Herb-drug interaction between Shaoyao-Gancao-Fuzi decoction and tofacitinib via CYP450 enzymes
Copyright © 2022 Elsevier B.V. All rights reserved..
ETHNOPHARMACOLOGY RELEVANCE: Shaoyao-Gancao-Fuzi decoction (SGFD), a well-known traditional Chinese medicine formula, was originally described in "Treatise on Febrile Diseases" and has been extensively used to dispel wind, eliminate dampness and treat paralysis. It is widely used for the treatment of rheumatoid arthritis in clinic. However, the effect of SGFD on the activity of cytochrome P450 enzymes (CYP450s) and the herb-drug interactions are rarely studied.
OBJECTIVE: The aim of this study was to investigate the effect of SGFD on the activity of CYP450s and evaluate the potential herb-drug interactions between SGFD and tofacitinib, commonly used disease-modifying antirheumatic drug in rheumatoid arthritis.
MATERIALS AND METHODS: The cocktail approach was employed to assess the effect of SGFD on the activity of CYP1A2, 3A4, 2A6, 2E1, and 2C9. The pharmacokinetic profile of oral administration of tofacitinib in rats after two weeks of treatment with SGFD was investigated. RT-qPCR and molecular docking were performed to unveil the underlying mechanism of the herb-drug interaction.
RESULTS: SGFD had no effect on the activities of CYP2E1 and 2C9, had a weak effect on CYP2A6, and had activatory effect on CYP1A2. However, it had a dramatically inhibitory effect on the activity of CYP3A4. Simultaneously, the values of Cmax and AUC0-∞ of tofacitinib were obviously increased after treatment with SGFD for 14 days. The mechanism study manifested that SGFD significantly reduced the gene transcription of CYP3A. Molecular docking work confirmed that the inhibitory activity of glycyrrhetinic acid, glycyrrhizic acid and liquiritin, the main ingredients of SGFD, occurred by occupying the active sites of CYP3A4 and by making favorable interactions with its key residues.
CONCLUSIONS: The system exposure of tofacitinib was increased by SGFD. SGFD could affect the activity and gene expression of the key metabolic enzyme CYP3A. These findings give a clear understanding to predict herb-drug interaction of SGFD for safe clinical use in future.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:295 |
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| Enthalten in: |
Journal of ethnopharmacology - 295(2022) vom: 15. Sept., Seite 115437 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lin, Li [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.06.2022 Date Revised 22.06.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jep.2022.115437 |
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| Förderinstitution / Projekttitel: |
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| 500 | |a Date Revised 22.06.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier B.V. All rights reserved. | ||
| 520 | |a ETHNOPHARMACOLOGY RELEVANCE: Shaoyao-Gancao-Fuzi decoction (SGFD), a well-known traditional Chinese medicine formula, was originally described in "Treatise on Febrile Diseases" and has been extensively used to dispel wind, eliminate dampness and treat paralysis. It is widely used for the treatment of rheumatoid arthritis in clinic. However, the effect of SGFD on the activity of cytochrome P450 enzymes (CYP450s) and the herb-drug interactions are rarely studied | ||
| 520 | |a OBJECTIVE: The aim of this study was to investigate the effect of SGFD on the activity of CYP450s and evaluate the potential herb-drug interactions between SGFD and tofacitinib, commonly used disease-modifying antirheumatic drug in rheumatoid arthritis | ||
| 520 | |a MATERIALS AND METHODS: The cocktail approach was employed to assess the effect of SGFD on the activity of CYP1A2, 3A4, 2A6, 2E1, and 2C9. The pharmacokinetic profile of oral administration of tofacitinib in rats after two weeks of treatment with SGFD was investigated. RT-qPCR and molecular docking were performed to unveil the underlying mechanism of the herb-drug interaction | ||
| 520 | |a RESULTS: SGFD had no effect on the activities of CYP2E1 and 2C9, had a weak effect on CYP2A6, and had activatory effect on CYP1A2. However, it had a dramatically inhibitory effect on the activity of CYP3A4. Simultaneously, the values of Cmax and AUC0-∞ of tofacitinib were obviously increased after treatment with SGFD for 14 days. The mechanism study manifested that SGFD significantly reduced the gene transcription of CYP3A. Molecular docking work confirmed that the inhibitory activity of glycyrrhetinic acid, glycyrrhizic acid and liquiritin, the main ingredients of SGFD, occurred by occupying the active sites of CYP3A4 and by making favorable interactions with its key residues | ||
| 520 | |a CONCLUSIONS: The system exposure of tofacitinib was increased by SGFD. SGFD could affect the activity and gene expression of the key metabolic enzyme CYP3A. These findings give a clear understanding to predict herb-drug interaction of SGFD for safe clinical use in future | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cytochrome P450 enzymes | |
| 650 | 4 | |a Herbal-drug interactions | |
| 650 | 4 | |a Molecular docking | |
| 650 | 4 | |a Shaoyao-Gancao-Fuzi decoction | |
| 650 | 4 | |a Tofacitinib | |
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| 650 | 7 | |a Drugs, Chinese Herbal |2 NLM | |
| 650 | 7 | |a Piperidines |2 NLM | |
| 650 | 7 | |a Pyrimidines |2 NLM | |
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| 650 | 7 | |a glycyrrhizae radix et rhizoma |2 NLM | |
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| 650 | 7 | |a Cytochrome P-450 CYP1A2 |2 NLM | |
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| 650 | 7 | |a Cytochrome P-450 CYP3A |2 NLM | |
| 650 | 7 | |a EC 1.14.14.1 |2 NLM | |
| 700 | 1 | |a Wang, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Shao, Sennan |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Yufeng |e verfasserin |4 aut | |
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