The roles of CYP2C19 and CYP3A4 in the in vitro metabolism of β‐eudesmol in human liver: Reaction phenotyping and enzyme kinetics
Abstract β‐eudesmol is a major bioactive component of Atractylodes lancea (AL). AL has been developed as the capsule formulation of standardized AL extract for treating cholangiocarcinoma (CCA). However, the complex constituents of herbal products increase the risk of adverse drug interactions. β‐eu...
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| Format: | Article |
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Wiley
2023-12-01
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| Series: | Pharmacology Research & Perspectives |
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| Online Access: | https://doi.org/10.1002/prp2.1149 |
| _version_ | 1797389575527596032 |
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| author | Nadda Muhamad Kesara Na‐Bangchang |
| author_facet | Nadda Muhamad Kesara Na‐Bangchang |
| author_sort | Nadda Muhamad |
| collection | DOAJ |
| description | Abstract β‐eudesmol is a major bioactive component of Atractylodes lancea (AL). AL has been developed as the capsule formulation of standardized AL extract for treating cholangiocarcinoma (CCA). However, the complex constituents of herbal products increase the risk of adverse drug interactions. β‐eudesmol has demonstrated inhibitory effects on rCYP2C19 and rCYP3A4 in the previous research. This study aimed to identify the cytochrome P450 (CYP) isoforms responsible for the metabolism of β‐eudesmol and determine the enzyme kinetic parameters and the metabolic stability of β‐eudesmol metabolism in the microsomal system. Reaction phenotyping using human recombinant CYPs (rCYPs) and selective chemical inhibitors of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 was performed, and enzyme kinetics and metabolic stability were investigated using human liver microsome (HLM). The results suggest that CYP2C19 and CYP3A4 play significant roles in β‐eudesmol metabolism. The disappearance half‐life (t1/2) and intrinsic clearance (CLint) of β‐eudesmol were 17.09 min and 0.20 mL/min·mg protein, respectively. Enzyme kinetic analysis revealed the Michaelis–Menten constant (Km) and maximum velocity (Vmax) of 16.76 μM and 3.35 nmol/min·mg protein, respectively. As a component of AL, β‐eudesmol, as a substrate and inhibitor of CYP2C19 and CYP3A4, has a high potential for drug–drug interactions when AL is co‐administered with other herbs or conventional medicines. |
| first_indexed | 2024-03-08T22:58:53Z |
| format | Article |
| id | doaj.art-c84c45f985864458a91a34146014c0fb |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-03-08T22:58:53Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-c84c45f985864458a91a34146014c0fb2023-12-16T03:52:31ZengWileyPharmacology Research & Perspectives2052-17072023-12-01116n/an/a10.1002/prp2.1149The roles of CYP2C19 and CYP3A4 in the in vitro metabolism of β‐eudesmol in human liver: Reaction phenotyping and enzyme kineticsNadda Muhamad0Kesara Na‐Bangchang1Graduate Studies, Chulabhorn International College of Medicine Thammasat University Pathumthani ThailandGraduate Studies, Chulabhorn International College of Medicine Thammasat University Pathumthani ThailandAbstract β‐eudesmol is a major bioactive component of Atractylodes lancea (AL). AL has been developed as the capsule formulation of standardized AL extract for treating cholangiocarcinoma (CCA). However, the complex constituents of herbal products increase the risk of adverse drug interactions. β‐eudesmol has demonstrated inhibitory effects on rCYP2C19 and rCYP3A4 in the previous research. This study aimed to identify the cytochrome P450 (CYP) isoforms responsible for the metabolism of β‐eudesmol and determine the enzyme kinetic parameters and the metabolic stability of β‐eudesmol metabolism in the microsomal system. Reaction phenotyping using human recombinant CYPs (rCYPs) and selective chemical inhibitors of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 was performed, and enzyme kinetics and metabolic stability were investigated using human liver microsome (HLM). The results suggest that CYP2C19 and CYP3A4 play significant roles in β‐eudesmol metabolism. The disappearance half‐life (t1/2) and intrinsic clearance (CLint) of β‐eudesmol were 17.09 min and 0.20 mL/min·mg protein, respectively. Enzyme kinetic analysis revealed the Michaelis–Menten constant (Km) and maximum velocity (Vmax) of 16.76 μM and 3.35 nmol/min·mg protein, respectively. As a component of AL, β‐eudesmol, as a substrate and inhibitor of CYP2C19 and CYP3A4, has a high potential for drug–drug interactions when AL is co‐administered with other herbs or conventional medicines.https://doi.org/10.1002/prp2.1149Atractylodes lancea (Thunb.) DCcytochrome P450drug metabolismenzyme kineticsreaction phenotypingβ‐eudesmol |
| spellingShingle | Nadda Muhamad Kesara Na‐Bangchang The roles of CYP2C19 and CYP3A4 in the in vitro metabolism of β‐eudesmol in human liver: Reaction phenotyping and enzyme kinetics Pharmacology Research & Perspectives Atractylodes lancea (Thunb.) DC cytochrome P450 drug metabolism enzyme kinetics reaction phenotyping β‐eudesmol |
| title | The roles of CYP2C19 and CYP3A4 in the in vitro metabolism of β‐eudesmol in human liver: Reaction phenotyping and enzyme kinetics |
| title_full | The roles of CYP2C19 and CYP3A4 in the in vitro metabolism of β‐eudesmol in human liver: Reaction phenotyping and enzyme kinetics |
| title_fullStr | The roles of CYP2C19 and CYP3A4 in the in vitro metabolism of β‐eudesmol in human liver: Reaction phenotyping and enzyme kinetics |
| title_full_unstemmed | The roles of CYP2C19 and CYP3A4 in the in vitro metabolism of β‐eudesmol in human liver: Reaction phenotyping and enzyme kinetics |
| title_short | The roles of CYP2C19 and CYP3A4 in the in vitro metabolism of β‐eudesmol in human liver: Reaction phenotyping and enzyme kinetics |
| title_sort | roles of cyp2c19 and cyp3a4 in the in vitro metabolism of β eudesmol in human liver reaction phenotyping and enzyme kinetics |
| topic | Atractylodes lancea (Thunb.) DC cytochrome P450 drug metabolism enzyme kinetics reaction phenotyping β‐eudesmol |
| url | https://doi.org/10.1002/prp2.1149 |
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