The Study Of The Absorption Of Curcumin In Caco-2Cell Model And In Rats Of Single-pass Intestinal Perfusion

ObjectiveCurcumin (diferuloylmethane), a yellow pigment in the spice turmeric (also called curry powder), has been used for centuries as a treatment for inflammatory diseases. Extensive research within the past two decades has shown that curcumin modulates several targets that have been linked with cancer and various other chronic diseases, and mediates its anti inflammatory effects through the downregulation of inflammatory transcription factors, enzymes and cytokines. The pharmacodynamics and pharmacokinetics of curcumin have been examined in animals and in humans. Although curcumin has been shown to one of the most important limitations with curcumin is its bioavailability. Mechanism of curcumin in vitro and in vivo are discussed in detail here. To determine the concentration of curcumin and study the absorption mechanism of curcumin in Caco-2cell monolayer model and in rats.MethodsThe intestine in rat was cannulated for in situ perfusion to study the absorption mechanism of curcumin. HPLC was used to determine the concentration of curcumin, The effect of drug concentration, time points and absorption site on the absorption had been studied. Caco-2cell monolayer model was applied to investigate the effects of conveying times, drug concentration, and other different drug, such as ketoconazole, verapamil and piperine on the absorption of curcumin. LC/MS was used to determine the concentration of curcumin and the apparent permeability coefficient (Papp) was calculated.ResultsThe concentration of curcumin had distinctive effect on the absorption kinetics of intestine but no distinctive effect on Kapp; Rate of intestinal absorption of curcumin showed cyclical fluctuations over time. And1h after the perfusion within the steady-state, the order of absorption rate constant (ka) was:40μg/ml>20μg/ml>80μg/ml; ka and Kapp of curcumin in the intestines showed no significant differences.(P>0.05). The order of Ka was:duodenum>ileum>jejunum>colon, and that of Kapp was: duodenum>jejunum>ileum>colon. Compared with the control group, ketoconazole, verapamil, and piperine have different promotive actions on Papp values of curcumin but not significant difference (P>0.05), while phenobarbitone as inhibitory role significantly.In the Caco-2cell monolayer model, the Papps of curcumin at different concentrations before the90min were ranked as follows:180μg/mL>240μg/mL>300μg/mL; Compared with the control group, a low concentration of ketoconazole, verapamil and piperine have different promotive actions on Papp values of curcumin (P<0.05).ConclusionThe saturation phenomenon of absorption of curcumin appears when in high concentrations, It is initially determined that absorption of curcumin is the active transport. And there exists obvious enterohepatic circulation in absorption of curcumin. And curcumin is completely absorbed at all segments of intestine in rats. There are no specific absorption window and no obvious absorption site.Curcumin was nonlinear absorbed at higher concentration and highest saturated concentration appeared, which indicated that the absorption of curcumin in both Caco-2cell model and in rats should be an active transport. It could be promoted by Ketoconazole inhibiting CYP3A4and1A2, Piperine inhibiting glucuronidase enzyme, and Verapamil inhibiting P-glycoprotein.