licochalcone a
Inhibition of CYP enzymes by licochalcone a CSV JSON

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.

licochalcone a

28774812


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

amodiaquine

licochalcone a

n-desethylamodiaquine

  • 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

bupropion 750982

licochalcone a

hydroxybupropion 4037950

  • 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

dextromethorphan 1119510

licochalcone a

dextrorphan 4349487

  • 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

mephenytoin, (s)-

licochalcone a

4-hydroxymephenytoin, (s)-

  • 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

midazolam 708298

licochalcone a

1'-hydroxymidazolam

  • 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

phenacetin 19033710

licochalcone a

acetaminophen 1125315

  • 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

testosterone

licochalcone a

6beta-hydroxytestosterone

  • 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

tolbutamide

licochalcone a

hydroxymethyltolbutamide

  • 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

chloroxazone

licochalcone a

6-hydroxychloroxazone

  • 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

coumarin 19008106

licochalcone a

7-hydroxycoumarin

  • 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