licochalcone a
Inhibition of CYP enzymes by licochalcone a
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The potential of licorice dietary supplements to interact with drug metabolism was evaluated by testing extracts of three botanically identified licorice species (Glycyrrhiza glabra L., Glycyrrhiza uralensis Fish. ex DC. and Glycyrrhiza inflata Batalin) and 14 isolated licorice compounds for inhibition of 9 cytochrome P450 enzymes using a UHPLC-MS/MS cocktail assay. G. glabra showed moderate inhibitory effects against CYP2B6, CYP2C8, CYP2C9, and CYP2C19, and weak inhibition against CYP3A4 (testosterone). In contrast, G. uralensis strongly inhibited CYP2B6 and moderately inhibited CYP2C8, CYP2C9 and CYP2C19, and 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 (specific to G. inflata roots) was a mechanism-based inhibitor. The three 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.
Compilation of raw NMR data (FID) with structural description (pms file) and annotation (PDF):
https://dataverse.harvard.edu/dataset.xhtml?persistentId=doi:10.7910/DVN/DFAVTE
1 . Inhibition of CYP2C8 by Licochalcone A (id=NPDI-DJNbNQ)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
50 % inhibition
- CYP2C8 4306333
Cell fraction Pooled human liver microsomes -7999662
Results
Results come from both Table 1 and Figure 3
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
0.2 mg/mL
10 min
NADPH
1 µM
3.38 μg/mL
2 . Inhibition of CYP2B6 by Licochalcone A (id=NPDI-uh21Qg)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
> 25 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 Licochalcone A (id=NPDI-mJF8xw)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
> 25 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 Licochalcone A (id=NPDI-HNpTng)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
50 % inhibition
- CYP2C19 4311137
Cell fraction Pooled human liver microsomes -7999662
Results
Results come from both Table 1 and Figure 3
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
0.2 mg/mL
10 min
NADPH
50 µM
3.38 μg/mL
5 . Inhibition of CYP3A4 by Licochalcone A (id=NPDI-CAfs7A)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
> 25 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 CYP2A1 by Licochalcone A (id=NPDI-Rx5N8Q)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
> 25 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 Licochalcone A (id=NPDI-NUpDbg)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
50 % inhibition
- CYP3A4 4306811
Cell fraction Pooled human liver microsomes -7999662
Results
Results come from both Table 1 and Figure 3
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
0.2 mg/mL
10 min
NADPH
50 µM
3.38 μg/mL
8 . Inhibition of CYP2C9 by Licochalcone A (id=NPDI-AVsEiw)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used —
50 % inhibition
- CYP2C9 4309227
Cell fraction Pooled human liver microsomes -7999662
Results
Results come from both Table 1 and Figure 3
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
0.2 mg/mL
10 min
NADPH
100 µM
3.38 μg/mL
9 . Negligible inhibition of CYP2E1 by Licochalcone A (id=NPDI-4WGfNA)
In Vitro Enzyme Inhibition Experiment
Negligible Inhibition was detected. Cutoff used —
> 25 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 Licochalcone A (id=NPDI-eb9bKA)
In Vitro Enzyme Inhibition Experiment
Negligible Inhibition was detected. Cutoff used —
> 25 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