Bioavailabilty Studies of Curcuminoids: Lessons Learned and the Need for Labeled Reference Materials
Turmeric, the rhizome of the plant Curcuma longa L., has been used for centuries in Ayurvedic medicine for the treatment of different diseases. Curcuminoids – curcumin, demethoxy-curcumin, and bisdemethoxy-curcumin – represent the major active constituents of turmeric. It is essential to determine the bioavailability of curcuminoids, the ability to deliver the active ingredient to the bloodstream. However, since curcuminoids have high hydrolytic instability at physiological pH and poor intestinal absorption, their presence in blood/plasma is very low. Radiolabeled materials are excellent tools to assess the difference between the amount of compound absorbed and metabolized during first pass through the intestine and liver. But, synthesis of radiolabeled analogues is costly and the analysis requires special facility and equipment, therefore the use of labeled compounds in botanical research is very limited. Without available labeled compounds, the bioavailability of curcuminoids is measured using various analytical techniques such as gas chromatography, capillary electrophoresis with amperometric detection, liquid chromatography (LC) with UV or photodiode array detection, LC-tandem mass spectrometry and matrix assisted laser desorption/ionization. Human colon carcinoma-derived cell line Caco-2 can also be used to estimate bioavailability. The apparent permeability coefficient P app is generally acknowledged as predictive for in vivo bioavailability: P app <1 indicates less than 20%, absorption. Our experiments showed that when differentiated Caco-2 cells were exposed to curcumin, the major basolateral products were hexahydro-curcumin sulfate, small amounts of curcumin-glucuronide and octahydro-curcumin sulfate; confirming the rapid reduction of curcumin. For curcumin, a P app of 0.03–0.07 was calculated, indicating virtually no bioavailability of the non-metabolized compound. For metabolites, P app was 0.5–1.3 suggesting low bioavailability of the metabolites.