In vitro intestinal transport of phyllanthin across Caco-2 cell monolayers

Phyllanthin, a major bioactive lignan component of Phyllanthus amarus, possesses several therapeutic properties and is a potential candidate for combined treatment with conventional chemotherapies. The purposes of this study were to explore the processes of intestinal absorption and transport mechanisms of phyllanthin. Phyllanthin was isolated from Phyllanthus amarus leaves and purified to obtain a purity of more than 98 %. Caco-2 cell monolayers were used as an in vitro model of the human intestinal barrier. Bidirectional studies of phyllanthin across Caco-2 cell monolayers were performed to investigate the roles of active and passive mechanisms of phyllanthin intestinal transport. The transport mechanism of phyllanthin across Caco-2 cell monolayers was evaluated by comparing the permeability of phyllanthin under different conditions; i.e. the effects of phyllanthin concentration, opening of tight junctions and verapamil treatment. Phyllanthin was found to be absorbed in a concentration-dependent manner. The asymmetric concentration-permeability profile indicated that phyllanthin was transported across Caco-2 monolayers not only by simple passive diffusion but also by efflux transport. This study demonstrated for the first time that phyllanthin has a high permeability across Caco-2 cell monolayers, with the coexistence of paracellular, passive transcellular. and P-gp-mediated efflux pathways. All three approaches - the P-gp inhibition, increasing concentration and opening of tight junctions - may be used to improve the oral absorption of phyllanthin. This study shed new light on the mechanistic understanding of phyllanthin transport across the intestinal epithelium, and provided useful information for further research on phyllanthin.