Department of Pharmacology & Clinical Pharmacology, School of Medical Sciences, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Curr Drug Metab. 2012 Jun 1;13(5):624-39. doi: 10.2174/1389200211209050624.
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.
越来越多的证据表明，许多化合物，被称为植物化学物质（PCs），它们来自于饮食中的植物和草药，可能在对抗许多慢性疾病方面发挥作用。尽管有许多体外研究阐明了各种 PCs 的作用机制，但对于它们在体内的健康益处仍存在保留意见，特别是因为对它们的口服生物利用度、药代动力学以及在作用部位达到的浓度的研究很少。最近，各种转运蛋白，包括 ATP 结合盒（ABC）和溶质载体（SLC）转运蛋白，已经被克隆，功能分析表明它们在大多数药物和 PCs 的吸收和处置中发挥重要作用。虽然一些 SLC 转运蛋白促进 PCs 进入全身循环，但各种外排泵，包括 ABC 转运蛋白，积极地将 PC 回送到胃肠道（GI）腔中，从而防止进一步渗透到体内。一些 ABC 转运蛋白还与 1 期和 2 期代谢酶一起作为肠道和肝脏中的防御屏障。如果 PC 克服了肠道和肝脏的防御机制，它将进入全身循环，并分布到身体的其他器官和可能的作用部位。PCs 通常可以轻松地穿过心脏和肺部等器官的毛细血管孔，但很难进入药理学庇护所，如大脑、睾丸或胎儿。这些庇护所的保护性膜中含有许多外排转运蛋白，限制了包括 PCs 在内的外源性物质的渗透。ABC 和 SLC 转运蛋白也在肝脏和肾脏中大量表达，调节许多化合物的排泄，包括 PCs 和它们的代谢物。越来越明显的是，各种 PCs 之间存在着复杂的相互作用，以及它们调节参与吸收、代谢、分布和排泄过程的这些转运蛋白的活性的能力，这些过程控制着体内外源性物质暴露的程度。本综述描述了 ABC 和 SLC 转运蛋白在饮食和草药 PCs 的药代动力学中的重要性，以及它们与其他外源性物质的相互作用。
