This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ireson, C. R. Articles by Gescher, A. J. Search for Related Content PubMed PubMed Citation Articles by Ireson, C. R. Articles by Gescher, A. J.

Metabolism of the Cancer Chemopreventive Agent Curcumin in Human and Rat Intestine

Medical Research Council Toxicology Unit, University of Leicester, Leicester LE1 9HN, United Kingdom [C. R. I., D. J. L. J., D. J. B., P. B. F., A. J. G.]; Human Tissue Bank and School of Pharmacy and Pharmaceutical Sciences, De Montfort University, Leicester LE1 9BH, United Kingdom [S. O.]; Department of Molecular and Cellular Pathology, University of Dundee, Ninewells Hospital & Medical School, Dundee DD1 9SY, United Kingdom [M. W. H. C.]; and Department of Oncology, University of Leicester, Leicester LE1 5WW, United Kingdom [M. L. W., W. P. S.]

Curcumin, the yellow pigment in turmeric, prevents malignancies in the intestinal tract of rodents. It is under clinical evaluation as a potential colon cancer chemopreventive agent. The systemic bioavailability of curcumin is low, perhaps attributable, at least in part, to metabolism. Indirect evidence suggests that curcumin is metabolized in the intestinal tract. To investigate this notion further, we explored curcumin metabolism in subcellular fractions of human and rat intestinal tissue, compared it with metabolism in the corresponding hepatic fractions, and studied curcumin metabolism in situ in intact rat intestinal sacs. Analysis by high-performance liquid chromatography, with detection at 420 or 280 nm, permitted characterization of curcumin conjugates and reduction products. Chromatographic inferences were corroborated by mass spectrometry. Curcumin glucuronide was identified in intestinal and hepatic microsomes, and curcumin sulfate, tetrahydrocurcumin, and hexahydrocurcumin were found as curcumin metabolites in intestinal and hepatic cytosol from humans and rats. The extent of curcumin conjugation was much greater in intestinal fractions from humans than in those from rats, whereas curcumin conjugation was less extensive in hepatic fractions from humans than in those from rats. The curcumin-reducing ability of cytosol from human intestinal and liver tissue exceeded that observed with the corresponding rat tissue by factors of 18 and 5, respectively. Curcumin sulfate was identified in incubations of curcumin with intact rat gut sacs. Curcumin was sulfated by human phenol sulfotransferase isoenzymes SULT1A1 and SULT1A3. Equine alcohol dehydrogenase catalyzed the reduction of curcumin to hexahydrocurcumin. The results show that curcumin undergoes extensive metabolic conjugation and reduction in the gastrointestinal tract and that there is more metabolism in human than in rat intestinal tissue. The pharmacological implications of the intestinal metabolism of curcumin should be taken into account in the design of future chemoprevention trials of this dietary constituent.

This article has been cited by other articles:

				Y. Zeng, F. Qiu, Y. Liu, G. Qu, and X. Yao Isolation and Identification of Phase 1 Metabolites of Demethoxycurcumin in Rats Drug Metab. Dispos., September 1, 2007; 35(9): 1564 - 1573. [Abstract] [Full Text] [PDF]

				W. Zhang, T. M. C. Tan, and L.-Y. Lim Impact of Curcumin-Induced Changes in P-Glycoprotein and CYP3A Expression on the Pharmacokinetics of Peroral Celiprolol and Midazolam in Rats Drug Metab. Dispos., January 1, 2007; 35(1): 110 - 115. [Abstract] [Full Text] [PDF]

				T. Sicilia, A. Bub, G. Rechkemmer, K. Kraemer, P. P. Hoppe, and S. E. Kulling Novel Lycopene Metabolites Are Detectable in Plasma of Preruminant Calves after Lycopene Supplementation J. Nutr., November 1, 2005; 135(11): 2616 - 2621. [Abstract] [Full Text] [PDF]

				J. Fang, J. Lu, and A. Holmgren Thioredoxin Reductase Is Irreversibly Modified by Curcumin: A NOVEL MOLECULAR MECHANISM FOR ITS ANTICANCER ACTIVITY J. Biol. Chem., July 1, 2005; 280(26): 25284 - 25290. [Abstract] [Full Text] [PDF]

				M. F. McCarty Targeting Multiple Signaling Pathways as a Strategy for Managing Prostate Cancer: Multifocal Signal Modulation Therapy Integr Cancer Ther, December 1, 2004; 3(4): 349 - 380. [Abstract] [PDF]

				Y. Song, N. D. Sonawane, D. Salinas, L. Qian, N. Pedemonte, L. J. V. Galietta, and A. S. Verkman Evidence against the Rescue of Defective {Delta}F508-CFTR Cellular Processing by Curcumin in Cell Culture and Mouse Models J. Biol. Chem., September 24, 2004; 279(39): 40629 - 40633. [Abstract] [Full Text] [PDF]

				S. Nowell, D. L. Ratnasinghe, C. B. Ambrosone, S. Williams, T. Teague-Ross, L. Trimble, G. Runnels, A. Carrol, B. Green, A. Stone, et al. Association of SULT1A1 Phenotype and Genotype with Prostate Cancer Risk in African-Americans and Caucasians Cancer Epidemiol. Biomarkers Prev., February 1, 2004; 13(2): 270 - 276. [Abstract] [Full Text] [PDF]

				Curcumin Derivatives: Potential for Prostate Cancer Management: ADDANKI P. KUMAR, GRETCHEN E. GARCIA, RITA GHOSH, RAJENDRAN V. RAJNARAYANAN,1 WILLIAM L. ALWORTH,1 AND THOMAS J. SLAGA, Center for Cancer Causation and Prevention, AMC Cancer Research Center and University of Colorado Comprehensive Cancer Center, Denver, Colorado 80214; 1 Department of Chemistry, Tulane University, New Orleans, Louisiana 70118 Toxicol Pathol, January 1, 2004; 32(1): 161 - 163. [PDF]

				H.-L. Fang, S. Shenoy, Z. Duanmu, T. A. Kocarek, and M. Runge-Morris TRANSACTIVATION OF GLUCOCORTICOID-INDUCIBLE RAT ARYL SULFOTRANSFERASE (SULT1A1) GENE TRANSCRIPTION Drug Metab. Dispos., November 1, 2003; 31(11): 1378 - 1381. [Abstract] [Full Text] [PDF]