licoricidin
Inhibition of CYP enzymes by licoricidin 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.

licoricidin

28774812

1 . Inhibition of CYP2C8 by Licoricidin (id=NPDI-Rtoc6Q)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

50 % inhibition

amodiaquine

licoricidin

n-desethylamodiaquine

  • CYP2C8 4306333

Cell fraction Pooled human liver microsomes -7999662

Results

Figure 3

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.2 mg/mL

10 min

NADPH

1 µM

4.25 μg/mL

2 . Inhibition of CYP2B6 by Licoricidin (id=NPDI-fWaGRg)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

50 % inhibition

bupropion 750982

licoricidin

hydroxybupropion 4037950

  • CYP2B6 4308333

Cell fraction Pooled human liver microsomes -7999662

Results

Figure 3

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.2 mg/mL

10 min

NADPH

12 µM

4.25 μg/mL

3 . Inhibition of CYP2C19 by Licoricidin (id=NPDI-gQk-ng)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

50 % inhibition

mephenytoin, (s)-

licoricidin

4-hydroxymephenytoin, (s)-

  • CYP2C19 4311137

Cell fraction Pooled human liver microsomes -7999662

Results

Figure 3

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.2 mg/mL

10 min

NADPH

50 µM

4.25 μg/mL

4 . Inhibition of CYP3A4 by Licoricidin (id=NPDI-DDS1fQ)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

50 % inhibition

testosterone

licoricidin

6beta-hydroxytestosterone

  • CYP3A4 4306811

Cell fraction Pooled human liver microsomes -7999662

Results

Figure 3

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.2 mg/mL

10 min

NADPH

50 µM

4.25 μg/mL

5 . Inhibition of CYP2C9 by Licoricidin (id=NPDI-fbIOUw)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used —

50 % inhibition

tolbutamide

licoricidin

hydroxymethyltolbutamide

  • CYP2C9 4309227

Cell fraction Pooled human liver microsomes -7999662

Results

Figure 3

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.2 mg/mL

10 min

NADPH

100 µM

4.25 μg/mL