Department of Radiation Oncology, Eye and ENT Hospital, Fudan University, Shanghai 200031, China.
Department of Pharmacy, Eye and ENT Hospital, Fudan University, Shanghai 200031, China.
Molecules. 2022 Jun 26;27(13):4104. doi: 10.3390/molecules27134104.
Tectorigenin and irigenin are biologically active isoflavones of (L.) DC. Previous studies indicated that both compounds could be metabolized in vivo; however, the kinetic parameters of enzymes involved in the metabolization of tectorigenin and irigenin have not been identified. The aim of this study was to investigate UGTs involved in the glucuronidation of tectorigenin and irigenin and determine enzyme kinetic parameters using pooled human liver microsomes (HLMs) and recombinant UGTs. Glucuronides of tectorigenin and irigenin were identified using high-performance liquid chromatography (HPLC) coupled with mass spectrometry and quantified by HPLC using a response factor method. The results showed that tectorigenin and irigenin were modified by glucuronidation in HLMs. One metabolite of tectorigenin (M) and two metabolites of irigenin (M1 and M2) were detected. Chemical inhibition and recombinant enzyme experiments revealed that several enzymes could catalyze tectorigenin and irigenin glucuronidation. Among them, UGT1A1 and UGT1A9 were the primary enzymes for both tectorigenin and irigenin; however, the former mostly produced irigenin glucuronide M1, while the latter mostly produced irigenin glucuronide M2. These findings suggest that UGT1A1 and UGT1A9 were the primary isoforms metabolizing tectorigenin and irigenin in HLMs, which could be involved in drug-drug interactions and, therefore, should be monitored in clinical practice.
染料木黄酮和毛蕊异黄酮是（L.）DC 的生物活性异黄酮。先前的研究表明，这两种化合物都可以在体内代谢；然而，参与染料木黄酮和毛蕊异黄酮代谢的酶的动力学参数尚未确定。本研究旨在研究参与染料木黄酮和毛蕊异黄酮葡萄糖醛酸化的 UGT，并使用人肝微粒体（HLM）和重组 UGT 来确定酶动力学参数。使用高效液相色谱（HPLC）-质谱联用技术鉴定染料木黄酮和毛蕊异黄酮的葡萄糖醛酸缀合物，并通过 HPLC 使用响应因子法进行定量。结果表明，染料木黄酮和毛蕊异黄酮在 HLMs 中通过葡萄糖醛酸化进行修饰。检测到染料木黄酮的一种代谢物（M）和毛蕊异黄酮的两种代谢物（M1 和 M2）。化学抑制和重组酶实验表明，几种酶可以催化染料木黄酮和毛蕊异黄酮的葡萄糖醛酸化。其中，UGT1A1 和 UGT1A9 是染料木黄酮和毛蕊异黄酮的主要酶；然而，前者主要产生毛蕊异黄酮葡萄糖醛酸 M1，而后者主要产生毛蕊异黄酮葡萄糖醛酸 M2。这些发现表明，UGT1A1 和 UGT1A9 是 HLMs 中代谢染料木黄酮和毛蕊异黄酮的主要同工酶，可能参与药物相互作用，因此在临床实践中应进行监测。
