Pharmacokinetic Herb-Drug Interactions of Xiang-Sha-Liu-Jun-Zi-Tang and Paclitaxel in Male Sprague Dawley Rats and Its Influence on Enzyme Kinetics in Human Liver Microsomes
Paclitaxel is a prescribed anticancer drug used to treat various cancers. It is a substrate of cytochrome P-450 (CYP-450) enzymes. Despite its efficacy, paclitaxel has severe side effects. Herbal medicines are commonly used to treat the side effects of chemotherapy. They can be administered before,...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.858007/full |
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| author | Alinafe Magret Kapelemera Yow-Shieng Uang Yow-Shieng Uang Li-Hsuan Wang Tien-Yuan Wu Fang-Yu Lee Li Tai Ching-Chiung Wang Ching-Chiung Wang Ching-Chiung Wang Ching-Chiung Wang Chia-Jung Lee Chia-Jung Lee Chia-Jung Lee |
| author_facet | Alinafe Magret Kapelemera Yow-Shieng Uang Yow-Shieng Uang Li-Hsuan Wang Tien-Yuan Wu Fang-Yu Lee Li Tai Ching-Chiung Wang Ching-Chiung Wang Ching-Chiung Wang Ching-Chiung Wang Chia-Jung Lee Chia-Jung Lee Chia-Jung Lee |
| author_sort | Alinafe Magret Kapelemera |
| collection | DOAJ |
| description | Paclitaxel is a prescribed anticancer drug used to treat various cancers. It is a substrate of cytochrome P-450 (CYP-450) enzymes. Despite its efficacy, paclitaxel has severe side effects. Herbal medicines are commonly used to treat the side effects of chemotherapy. They can be administered before, during, and after chemotherapy. Xiang-Sha-Liu-Jun-Zi Tang (XSLJZT) is a herbal formula commonly used in breast cancer patients. The main purpose of this study was to assess the pharmacokinetic (PK) influence of XSLJZT on paclitaxel PK parameters, determine its effect on CYP-450 enzyme expression, and evaluate its effect on enzyme activity. Sprague Dawley rats were classified into pretreatment and co-treatment groups, where XSLJZT was pre-administered for 3, 5, and 7 days and co-administered 2 h before paclitaxel administration. The rat liver tissues and Hep-G2 cells were used to determine the effects of XSLJZT on CYP3A1/2 and CYP3A4 enzymes respectively. Western blot analysis was used to detect changes in the CYP3A1/2 and CYP3A4 enzymes expression. The influence of XSLJZT on enzyme activity was evaluated using human liver microsomes, and a liquid chromatography-tandem mass spectrometric system was developed to monitor paclitaxel levels in rat plasma. Results demonstrated that XSLJZT increased the area under the concentration versus time curve (AUC) for paclitaxel in pretreatment groups by 2-, 3-, and 4-fold after 3, 5, and 7 days, respectively. In contrast, no significant change in the AUC was observed in the co-treatment group. However, the half-life was prolonged in all groups from 17.11 min to a maximum of 37.56 min. XSLJZT inhibited CYP3A1/2 expression in the rat liver tissues and CYP3A4 enzymes in Hep-G2 cells in a time-dependent manner, with the highest inhibition observed after 7 days of pretreatment in rat liver tissues. In the enzyme kinetics study, XSLJZT inhibited enzyme activity in a competitive dose-dependent manner. In conclusion, there is a potential interaction between XSLJZT and paclitaxel at different co-treatment and pretreatment time points. |
| first_indexed | 2024-04-13T10:19:36Z |
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| id | doaj.art-5b8946e3f5934a49b0e5a787b43ed7e1 |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T10:19:36Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-5b8946e3f5934a49b0e5a787b43ed7e12022-12-22T02:50:33ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-04-011310.3389/fphar.2022.858007858007Pharmacokinetic Herb-Drug Interactions of Xiang-Sha-Liu-Jun-Zi-Tang and Paclitaxel in Male Sprague Dawley Rats and Its Influence on Enzyme Kinetics in Human Liver MicrosomesAlinafe Magret Kapelemera0Yow-Shieng Uang1Yow-Shieng Uang2Li-Hsuan Wang3Tien-Yuan Wu4Fang-Yu Lee5Li Tai6Ching-Chiung Wang7Ching-Chiung Wang8Ching-Chiung Wang9Ching-Chiung Wang10Chia-Jung Lee11Chia-Jung Lee12Chia-Jung Lee13PhD Program in Clinical Drug Development of Herbal Medicine, Taipei Medical University, Taipei, TaiwanGraduate Institute of Pharmacognosy, Taipei Medical University, Taipei, TaiwanRosetta Pharmamate Co., Ltd, New Taipei City, TaiwanSchool of Pharmacy, Taipei Medical University, Taipei, TaiwanDepartment of Pharmacology, School of Medicine, College of Medicine, Tzu Chi University, Hualien, TaiwanGraduate Institute of Pharmacognosy, Taipei Medical University, Taipei, TaiwanRosetta Pharmamate Co., Ltd, New Taipei City, TaiwanPhD Program in Clinical Drug Development of Herbal Medicine, Taipei Medical University, Taipei, TaiwanGraduate Institute of Pharmacognosy, Taipei Medical University, Taipei, TaiwanSchool of Pharmacy, Taipei Medical University, Taipei, TaiwanTraditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, TaiwanPhD Program in Clinical Drug Development of Herbal Medicine, Taipei Medical University, Taipei, TaiwanGraduate Institute of Pharmacognosy, Taipei Medical University, Taipei, TaiwanTraditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, TaiwanPaclitaxel is a prescribed anticancer drug used to treat various cancers. It is a substrate of cytochrome P-450 (CYP-450) enzymes. Despite its efficacy, paclitaxel has severe side effects. Herbal medicines are commonly used to treat the side effects of chemotherapy. They can be administered before, during, and after chemotherapy. Xiang-Sha-Liu-Jun-Zi Tang (XSLJZT) is a herbal formula commonly used in breast cancer patients. The main purpose of this study was to assess the pharmacokinetic (PK) influence of XSLJZT on paclitaxel PK parameters, determine its effect on CYP-450 enzyme expression, and evaluate its effect on enzyme activity. Sprague Dawley rats were classified into pretreatment and co-treatment groups, where XSLJZT was pre-administered for 3, 5, and 7 days and co-administered 2 h before paclitaxel administration. The rat liver tissues and Hep-G2 cells were used to determine the effects of XSLJZT on CYP3A1/2 and CYP3A4 enzymes respectively. Western blot analysis was used to detect changes in the CYP3A1/2 and CYP3A4 enzymes expression. The influence of XSLJZT on enzyme activity was evaluated using human liver microsomes, and a liquid chromatography-tandem mass spectrometric system was developed to monitor paclitaxel levels in rat plasma. Results demonstrated that XSLJZT increased the area under the concentration versus time curve (AUC) for paclitaxel in pretreatment groups by 2-, 3-, and 4-fold after 3, 5, and 7 days, respectively. In contrast, no significant change in the AUC was observed in the co-treatment group. However, the half-life was prolonged in all groups from 17.11 min to a maximum of 37.56 min. XSLJZT inhibited CYP3A1/2 expression in the rat liver tissues and CYP3A4 enzymes in Hep-G2 cells in a time-dependent manner, with the highest inhibition observed after 7 days of pretreatment in rat liver tissues. In the enzyme kinetics study, XSLJZT inhibited enzyme activity in a competitive dose-dependent manner. In conclusion, there is a potential interaction between XSLJZT and paclitaxel at different co-treatment and pretreatment time points.https://www.frontiersin.org/articles/10.3389/fphar.2022.858007/fulltraditional Chinese medicine formulaXiang-Sha-Liu-Jun-Zi tangpaclitaxelpharmacokineticsenzyme kinetics |
| spellingShingle | Alinafe Magret Kapelemera Yow-Shieng Uang Yow-Shieng Uang Li-Hsuan Wang Tien-Yuan Wu Fang-Yu Lee Li Tai Ching-Chiung Wang Ching-Chiung Wang Ching-Chiung Wang Ching-Chiung Wang Chia-Jung Lee Chia-Jung Lee Chia-Jung Lee Pharmacokinetic Herb-Drug Interactions of Xiang-Sha-Liu-Jun-Zi-Tang and Paclitaxel in Male Sprague Dawley Rats and Its Influence on Enzyme Kinetics in Human Liver Microsomes Frontiers in Pharmacology traditional Chinese medicine formula Xiang-Sha-Liu-Jun-Zi tang paclitaxel pharmacokinetics enzyme kinetics |
| title | Pharmacokinetic Herb-Drug Interactions of Xiang-Sha-Liu-Jun-Zi-Tang and Paclitaxel in Male Sprague Dawley Rats and Its Influence on Enzyme Kinetics in Human Liver Microsomes |
| title_full | Pharmacokinetic Herb-Drug Interactions of Xiang-Sha-Liu-Jun-Zi-Tang and Paclitaxel in Male Sprague Dawley Rats and Its Influence on Enzyme Kinetics in Human Liver Microsomes |
| title_fullStr | Pharmacokinetic Herb-Drug Interactions of Xiang-Sha-Liu-Jun-Zi-Tang and Paclitaxel in Male Sprague Dawley Rats and Its Influence on Enzyme Kinetics in Human Liver Microsomes |
| title_full_unstemmed | Pharmacokinetic Herb-Drug Interactions of Xiang-Sha-Liu-Jun-Zi-Tang and Paclitaxel in Male Sprague Dawley Rats and Its Influence on Enzyme Kinetics in Human Liver Microsomes |
| title_short | Pharmacokinetic Herb-Drug Interactions of Xiang-Sha-Liu-Jun-Zi-Tang and Paclitaxel in Male Sprague Dawley Rats and Its Influence on Enzyme Kinetics in Human Liver Microsomes |
| title_sort | pharmacokinetic herb drug interactions of xiang sha liu jun zi tang and paclitaxel in male sprague dawley rats and its influence on enzyme kinetics in human liver microsomes |
| topic | traditional Chinese medicine formula Xiang-Sha-Liu-Jun-Zi tang paclitaxel pharmacokinetics enzyme kinetics |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.858007/full |
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