The absorption characteristics of artepillin C (AC), an active ingredient of Brazilian propolis, were examined by measuring permeation across Caco-2 cell monolayers. The permeation rate in the basolateral-to-apical direction, J(bl-->ap), in the presence of proton gradient was 0.14 nmol/min/mg protein, whereas J(bl-->ap) in the absence of proton gradient was 1.14 nmol/min/mg protein. The latter value is nearly the same as the permeation rate in the apical-to-basolateral direction, J(ap-->bl), both in the presence and absence of proton gradient. In the presence of proton gradient, J(ap-->bl) was almost constant, irrespective of NaN(3) or benzoic acid. However, J(bl-->ap) dramatically increased upon the addition of NaN(3) or benzoic acid specifically to the apical side. In both the presence and absence of proton gradient, J(ap-->bl) also appeared to be constant irrespective of the paracellular permeability of Caco-2 cells. After AC was loaded apically in the presence of proton gradient, the intracellular AC increased with time. This accumulation was inhibited by apically loaded NaN(3). These indicate that AC transport occurs mainly via transcellular passive diffusion, although a considerable amount of AC was taken up intracellularly by monocarboxylic acid transporter (MCT) on the apical side and not transported out across the basolateral membrane, suggesting that different subtypes of MCT are involved.