Study On The Absorption And Transport Of Curcumin And Its Analogues Using Caco-2 Cell Monolayers

Curcumin（Cur）is a strong natural antioxidant,who can prevent multiple diseases such as anti-cancer,anti-inflammatory,anti-alzheimer’s disease and various malignant diseases.But it has poor oral bioavailability due to the instability,as well as its poor aqueous solubility,which limited its application in clinical.While its novel analogues（CB and FE）prepared by our group,showed better anti-oxidant activity,better anti-tumor activity and better stability than the original drug（Cur）.Objective: The aim of this study was to study the cell uptake of Cur,CB and FE using the Caco-2 cells and the intestinal transport of Cur,CB and FE using an in vitro Caco-2 cell monolayer model.Methods: In this study,firstly,the cellular uptake of Cur,CB and FE in Caco-2 cells was investigated.Secondly,the Caco-2 cell monolayer model was established and its integrity and tightness were evaluated.Thirdly,the intestinal transport of Cur,CB and FE were investigated by the Caco-2 cell monolayer model.Then,the drugs’ amounts of transport was measured using HPLC method,and the apparent permeability coefficient(P_app)was calculated,the transport mechanism of CB and FE were speculated.Results: The results showed that:（1）In the cellular uptake experiment,the three compounds was varied with different concentrations and time intervals in the experimental concentration range,and exhibited concentration-and time-dependent uptake in cells.And the uptake amounts of Cur,CB and FE were 1.60 ± 0.15 nmol/mg protein,4.65 ± 0.23 nmol/mg protein and 6.64 ± 0.27 nmol/mg protein at 50 μM in 2 h,respectively.（2）The bi-directional transport of Cur,CB and FE in vitro model showed that the transport amounts of the drugs increased with time.The apparent permeability coefficient（AP→BL）indicating that CB(3.18 ± 0.31 × 10^-6 cm/s)and FE(5.28 ± 0.83 × 10^-6 cm/s)are higher than Cur(1.13 ± 0.11 × 10^-6 cm/s)in the same concentration（25 μM）.（3）The ER values of the three compounds were in the range of 1-1.5,suggesting that there was no active efflux involved in the transport process.（4）The transport of CB and FE exhibited concentration-dependent,indicated that the intestinal transport mechanism of the them were mainly passive transport.Conclusion: In summary,the results demonstrated that both the intestinal permeability of CB and FE across Caco-2 cell monolayers was significantly improved.Thus they might show a higher oral bioavailability in vivo,and show the potential application in clinical medication or nutraceutical.