UGT1A1 and UGT1A9 Are Responsible for Phase II Metabolism of Tectorigenin and Irigenin In Vitro
Tectorigenin and irigenin are biologically active isoflavones of <i>Belamcanda chinensis</i> (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 n...
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MDPI AG
2022-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/13/4104 |
| _version_ | 1797442564991746048 |
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| author | Ji Li Zhangyao Xu Jifeng Gu |
| author_facet | Ji Li Zhangyao Xu Jifeng Gu |
| author_sort | Ji Li |
| collection | DOAJ |
| description | Tectorigenin and irigenin are biologically active isoflavones of <i>Belamcanda chinensis</i> (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. |
| first_indexed | 2024-03-09T12:44:48Z |
| format | Article |
| id | doaj.art-562549eb85bb49ffabed700d7c24c666 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T12:44:48Z |
| publishDate | 2022-06-01 |
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| spelling | doaj.art-562549eb85bb49ffabed700d7c24c6662023-11-30T22:14:05ZengMDPI AGMolecules1420-30492022-06-012713410410.3390/molecules27134104UGT1A1 and UGT1A9 Are Responsible for Phase II Metabolism of Tectorigenin and Irigenin In VitroJi Li0Zhangyao Xu1Jifeng Gu2Department of Radiation Oncology, Eye and ENT Hospital, Fudan University, Shanghai 200031, ChinaDepartment of Pharmacy, Eye and ENT Hospital, Fudan University, Shanghai 200031, ChinaDepartment of Pharmacy, Eye and ENT Hospital, Fudan University, Shanghai 200031, ChinaTectorigenin and irigenin are biologically active isoflavones of <i>Belamcanda chinensis</i> (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.https://www.mdpi.com/1420-3049/27/13/4104tectorigeninirigeninglucuronidationhuman liver microsomesresponse factor method |
| spellingShingle | Ji Li Zhangyao Xu Jifeng Gu UGT1A1 and UGT1A9 Are Responsible for Phase II Metabolism of Tectorigenin and Irigenin In Vitro Molecules tectorigenin irigenin glucuronidation human liver microsomes response factor method |
| title | UGT1A1 and UGT1A9 Are Responsible for Phase II Metabolism of Tectorigenin and Irigenin In Vitro |
| title_full | UGT1A1 and UGT1A9 Are Responsible for Phase II Metabolism of Tectorigenin and Irigenin In Vitro |
| title_fullStr | UGT1A1 and UGT1A9 Are Responsible for Phase II Metabolism of Tectorigenin and Irigenin In Vitro |
| title_full_unstemmed | UGT1A1 and UGT1A9 Are Responsible for Phase II Metabolism of Tectorigenin and Irigenin In Vitro |
| title_short | UGT1A1 and UGT1A9 Are Responsible for Phase II Metabolism of Tectorigenin and Irigenin In Vitro |
| title_sort | ugt1a1 and ugt1a9 are responsible for phase ii metabolism of tectorigenin and irigenin in vitro |
| topic | tectorigenin irigenin glucuronidation human liver microsomes response factor method |
| url | https://www.mdpi.com/1420-3049/27/13/4104 |
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