Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Department of Thoracic Surgery and Lung Transplant Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
J Pharm Biomed Anal. 2021 Sep 5;203:114222. doi: 10.1016/j.jpba.2021.114222. Epub 2021 Jun 24.
Irisflorentin is one of the bioactive constituents from the root of Belamcanda chinensis (L.) DC, which displayed anti-inflammatory and anti-tumor activities. In this work, the in vitro metabolism of irisflorentin was investigated using liver microsomes and hepatocytes. The metabolites were identified by ultra-high performance liquid chromatography combined with quadrupole/orbitrap tandem mass spectrometry. Under the current conditions, a total of 11 metabolites were detected and structurally identified according to accurate masses, fragment ions and retention times. Metabolite M10, identified as 6,7-dihydroxy-5,3',4',5'-tetramethoxy isoflavone, was biosynthesized and unambiguously characterized by nuclear magnetic resonance spectroscopy. The metabolic pathways of irisflorentin included oxidation, demethylation and glucuronidation. M10 was the most abundant metabolite in all tested species. Further phenotyping studies revealed that α-naphthoflavone and ketoconazole displayed significant inhibitory effect on the formation of M10. Cytochrome P450 (CYP) 1A2 and 3A4 were the major enzymes responsible for the formation of M10 by using individual recombinant human CYP450 enzymes. For the first time the current study provides an overview of the in vitro metabolic fates of irisflorentin, which is helpful for us to predict the human metabolism and the potential drug-drug interactions caused by irisflorentin.
鸢尾黄素是射干（Belamcanda chinensis（L.）DC）根中的一种生物活性成分，具有抗炎和抗肿瘤活性。在这项工作中，使用肝微粒体和肝细胞研究了鸢尾黄素的体外代谢。通过超高效液相色谱-四极杆/轨道阱串联质谱联用技术鉴定了代谢物。在当前条件下，根据准确质量、碎片离子和保留时间共检测到并结构鉴定出 11 种代谢物。代谢物 M10 被鉴定为 6,7-二羟基-5,3',4',5'-四甲氧基异黄酮，通过核磁共振波谱法进行了生物合成和明确表征。鸢尾黄素的代谢途径包括氧化、去甲基化和葡萄糖醛酸化。M10 是所有测试物种中含量最丰富的代谢物。进一步的表型研究表明，α-萘黄酮和酮康唑对 M10 的形成具有显著的抑制作用。使用单个重组人 CYP450 酶，细胞色素 P450（CYP）1A2 和 3A4 是形成 M10 的主要酶。本研究首次全面概述了鸢尾黄素的体外代谢命运，有助于我们预测鸢尾黄素的人体代谢和潜在的药物相互作用。
