The mechanism of intestinal absorption of nobiletin (NBL) was investigated using Caco-2 cells. The uptake of NBL from the apical membranes of Caco-2 cells was rapid and temperature-dependent and the presence of metabolic inhibitors, NaN3 and carbonylcyanide p-trifluoromethoxyphenylhydrazone, did not cause a decrease in NBL uptake. The relationship between the initial uptake of NBL and its concentration was saturable, suggesting the involvement of a carrier-mediated process. The K-m and uptake clearance (V-max/K-m) values for NBL were 50.6 and 168.1 mu l/mg protein/min, respectively. This clearance value was about 9-fold greater than that of the non-saturable uptake clearance (K-d: 18.5 mu l/ mg protein/min). The presence of structurally similar compounds, such as quercetin and luteolin, competitively inhibited NBL uptake. These results suggest that uptake of NBL from the apical membranes of Caco-2 cells is mainly mediated by an energy-independent facilitated diffusion process. (C) 2013 Elsevier Ltd. All rights reserved.