Foster B C, Vandenhoek S, Hana J, Krantis A, Akhtar M H, Bryan M, Budzinski J W, Ramputh A, Arnason J T
Office of Science, Therapeutic Products Directorate, Health Canada, Ottawa, Ontario, Canada.
Phytomedicine. 2003 May;10(4):334-42. doi: 10.1078/094471103322004839.
Spices, herbal and black teas, and soybean products were analyzed for their capacity to inhibit in vitro metabolism of drug marker substrates by human cytochrome P-450 (CYP) isoforms. Inhibition of drug metabolism was determined using aliquots or infusions from these products in a fluorescence-detection assay. Aliquots and infusions of all natural product categories inhibited 3A4 metabolism to some extent. Of the 26 aliquots from teas and spices further tested with 2C9, 2C19 and 2D6, many demonstrated significant inhibitory activity on the metabolism mediated by these isoforms. Black teas and herbal tea mixtures were generally more inhibitory than single-entity herbal teas. Spices and single-entity herbal teas showed species-specific isoform inhibition with sage, thyme, cloves, St John's Wort and goldenseal having the highest activity against several isoforms. Seven soybean varieties tested, as well as daidzein and genistein isolated from soybean, were found to inhibit 3A4-mediated metabolism. Genistein was found to inhibit 3A7- but not 3A5-mediated metabolism of the marker substrate. Assessment of the in vitro CYP inhibition potential for these natural products has important implications for predicting the likelihood of natural product-drug interactions if these products are taken concomitantly.
对香料、花草茶和红茶以及大豆制品进行了分析，以研究它们抑制人细胞色素P-450（CYP）同工酶体外代谢药物标记底物的能力。在荧光检测试验中，使用这些产品的等分试样或提取物来测定药物代谢的抑制情况。所有天然产品类别的等分试样和提取物都在一定程度上抑制了3A4代谢。在对茶叶和香料的26个等分试样进一步用2C9、2C19和2D6进行测试时，许多试样对这些同工酶介导的代谢表现出显著的抑制活性。红茶和花草茶混合物通常比单一花草茶的抑制作用更强。香料和单一花草茶表现出物种特异性的同工酶抑制作用，鼠尾草、百里香、丁香、圣约翰草和白毛茛对几种同工酶具有最高的活性。测试的7个大豆品种以及从大豆中分离出的大豆苷元和染料木黄酮均被发现抑制3A4介导的代谢。染料木黄酮被发现抑制标记底物的3A7介导的代谢，但不抑制3A5介导的代谢。评估这些天然产品的体外CYP抑制潜力对于预测这些产品与药物同时服用时发生天然产品-药物相互作用的可能性具有重要意义。
