Biotransformation of curcumin through reduction and glucuronidation in mice

Curcumin, the yellow pigment in turmeric and curry, has antioxidative and a nticarcinogenic activities, In this study, we investigated the pharmacokine tic properties of curcumin in mice. After i.p. administration of curcumin ( 0.1 g/kg) to mice, about 2.25 mu g/ml of curcumin appeared in the plasma in the first 15 min. One hour after administration, the levels of curcumin in the intestines, spleen, liver, and kidneys were 177.04, 26.06, 26.90, and 7.51 mu g/g, respectively. Only traces (0.41 mu g/g) were observed in the b rain at 1 h. To clarify the nature of the metabolites of curcumin, the plas ma was analyzed by reversed-phase HPLC, and two putative conjugates were ob served, Treatment of the plasma with beta-glucuronidase resulted in a decre ase in the concentrations of these two putative conjugates and the concomit ant appearance of tetrahydrocurcumin (THC) and curcumin, respectively. To i nvestigate the nature of these glucuronide conjugates in vivo, the plasma w as analyzed by electrospray. The chemical structures of these metabolites, determined by mass spectrometry/mass spectrometry analysis, suggested that curcumin was first biotransformed to dihydrocurcumin and THC and that these compounds subsequently were converted to monoglucuronide conjugates. Becau se THC is one of the major metabolites of curcumin, we studied its stabilit y at different pH values. IHC was very stable in 0.1 M phosphate buffers of various pH values. Moreover, IHC was more stable than curcumin in 0.1 M ph osphate buffer, pH 7.2 (37 degrees C), These results, together with previou s findings, suggest that curcumin-glucuronoside, dihydrocurcumin-glucuronos ide, THC-glucuronoside, and THC are major metabolites of curcumin in vivo.