The Role of ABC and SLC Transporters in the Pharmacokinetics of Dietary and Herbal Phytochemicals and their Interactions with Xenobiotics

Yan      Li; Jun      Lu; James      W. Paxton

doi:10.2174/1389200211209050624

Abstract

There is accumulating evidence that many compounds, known as phytochemicals (PCs), which are derived from dietary plants and herbs, may have a role in combating a number of chronic diseases. Despite many in vitro studies elucidating the mechanism(s) of action of various PCs, there are still reservations with regard to their health benefits in vivo, particularly as there is a paucity of research on their oral bioavailability, their pharmacokinetics, and the concentrations achieved at their site(s) of action. Recently various transporters, including the ATP-binding cassette (ABC) and the solute carrier (SLC) transporters, have been cloned and functional analyses have suggested that they play significant roles in the absorption and disposition of most drugs and PCs. While some SLC transporters facilitate absorption of PCs into the systemic circulation, various efflux pumps, including the ABC transporters, actively transport the PC back into the gastro-intestinal (GI) lumen, thus preventing further penetration into the body. Some ABC transporters also act in concert with Phase 1 and 2 metabolizing enzymes as a defensive barrier in the intestines and liver. If the PC overcomes the defence mechanisms of the gut and the liver, it will enter the systemic circulation and be distributed to the other organs of the body and possible site(s) of action. PCs can usually pass with ease through the pores of the capillaries of organs such as the heart and lungs, but with difficulty into pharmacological sanctuaries, such as the brain, testis, or foetus. Such sanctuaries contain a number of efflux transporters in their protective membrane, which restrict the penetration of xenobiotics, including PCs. The ABC and SLC transporters are also abundantly expressed in the liver and kidney and regulate the excretion of many compounds, including PCs and their metabolites. It is also becoming apparent that there is a complex interplay between various PCs and their ability to modulate the activity of these transporters involved in the processes of absorption, metabolism, distribution and excretion, which control the extent of xenobiotic exposure in the body. This review describes the importance of the ABC and SLC transporters in the pharmacokinetics of dietary and herbal PCs, and their interactions with other xenobiotics.

Keywords: ABC transporter, SLC transporter, Phytochemicals, Pharmacokinetics, Xenobiotics, Interactions, PCs, ATP-binding cassette, gastro-intestinal (GI) lumen, neurodegenerative diseases