Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes
Curcumin and germacrone, natural products present in the Zingiberaceae family of plants, have several biological properties. Among these properties, the anti-NSCLC cancer action is noteworthy. In this paper, kinetics of the two compounds in rat liver microsomes (RLMs), human liver microsomes (HLMs),...
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MDPI AG
2022-07-01
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| Series: | Molecules |
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| author | Shaofeng Su Hongxian Wu Jingfan Zhou Guangwei Yuan Haibo Wang Jie Feng |
| author_facet | Shaofeng Su Hongxian Wu Jingfan Zhou Guangwei Yuan Haibo Wang Jie Feng |
| author_sort | Shaofeng Su |
| collection | DOAJ |
| description | Curcumin and germacrone, natural products present in the Zingiberaceae family of plants, have several biological properties. Among these properties, the anti-NSCLC cancer action is noteworthy. In this paper, kinetics of the two compounds in rat liver microsomes (RLMs), human liver microsomes (HLMs), and cytochrome P450 (CYP) enzymes (CYP3A4, 1A2, 2E1, and 2C19) in an NADPH-generating system in vitro were evaluated by UP-HPLC–MS/MS (ultrahigh-pressure liquid chromatography–tandem mass spectrometry). The contents of four cytochrome P450 (CYP) enzymes, adjusting by the compounds were detected using Western blotting in vitro and in vivo. The t<sub>1/2</sub> of curcumin was 22.35 min in RLMs and 173.28 min in HLMs, while 18.02 and 16.37 min were gained for germacrone. The V<sub>max</sub> of curcumin in RLMs was about 4-fold in HLMs, meanwhile, the V<sub>max</sub> of germacrone in RLMs was similar to that of HLMs. The single enzyme t1/2 of curcumin was 38.51 min in CYP3A4, 301.4 min in 1A2, 69.31 min in 2E1, 63.01 min in 2C19; besides, as to the same enzymes, t1/2 of germacrone was 36.48 min, 86.64 min, 69.31 min, and 57.76 min. The dynamic curves were obtained by reasonable experimental design and the metabolism of curcumin and germacrone were selected in RLMs/HLMs. The selectivities in the two liver microsomes differed in degradation performance. These results meant that we should pay more attention to drugs in clinical medication–drug and drug–enzyme interactions. |
| first_indexed | 2024-03-09T06:08:40Z |
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| language | English |
| last_indexed | 2024-03-09T06:08:40Z |
| publishDate | 2022-07-01 |
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| series | Molecules |
| spelling | doaj.art-a8c9405be92c43c5b72abb798e1a53502023-12-03T12:01:36ZengMDPI AGMolecules1420-30492022-07-012714448210.3390/molecules27144482Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP EnzymesShaofeng Su0Hongxian Wu1Jingfan Zhou2Guangwei Yuan3Haibo Wang4Jie Feng5School of Pharmaceutical Sciences, Guangxi Medical University, Nanning 530021, ChinaSchool of Pharmaceutical Sciences, Guangxi Medical University, Nanning 530021, ChinaSchool of Pharmaceutical Sciences, Guangxi Medical University, Nanning 530021, ChinaGuangxi-ASEAN Food Inspection and Testing Center, Nanning 530029, ChinaGuangxi-ASEAN Food Inspection and Testing Center, Nanning 530029, ChinaSchool of Pharmaceutical Sciences, Guangxi Medical University, Nanning 530021, ChinaCurcumin and germacrone, natural products present in the Zingiberaceae family of plants, have several biological properties. Among these properties, the anti-NSCLC cancer action is noteworthy. In this paper, kinetics of the two compounds in rat liver microsomes (RLMs), human liver microsomes (HLMs), and cytochrome P450 (CYP) enzymes (CYP3A4, 1A2, 2E1, and 2C19) in an NADPH-generating system in vitro were evaluated by UP-HPLC–MS/MS (ultrahigh-pressure liquid chromatography–tandem mass spectrometry). The contents of four cytochrome P450 (CYP) enzymes, adjusting by the compounds were detected using Western blotting in vitro and in vivo. The t<sub>1/2</sub> of curcumin was 22.35 min in RLMs and 173.28 min in HLMs, while 18.02 and 16.37 min were gained for germacrone. The V<sub>max</sub> of curcumin in RLMs was about 4-fold in HLMs, meanwhile, the V<sub>max</sub> of germacrone in RLMs was similar to that of HLMs. The single enzyme t1/2 of curcumin was 38.51 min in CYP3A4, 301.4 min in 1A2, 69.31 min in 2E1, 63.01 min in 2C19; besides, as to the same enzymes, t1/2 of germacrone was 36.48 min, 86.64 min, 69.31 min, and 57.76 min. The dynamic curves were obtained by reasonable experimental design and the metabolism of curcumin and germacrone were selected in RLMs/HLMs. The selectivities in the two liver microsomes differed in degradation performance. These results meant that we should pay more attention to drugs in clinical medication–drug and drug–enzyme interactions.https://www.mdpi.com/1420-3049/27/14/4482cytochrome P450 enzymesUPLC–MS/MScurcumingermacronedrug–drug interaction |
| spellingShingle | Shaofeng Su Hongxian Wu Jingfan Zhou Guangwei Yuan Haibo Wang Jie Feng Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes Molecules cytochrome P450 enzymes UPLC–MS/MS curcumin germacrone drug–drug interaction |
| title | Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes |
| title_full | Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes |
| title_fullStr | Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes |
| title_full_unstemmed | Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes |
| title_short | Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes |
| title_sort | kinetic characteristics of curcumin and germacrone in rat and human liver microsomes involvement of cyp enzymes |
| topic | cytochrome P450 enzymes UPLC–MS/MS curcumin germacrone drug–drug interaction |
| url | https://www.mdpi.com/1420-3049/27/14/4482 |
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