Licorice (Glycyrrhiza inflata)
Cytochrome P450 inhibition by licorice species Glycyrrhiza inflata and fourteen licorice constituents
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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.
1 . Inhibition of CYP2C8 by G. inflata Licorice extract (id=NPDI-SUW3zQ)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
> 100 µg/mL
- CYP2C8 4306333
Cell fraction Pooled human liver microsomes -7999662
Results
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
0.2 mg/mL
10 min
NADPH
1 µM
11 concentrations from 0.005–250 μg/mL
2 . Inhibition of CYP2B6 by G. inflata Licorice extract (id=NPDI-mWgNew)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
> 100 µg/mL
- CYP2B6 4308333
Cell fraction Pooled human liver microsomes -7999662
Results
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
0.2 mg/mL
10 min
NADPH
12 µM
11 concentrations from 0.005–250 μg/mL
3 . Inhibition of CYP2D6 by G. inflata Licorice extract (id=NPDI-1PLoEQ)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
> 100 µg/ml
- CYP2D6 4173631
Cell fraction Pooled human liver microsomes -7999662
Results
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
0.2 mg/mL
10 min
NADPH
2.5 µM
11 concentrations from 0.005–250 μg/mL
4 . Inhibition of CYP2C19 by G. inflata Licorice extract (id=NPDI-hR5T0g)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
> 100 µg/mL
- CYP2C19 4311137
Cell fraction Pooled human liver microsomes -7999662
Results
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
0.2 mg/mL
10 min
NADPH
50 µM
11 concentrations from 0.005–250 μg/mL
5 . Inhibition of CYP3A4 by G. inflata Licorice extract (id=NPDI-pHgnHQ)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
> 100 µg/mL
- CYP3A4 4306811
Cell fraction Pooled human liver microsomes -7999662
Results
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
0.2 mg/mL
10 min
NADPH
2.5 µM
11 concentrations from 0.005–250 μg/mL
6 . Inhibition of CYP1A2 by G. inflata Licorice extract (id=NPDI-x89xLA)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
> 100 µg/ml
- CYP1A2 4312402
Cell fraction Pooled human liver microsomes -7999662
Results
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
0.2 mg/mL
10 min
NADPH
100 µM
11 concentrations from 0.005–250 μg/mL
7 . Inhibition of CYP3A4 by G. inflata Licorice extract (id=NPDI-beIHRg)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
> 100 µg/mL
- CYP3A4 4306811
Cell fraction Pooled human liver microsomes -7999662
Results
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
0.2 mg/mL
10 min
NADPH
50 µM
11 concentrations from 0.005–250 μg/mL
8 . Inhibition of CYP2C9 by G. inflata Licorice extract (id=NPDI-Y7VPTg)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
> 100 µg/mL
- CYP2C9 4309227
Cell fraction Pooled human liver microsomes -7999662
Results
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
0.2 mg/mL
10 min
NADPH
100 µM
11 concentrations from 0.005–250 μg/mL
9 . Negligible inhibition of CYP2E1 by G. inflata Licorice extract (id=NPDI-eDM7DQ)
In Vitro Enzyme Inhibition Experiment
Negligible Inhibition was detected. Cutoff used —
> 100 µg/ml
- CYP2E1 4173608
Cell fraction Pooled human liver microsomes -7999662
Results
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
0.2 mg/mL
10 min
NADPH
15 µM
11 concentrations from 0.005–250 μg/mL
10 . Negligible inhibition of CYP2A6 by G. inflata Licorice extract (id=NPDI-13n6-Q)
In Vitro Enzyme Inhibition Experiment
Negligible Inhibition was detected. Cutoff used —
> 100 µg/ml
- CYP2A6 4309826
Cell fraction Pooled human liver microsomes -7999662
Results
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
0.2 mg/mL
10 min
NADPH
1.5 µM
11 concentrations from 0.005–250 μg/mL
1 . Chemical characterization of Licorice, Glycyrrhiza inflata (id=NPDI-l1_dTA)
Characterization of Material Study
Results
% weight compound/weight extract
glabridin, licoricidin had quantities of 0 and were excluded from the results
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
ethanol, isopropanol, water (90:5:5, v/v/v)
species checked with DNA barcoding, and comparison with voucher specimens at the Field Museum of Natural History, Chicago.
UHPLC-MS/MS