Dry Heating of Curcumin in the Presence of Basic Salts Yields Anti-inflammatory Dimerization Products.

Curcumin exerts some of its biological effects via degradation products formed by spontaneous oxidation at physiological, i.e., weakly basic, pH. Here, we analyzed products formed by dry heating of curcumin in the presence of a basic salt (sodium bicarbonate and others). Under the dry heating conditions employed, curcumin was completely consumed, yielding products entirely different from those obtained by autoxidative degradation in buffer. Bioassay-guided fractionation of the reaction mixture was used to identify and isolate compounds with anti-inflammatory activity in a cell-based assay. This provided two dimers of curcumin, dicurmins A and B, featuring a partly saturated naphthalene core that inhibited lipopolysaccharide-induced activation of NF-κB in RAW264.7 cells. Dicurmin A and B are unusual derivatives of curcumin lacking key functional moieties yet exhibit increased anti-inflammatory activity. The process of dry heating of polyphenols in the presence of a basic salt can serve as a novel approach to generating bioactive compounds.