[{"id":129,"uid":"NPDI-PSB8Vg","name":"Evaluation of selected Malaysian medicinal plants on phase I drug metabolizing enzymes, CYP2C9, CYP2D6 and CYP3A4 activities in vitro","napdiIdentifier":null,"overallSummary":"This study investigated the effects of selected Malaysian medicinal plant extracts towards human recombinant cytochrome P450 (CYP450) enzyme activities in vitro. Five Malaysian medicinal plants were tested on the three main CYP450 enzyme activities of CYP2C9, CYP2D6 and CYP3A4. The abilities of these extracts to inhibit human cytochrome P450 enzyme activities were analyzed using a luminescent assay. Orthosiphon stamineus showed the most potent inhibitory activity against CYP2C9 with an apparent IC<sub>50</sub> value of 77.5±1.1 μg mL<sup>-1</sup>, while Andrographis paniculata, Curcuma xanthorrhiza, Eurycoma longifolia and Mitragyna speciosa extracts showed negligible inhibition. On the metabolism mediated by CYP2D6, Mitragyna speciosa showed the most potent inhibitory activities with IC<sub>50</sub> values of 3.6±0.1 μg mL<sup>-1</sup>, followed by Orthosiphon stamineus, Andrographis paniculata and Curcuma xanthorrhiza with IC<sub>50</sub> value of 11.7±1.1, 44.2±4.5 and 215.3±71.6 fig mL<sup>-1</sup>, respectively. Andrographis paniculata ethanolic extract gave the lowest IC<sub>50</sub> value towards CYP3A4 with an apparent IC<sub>50</sub> value of 27.6±3.7 μg mL<sup>-1</sup>, followed by Orthosiphon stamineus (78.4±20.3 μg mL<sup>-1</sup>), Mitragyna speciosa (142.8±13.8 μg mL<sup>-1</sup>) and Curcuma xanthorrhiza (285.3±61.7 μg mL<sup>-1</sup>). Sulfaphenazole, quinidine and ketoconazole were used as positive controls for CYP2C9, CYP2D6 and CYP3A4 respectively. The findings suggest that Orthosiphon stamineus, Mitragyna speciosa and Andrographis paniculata may contribute to herb-drug interactions if they are administered concomitantly with drugs metabolized by CYP2C9, CYP2D6 and CYP3A4 respectively.","pubmedId":null,"embaseId":2010444809,"croIdentifier":"Universiti Sains Malaysia, Penang, Malaysia","croInformation":"Centre for Drug Research","dateStart":"2009-05-01T00:00:00.000Z","dateEnd":"2010-02-28T00:00:00.000Z","internalComment":null,"status":"published","compoundId":null,"naturalProductUid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","naturalProductSampleId":null,"studySourceTypeId":1,"naturalProduct":{"uid":"NP-00ed1235-cbd8-4117-85df-298b8b3cdcad","binomial":"Mitragyna speciosa","name":"Kratom","itis":null,"srs":"d469b67d-e9a6-459f-b209-c59451936336","source_id":"","conceptId":null},"compound":null,"studySourceType":{"id":1,"name":"Published report"},"experiments":[{"id":602,"uid":"NPDI-jkwBEg","name":"Inhibition of CYP2C9 by M. speciosa methanolic extract","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"Not specified.","croIdentifier":null,"comment":null,"experimentalConditionsComment":"M. speciosa methanolic extract was prepared in-house from the leaves of the plant. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.<br /><br />The minus-P450 wells (using luciferin-free water) were negative controls.","resultsComment":"IC50 not determined due to the less than 50% of inhibition.<br /><br />% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 1d. In some cases, SEM could not be estimated from the provided figure. <br /><br />0.01 µg/mL: 20 ± Unknown%<br />0.1 µg/mL: 18 ± Unknown%<br />1 µg/mL: 22 ± 6%<br />10 µg/mL: 23 ± 6%<br />100 µg/mL: 26 ± 2%<br />1000 µg/mL: See above data","internalComment":null,"objectCompoundId":193,"objectMetaboliteCompoundId":194,"precipitantCompoundId":182,"cytochromeB5Id":4,"studyId":129,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":1,"name":"In Vitro Enzyme Inhibition","isInVitro":true,"isTransporter":false,"isEnzyme":true,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000058"},"objectCompound":{"id":193,"name":"6’deoxyluciferin (luciferin h)","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":182,"name":"methanolic extract of kratom","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":"Often refers to the leaves of M. speciosa","conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":194,"name":"luciferin","unii":null,"inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","publicDescription":null,"internalComment":"AKA d-luciferin","conceptId":null,"enantiomerOfId":null},"enzymes":[{"id":8,"name":"CYP2C9","conceptId":4309227,"experiment_enzyme_xref":{"enzymeId":8,"experimentId":602}}],"transporters":[],"quantifiedMetabolites":[]},{"id":603,"uid":"NPDI-gWxQZg","name":"Inhibition of CYP2D6 by M. speciosa methanolic extract","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"Not specified.","croIdentifier":null,"comment":null,"experimentalConditionsComment":"M. speciosa methanolic extract was prepared in-house from the leaves of the plant. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.<br /><br />The minus-P450 wells (using luciferin-free water) were negative controls.","resultsComment":"% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 1d. In some cases, SEM could not be estimated from the provided figure. <br /><br />0.01 µg/mL: 25 ± Unknown%<br />0.1 µg/mL: 21 ± Unknown%<br />1 µg/mL: 35 ± 1%<br />10 µg/mL: 78 ± 0%<br />100 µg/mL: 91 ± 3%<br />1000 µg/mL: See above data","internalComment":null,"objectCompoundId":195,"objectMetaboliteCompoundId":194,"precipitantCompoundId":182,"cytochromeB5Id":4,"studyId":129,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":1,"name":"In Vitro Enzyme Inhibition","isInVitro":true,"isTransporter":false,"isEnzyme":true,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000058"},"objectCompound":{"id":195,"name":"ethylene glycol ester of luciferin 6’methyl ether (luciferin me-ege)","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":182,"name":"methanolic extract of kratom","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":"Often refers to the leaves of M. speciosa","conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":194,"name":"luciferin","unii":null,"inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","publicDescription":null,"internalComment":"AKA d-luciferin","conceptId":null,"enantiomerOfId":null},"enzymes":[{"id":10,"name":"CYP2D6","conceptId":4173631,"experiment_enzyme_xref":{"enzymeId":10,"experimentId":603}}],"transporters":[],"quantifiedMetabolites":[]},{"id":604,"uid":"NPDI-Df2Xyw","name":"Negligible inhibition of CYP3A4 by M. speciosa methanolic extract","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>Not specified.</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"M. speciosa methanolic extract was prepared in-house from the leaves of the plant. This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.<br /><br />The minus-P450 wells (using luciferin-free water) were negative controls.","resultsComment":"% enzyme inhibition versus precipitant concentration:<br />Values estimated from Figure 1d. In some cases, SEM could not be estimated from the provided figure. <br /><br />0.01 µg/mL: 18 ± Unknown%<br />0.1 µg/mL: 11 ± 4%<br />1 µg/mL: 9± 0%<br />10 µg/mL: 18 ± 4%<br />100 µg/mL: 50 ± 3%<br />1000 µg/mL: See above data","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":182,"cytochromeB5Id":4,"studyId":129,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":1,"name":"In Vitro Enzyme Inhibition","isInVitro":true,"isTransporter":false,"isEnzyme":true,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000058"},"objectCompound":{"id":196,"name":"luciferin 6’benzyl ether (luciferin-be)","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":182,"name":"methanolic extract of kratom","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":"Often refers to the leaves of M. speciosa","conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":194,"name":"luciferin","unii":null,"inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","publicDescription":null,"internalComment":"AKA d-luciferin","conceptId":null,"enantiomerOfId":null},"enzymes":[{"id":13,"name":"CYP3A4","conceptId":4306811,"experiment_enzyme_xref":{"enzymeId":13,"experimentId":604}}],"transporters":[],"quantifiedMetabolites":[]},{"id":605,"uid":"NPDI-H6ZqbA","name":"POS. CONTROL: Inhibition of CYP2C9 by sulfaphenazole","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"Not specified.","croIdentifier":null,"comment":"Positive control","experimentalConditionsComment":"Positive controls sulfaphenazole, quinidine, and ketoconazole were purchased from Sigma Chemicals (St. Louis, USA). This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.<br /><br />The minus-P450 wells (using luciferin-free water) were negative controls.","resultsComment":"Positive control","internalComment":null,"objectCompoundId":193,"objectMetaboliteCompoundId":194,"precipitantCompoundId":156,"cytochromeB5Id":4,"studyId":129,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":1,"name":"In Vitro Enzyme Inhibition","isInVitro":true,"isTransporter":false,"isEnzyme":true,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000058"},"objectCompound":{"id":193,"name":"6’deoxyluciferin (luciferin h)","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":156,"name":"sulfaphenazole","unii":null,"inChIKey":"QWCJHSGMANYXCW-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":194,"name":"luciferin","unii":null,"inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","publicDescription":null,"internalComment":"AKA d-luciferin","conceptId":null,"enantiomerOfId":null},"enzymes":[{"id":8,"name":"CYP2C9","conceptId":4309227,"experiment_enzyme_xref":{"enzymeId":8,"experimentId":605}}],"transporters":[],"quantifiedMetabolites":[]},{"id":606,"uid":"NPDI-FnVAqw","name":"POS. CONTROL: Inhibition of CYP2D6 by quinidine","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"Not specified.","croIdentifier":null,"comment":"Positive control","experimentalConditionsComment":"Positive controls sulfaphenazole, quinidine, and ketoconazole were purchased from Sigma Chemicals (St. Louis, USA). This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.<br /><br />The minus-P450 wells (using luciferin-free water) were negative controls.","resultsComment":"Positive control","internalComment":null,"objectCompoundId":195,"objectMetaboliteCompoundId":194,"precipitantCompoundId":101,"cytochromeB5Id":4,"studyId":129,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":1,"name":"In Vitro Enzyme Inhibition","isInVitro":true,"isTransporter":false,"isEnzyme":true,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000058"},"objectCompound":{"id":195,"name":"ethylene glycol ester of luciferin 6’methyl ether (luciferin me-ege)","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":101,"name":"quinidine","unii":null,"inChIKey":"LOUPRKONTZGTKE-LHHVKLHASA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":194,"name":"luciferin","unii":null,"inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","publicDescription":null,"internalComment":"AKA d-luciferin","conceptId":null,"enantiomerOfId":null},"enzymes":[{"id":10,"name":"CYP2D6","conceptId":4173631,"experiment_enzyme_xref":{"enzymeId":10,"experimentId":606}}],"transporters":[],"quantifiedMetabolites":[]},{"id":607,"uid":"NPDI-79TG7g","name":"POS. CONTROL: Inhibition of CYP3A4 by ketoconazole","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"Not specified.","croIdentifier":null,"comment":"Positive control","experimentalConditionsComment":"Positive controls sulfaphenazole, quinidine, and ketoconazole were purchased from Sigma Chemicals (St. Louis, USA). This assay was carried out using the P450-Glo™ Screening Systems from Promega, USA.<br /><br />The minus-P450 wells (using luciferin-free water) were negative controls.","resultsComment":"Positive control","internalComment":null,"objectCompoundId":196,"objectMetaboliteCompoundId":194,"precipitantCompoundId":102,"cytochromeB5Id":4,"studyId":129,"experimentTypeId":1,"testSystemId":14,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":1,"name":"In Vitro Enzyme Inhibition","isInVitro":true,"isTransporter":false,"isEnzyme":true,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000058"},"objectCompound":{"id":196,"name":"luciferin 6’benzyl ether (luciferin-be)","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":102,"name":"ketoconazole","unii":null,"inChIKey":"XMAYWYJOQHXEEK-OZXSUGGESA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":194,"name":"luciferin","unii":null,"inChIKey":"IWJYWBVPCGUPLO-KOUNZKNHSA-N","publicDescription":null,"internalComment":"AKA d-luciferin","conceptId":null,"enantiomerOfId":null},"enzymes":[{"id":13,"name":"CYP3A4","conceptId":4306811,"experiment_enzyme_xref":{"enzymeId":13,"experimentId":607}}],"transporters":[],"quantifiedMetabolites":[]}]}]