Received for publication February 2, 2007.
Revised May 31, 2007.
Accepted for publication June 5, 2007.

Isolation and Identification of Phase 1 Metabolites of Demethoxycurcumin in Rats

Abstract

Curcuminoids are a safe natural food coloring additive with anti-inflammatory, antioxidant and anticarcinogenic activities. Although demethoxycurcumin is one of the major bioactive constituents of curcuminoids, knowledge about its metabolic fate is scant. In the present study, four new metabolites: 5-dehydroxy-hexahydro-demethoxycurcumin-A (M-1), 5-dehydroxy-hexahydro-demethoxycurcumin-B (M-2), 5-dehydroxy-octahydro-demethoxycurcumin-A (M-3) and 5-dehydroxy-octahydro-demethoxycurcumin-B (M-4) were isolated from feces of male Wistar-derived rats and from urine, three new metabolites: 5-O-methyl-hexahydro-demethoxycurcumin-A (M-7), 5-O-methyl-hexahydro-demethoxycurcumin-B (M-8), and 5-dehydroxy-dihydro-demethoxycurcumin-B (M-9) and two known metabolites: hexahydro-demethoxycurcumin-A (M-5), hexahydro-demethoxycurcumin-B (M-6) were isolated. Their structures were established by chemical and spectral methods. All of them were reductive metabolites. Possibly of greater importance is that they occurred as pairs of isomers with a methoxyl group substituted on a different benzene ring. This finding in the metabolism of curcuminoids is reported here for the first. In addition, the 5-dehydroxy or 5-O-methylated metabolites are also novel finding. The fact that the metabolites occurred as pairs of the isomers suggests that demethoxycurcumin possibly undergoes tautomerization between 3-keto-5-enol (form A) and 3-keto-5-enol (form B) (Fig. 1) in rats. On the basis of the metabolite profiles, metabolic pathways of demethxoycurcumin in rats are proposed.

Key words: metabolite identification, structure elucidation