inspire curcumin-based therapeutics against amyloidogenesis.