Tan Shengnan, Dong Zhimin, Zhang Jiashuo, Efferth Thomas, Fu Yujie, Hua Xin
Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, 150040, Harbin, PR China.
Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, 150040, Harbin, PR China.
Biomed Chromatogr. 2017 Jun;31(6). doi: 10.1002/bmc.3888. Epub 2017 Jan 22.
Pinostrobin (PI, 5-hydroxy-7-methoxyflavanone) is a natural flavonoid known for its rich pharmacological activities. The objective of this study was to identify the human liver cytochrome P450 (CYP450) isoenzymes involved in the metabolism of PI. A single hydoxylated metabolite was obtained from PI after an incubation with pooled human liver microsomes (HLMs). The relative contributions of different CYP450s were evaluated using CYP450-selective inhibitors in HLMs and recombinant human CYP450 enzymes, and the results revealed the major involvement of CYP1A2, CYP2C9 and CYP2E1 in PI metabolism. We also evaluated the ability of PI to inhibit and induce human cytochrome P450 enzymes in vitro. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry analytical techniques were used to estimate the enzymatic activities of seven drug-metabolizing CYP450 isozymes in vitro. In HLMs, PI did not inhibit CYP 1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 (IC > 100 μm). In the induction studies, PI had minimal effects on CYP1A2, CYP2B6and CYP3A4 activity. Based on these results, PI would not be expected to cause clinically significant CYP450 inhibition or induction.
松属素（PI，5-羟基-7-甲氧基黄酮）是一种天然黄酮类化合物，以其丰富的药理活性而闻名。本研究的目的是确定参与PI代谢的人肝细胞色素P450（CYP450）同工酶。将PI与混合人肝微粒体（HLM）孵育后，得到了一种单一的羟基化代谢物。使用CYP450选择性抑制剂在HLM和重组人CYP450酶中评估了不同CYP450的相对贡献，结果表明CYP1A2、CYP2C9和CYP2E1主要参与PI代谢。我们还在体外评估了PI抑制和诱导人细胞色素P450酶的能力。采用高效液相色谱和液相色谱-串联质谱分析技术在体外估计7种药物代谢CYP450同工酶的酶活性。在HLM中，PI不抑制CYP 1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6或CYP3A4（IC＞100μm）。在诱导研究中，PI对CYP1A2、CYP2B6和CYP3A4活性的影响最小。基于这些结果，预计PI不会引起临床上显著的CYP450抑制或诱导。
