Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas, USA.
Sci Rep. 2016 Jun 22;6:28482. doi: 10.1038/srep28482.
Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), a natural naphthoquinone compound isolated from roots of Plumbago zeylanica L., has drawn a lot of attention for its plenty of pharmacological properties including antidiabetes and anti-cancer. The aim of this study was to investigate the effects of plumbagin on CYP1A2, CYP2B1/6, CYP2C9/11, CYP2D1/6, CYP2E1 and CYP3A2/4 activities in human and rat liver and evaluate the potential herb-drug interactions using the cocktail approach. All CYP substrates and their metabolites were analyzed using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plumbagin presented non-time-dependent inhibition of CYP activities in both human and rat liver. In humans, plumbagin was not only a mixed inhibitor of CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4, but also a non-competitive inhibitor of CYP1A2, with Ki values no more than 2.16 μM. In rats, the mixed inhibition of CYP1A2 and CYP2D1, and competitive inhibition for CYP2B1, CYP2C11 and CYP2E1 with Ki values less than 9.93 μM were observed. In general, the relatively low Ki values of plumbagin in humans would have a high potential to cause the toxicity and drug interactions involving CYP enzymes.
白花丹素（5-羟基-2-甲基-1,4-萘醌），一种从白花丹根部分离得到的天然萘醌化合物，因其丰富的药理特性而备受关注，包括抗糖尿病和抗癌作用。本研究旨在探讨白花丹素对人肝和鼠肝中 CYP1A2、CYP2B1/6、CYP2C9/11、CYP2D1/6、CYP2E1 和 CYP3A2/4 活性的影响，并采用鸡尾酒法评估其潜在的草药-药物相互作用。使用高效液相色谱-串联质谱法（LC-MS/MS）分析所有 CYP 底物及其代谢物。白花丹素在人肝和鼠肝中均呈现非时间依赖性 CYP 活性抑制。在人体内，白花丹素不仅是 CYP2B6、CYP2C9、CYP2D6、CYP2E1 和 CYP3A4 的混合抑制剂，也是 CYP1A2 的非竞争性抑制剂，Ki 值不超过 2.16 μM。在大鼠中，观察到对 CYP1A2 和 CYP2D1 的混合抑制，以及对 CYP2B1、CYP2C11 和 CYP2E1 的竞争性抑制，Ki 值均小于 9.93 μM。总的来说，白花丹素在人体内较低的 Ki 值表明其具有较高的引起涉及 CYP 酶的毒性和药物相互作用的潜力。
