Putative Cancer Chemopreventative Agents of Dietary Origin - How Safe Are They?

Putative Cancer Chemopreventative Agents of Dietary Origin - How Safe Are They

Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine

Purpose: Curcumin, a major constituent of the spice turmeric, suppresses expression of the enzyme cyclooxygenase 2 (Cox-2) and has cancer chemopreventive properties in rodents. It possesses poor systemic availability. We explored whether formulation with phosphatidylcholine increases the oral bioavailability or affects the metabolite profile of curcumin. Methods: Male Wistar rats received 340 mg/Kg of either unformulated curcumin or curcumin formulated with phosphatidylcholine by oral gavage. Rats were killed at 15, 30, 60 and 120 min post intubation. Plasma, intestinal mucosa and liver were analysed for the presence of curcumin and metabolites using HPLC with UV detection. Identity of curcumin and metabolites was verified by negative ion electrospray liquid chromatography/tandem mass spectrometry. Results: Curcumin, the accompanying curcuminoids desmethoxycurcumin and bisdesmethoxycurcumin, and the metabolites tetrahydrocurcumin, hexahydrocurcumin, curcumin glucuronide and curcumin sulfate were identified in plasma, intestinal mucosa and liver of rats which had received formulated curcumin. Peak plasma levels and area under the plasma concentration time curve (AUC) values for parent curcumin after administration of formulated curcumin were five-fold higher than the equivalent values seen after unformulated curcumin. Similarly, liver levels of curcumin were higher after administration of formulated curcumin as compared to unformulated curcumin. In contrast, curcumin concentrations in the gastrointestinal mucosa after ingestion of formulated curcumin were somewhat lower than those observed after administration of unformulated curcumin. Similar observations were made for curcumin metabolites as for parent compound. Conclusion: The results suggest that curcumin formulated with phosphatidylcholine furnishes higher systemic levels of parent agent than unformulated curcumin