[{"id":156,"uid":"NPDI-UmIRAQ","name":"Cytochrome P450 inhibition by licorice species Glycyrrhiza inflata and fourteen licorice constituents","napdiIdentifier":null,"overallSummary":"
The potential of licorice dietary supplements to interact with drug metabolism was evaluated by testing extracts of botanically identified licorice species Glycyrrhiza inflata and 14 isolated licorice compounds for inhibition of 9 cytochrome P450 enzymes using a UHPLC-MS/MS cocktail assay. G. inflata strongly inhibited CYP2C enzymes and moderately inhibited CYP1A2, CYP2B6, CYP2D6, and CYP3A4 (midazolam). The licorice compounds isoliquiritigenin, licoricidin, licochalcone A, 18β-glycyrrhetinic acid, and glycycoumarin inhibited one or more members of the CYP2C family of enzymes. Glycycoumarin and licochalcone A inhibited CYP1A2, but only glycycoumarin inhibited CYP2B6. Isoliquiritigenin, glabridin and licoricidin competitively inhibited CYP3A4, while licochalcone A was a mechanism-based inhibitor. The licorice species commonly used in botanical dietary supplements have varying potential for drug-botanical interactions as inhibitors of cytochrome P450 isoforms. Each species of licorice displays a unique profile of constituents with potential for drug interactions.
","pubmedId":28774812,"embaseId":null,"croIdentifier":"UIC","croInformation":"UIC","dateStart":"2017-03-22T00:00:00.000Z","dateEnd":"2017-07-30T00:00:00.000Z","internalComment":null,"status":"published","compoundId":null,"naturalProductUid":"NP-018e008a-0a44-4cee-bb60-dfec34e3285e","naturalProductSampleId":null,"studySourceTypeId":1,"naturalProduct":{"uid":"NP-018e008a-0a44-4cee-bb60-dfec34e3285e","binomial":"Glycyrrhiza inflata","name":"Licorice","itis":null,"srs":"59eda220-bbb5-4dc0-b57a-d010a4222c03","source_id":"","conceptId":null},"compound":null,"studySourceType":{"id":1,"name":"Published report"},"experiments":[{"id":797,"uid":"NPDI-l1_dTA","name":"Chemical characterization of Licorice, Glycyrrhiza inflata","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"% weight compound/weight extract> 100 µg/mL
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":null,"internalComment":null,"objectCompoundId":164,"objectMetaboliteCompoundId":165,"precipitantCompoundId":255,"cytochromeB5Id":null,"studyId":156,"experimentTypeId":1,"testSystemId":6,"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":164,"name":"testosterone","unii":null,"inChIKey":"MUMGGOZAMZWBJJ-DYKIIFRCSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":255,"name":"ethanolic extract of licorice g. inflata","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":165,"name":"6beta-hydroxytestosterone","unii":null,"inChIKey":"XSEGWEUVSZRCBC-ZVBLRVHNSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"enzymes":[{"id":13,"name":"CYP3A4","conceptId":4306811,"experiment_enzyme_xref":{"enzymeId":13,"experimentId":785}}],"transporters":[],"quantifiedMetabolites":[]},{"id":786,"uid":"NPDI-eDM7DQ","name":"Negligible inhibition of CYP2E1 by G. inflata Licorice extract","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"> 100 µg/ml
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":null,"internalComment":null,"objectCompoundId":129,"objectMetaboliteCompoundId":245,"precipitantCompoundId":255,"cytochromeB5Id":null,"studyId":156,"experimentTypeId":1,"testSystemId":6,"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":129,"name":"chloroxazone","unii":null,"inChIKey":"TZFWDZFKRBELIQ-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":255,"name":"ethanolic extract of licorice g. inflata","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":245,"name":"6-hydroxychloroxazone","unii":null,"inChIKey":"AGLXDWOTVQZHIQ-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"enzymes":[{"id":11,"name":"CYP2E1","conceptId":4173608,"experiment_enzyme_xref":{"enzymeId":11,"experimentId":786}}],"transporters":[],"quantifiedMetabolites":[]},{"id":779,"uid":"NPDI-mWgNew","name":"Inhibition of CYP2B6 by G. inflata Licorice extract","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"> 100 µg/mL
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":null,"internalComment":null,"objectCompoundId":6,"objectMetaboliteCompoundId":24,"precipitantCompoundId":255,"cytochromeB5Id":null,"studyId":156,"experimentTypeId":1,"testSystemId":6,"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":6,"name":"bupropion","unii":"01ZG3TPX31","inChIKey":"SNPPWIUOZRMYNY-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":750982,"enantiomerOfId":null},"precipitantCompound":{"id":255,"name":"ethanolic extract of licorice g. inflata","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":24,"name":"hydroxybupropion","unii":null,"inChIKey":"AKOAEVOSDHIVFX-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":4037950,"enantiomerOfId":null},"enzymes":[{"id":6,"name":"CYP2B6","conceptId":4308333,"experiment_enzyme_xref":{"enzymeId":6,"experimentId":779}}],"transporters":[],"quantifiedMetabolites":[]},{"id":777,"uid":"NPDI-x89xLA","name":"Inhibition of CYP1A2 by G. inflata Licorice extract","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"> 100 µg/ml
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":null,"internalComment":null,"objectCompoundId":28,"objectMetaboliteCompoundId":5,"precipitantCompoundId":255,"cytochromeB5Id":null,"studyId":156,"experimentTypeId":1,"testSystemId":6,"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":28,"name":"phenacetin","unii":null,"inChIKey":"CPJSUEIXXCENMM-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":19033710,"enantiomerOfId":null},"precipitantCompound":{"id":255,"name":"ethanolic extract of licorice g. inflata","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":5,"name":"acetaminophen","unii":null,"inChIKey":"RZVAJINKPMORJF-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":1125315,"enantiomerOfId":null},"enzymes":[{"id":4,"name":"CYP1A2","conceptId":4312402,"experiment_enzyme_xref":{"enzymeId":4,"experimentId":777}}],"transporters":[],"quantifiedMetabolites":[]},{"id":781,"uid":"NPDI-Y7VPTg","name":"Inhibition of CYP2C9 by G. inflata Licorice extract","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"> 100 µg/mL
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":null,"internalComment":null,"objectCompoundId":174,"objectMetaboliteCompoundId":175,"precipitantCompoundId":255,"cytochromeB5Id":null,"studyId":156,"experimentTypeId":1,"testSystemId":6,"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":174,"name":"tolbutamide","unii":null,"inChIKey":"JLRGJRBPOGGCBT-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":255,"name":"ethanolic extract of licorice g. inflata","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":175,"name":"hydroxymethyltolbutamide","unii":null,"inChIKey":"SJRHYONYKZIRPM-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"enzymes":[{"id":8,"name":"CYP2C9","conceptId":4309227,"experiment_enzyme_xref":{"enzymeId":8,"experimentId":781}}],"transporters":[],"quantifiedMetabolites":[]},{"id":782,"uid":"NPDI-hR5T0g","name":"Inhibition of CYP2C19 by G. inflata Licorice extract","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"> 100 µg/mL
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":null,"internalComment":null,"objectCompoundId":25,"objectMetaboliteCompoundId":3,"precipitantCompoundId":255,"cytochromeB5Id":null,"studyId":156,"experimentTypeId":1,"testSystemId":6,"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":25,"name":"mephenytoin, (s)-","unii":"D9818430MW","inChIKey":"GMHKMTDVRCWUDX-LBPRGKRZSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":255,"name":"ethanolic extract of licorice g. inflata","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":3,"name":"4-hydroxymephenytoin, (s)-","unii":null,"inChIKey":"OQPLORUDZLXXPD-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"enzymes":[{"id":9,"name":"CYP2C19","conceptId":4311137,"experiment_enzyme_xref":{"enzymeId":9,"experimentId":782}}],"transporters":[],"quantifiedMetabolites":[]},{"id":778,"uid":"NPDI-13n6-Q","name":"Negligible inhibition of CYP2A6 by G. inflata Licorice extract","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"> 100 µg/ml
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":null,"internalComment":null,"objectCompoundId":11,"objectMetaboliteCompoundId":4,"precipitantCompoundId":255,"cytochromeB5Id":null,"studyId":156,"experimentTypeId":1,"testSystemId":6,"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":11,"name":"coumarin","unii":null,"inChIKey":"ZYGHJZDHTFUPRJ-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":19008106,"enantiomerOfId":null},"precipitantCompound":{"id":255,"name":"ethanolic extract of licorice g. inflata","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":4,"name":"7-hydroxycoumarin","unii":null,"inChIKey":"ORHBXUUXSCNDEV-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"enzymes":[{"id":5,"name":"CYP2A6","conceptId":4309826,"experiment_enzyme_xref":{"enzymeId":5,"experimentId":778}}],"transporters":[],"quantifiedMetabolites":[]},{"id":780,"uid":"NPDI-SUW3zQ","name":"Inhibition of CYP2C8 by G. inflata Licorice extract","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"> 100 µg/mL
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":null,"internalComment":null,"objectCompoundId":47,"objectMetaboliteCompoundId":48,"precipitantCompoundId":255,"cytochromeB5Id":null,"studyId":156,"experimentTypeId":1,"testSystemId":6,"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":47,"name":"amodiaquine","unii":null,"inChIKey":"OVCDSSHSILBFBN-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":255,"name":"ethanolic extract of licorice g. inflata","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":48,"name":"n-desethylamodiaquine","unii":null,"inChIKey":"VRXFDHAGFYWGHT-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"enzymes":[{"id":7,"name":"CYP2C8","conceptId":4306333,"experiment_enzyme_xref":{"enzymeId":7,"experimentId":780}}],"transporters":[],"quantifiedMetabolites":[]},{"id":784,"uid":"NPDI-pHgnHQ","name":"Inhibition of CYP3A4 by G. inflata Licorice extract","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"> 100 µg/mL
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":null,"internalComment":null,"objectCompoundId":26,"objectMetaboliteCompoundId":1,"precipitantCompoundId":255,"cytochromeB5Id":null,"studyId":156,"experimentTypeId":1,"testSystemId":6,"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":26,"name":"midazolam","unii":"R60L0SM5BC","inChIKey":"DDLIGBOFAVUZHB-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":708298,"enantiomerOfId":null},"precipitantCompound":{"id":255,"name":"ethanolic extract of licorice g. inflata","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":1,"name":"1'-hydroxymidazolam","unii":null,"inChIKey":"QHSMEGADRFZVNE-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"enzymes":[{"id":13,"name":"CYP3A4","conceptId":4306811,"experiment_enzyme_xref":{"enzymeId":13,"experimentId":784}}],"transporters":[],"quantifiedMetabolites":[]},{"id":783,"uid":"NPDI-1PLoEQ","name":"Inhibition of CYP2D6 by G. inflata Licorice extract","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"> 100 µg/ml
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":null,"internalComment":null,"objectCompoundId":12,"objectMetaboliteCompoundId":13,"precipitantCompoundId":255,"cytochromeB5Id":null,"studyId":156,"experimentTypeId":1,"testSystemId":6,"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":12,"name":"dextromethorphan","unii":"7355X3ROTS","inChIKey":"MKXZASYAUGDDCJ-NJAFHUGGSA-N","publicDescription":null,"internalComment":null,"conceptId":1119510,"enantiomerOfId":null},"precipitantCompound":{"id":255,"name":"ethanolic extract of licorice g. inflata","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":{"id":13,"name":"dextrorphan","unii":null,"inChIKey":"JAQUASYNZVUNQP-PVAVHDDUSA-N","publicDescription":null,"internalComment":null,"conceptId":4349487,"enantiomerOfId":null},"enzymes":[{"id":10,"name":"CYP2D6","conceptId":4173631,"experiment_enzyme_xref":{"enzymeId":10,"experimentId":783}}],"transporters":[],"quantifiedMetabolites":[]}]}]