Goldenseal (Hydrastis canadensis)
An in vitro Evaluation of Cytochrome P450 Inhibition and P-Glycoprotein Interaction with Goldenseal, Ginkgo biloba, Grape Seed, Milk Thistle, and Ginseng Extracts and Their Constituents
CSV
JSON
Drug-herb interactions can result from the modulation of the activities of cytochrome P450 (P450) and/or drug transporters. The effect of extracts and individual constituents of goldenseal, Ginkgo biloba (and its hydrolyzate), grape seed, milk thistle, and ginseng on the activities of cytochrome P450 enzymes CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 in human liver microsomes were determined using enzyme-selective probe substrates, and their effect on human P-glycoprotein (Pgp) was determined using a baculovirus expression system by measuring the verapamil-stimulated, vanadate-sensitive ATPase activity. Extracts were analyzed by HPLC to standardize their concentration(s) of constituents associated with the pharmacological activity, and to allow comparison of their effects on P450 and Pgp with literature values. Many of the extracts/constituents exerted > or = 50 % inhibition of P450 activity. These include those from goldenseal (normalized to alkaloid content) inhibiting CYP2C8, CYP2D6, and CYP3A4 at 20 microM, ginkgo inhibiting CYP2C8 at 10 microM, grape seed inhibiting CYP2C9 and CYP3A4 at 10 microM, milk thistle inhibiting CYP2C8 at 10 microM, and ginsenosides F1 and Rh1 (but not ginseng extract) inhibiting CYP3A4 at 10 microM. Goldenseal extracts/constituents (20 microM, particularly hydrastine) and ginsenoside Rh1 stimulated ATPase at about half of the activity of the model substrate, verapamil (20 microM). The data suggest that the clearance of a variety of drugs may be diminished by concomitant use of these herbs via inhibition of P450 enzymes, but less so by Pgp-mediated effects.
1 . 1A2 Inhibition by Hydrastine (id=NPDI-59mQTg)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP1A2 4312402
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
2 . 2D6 Inhibition by Aq GS Extract (id=NPDI-IdieOw)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP2D6 4173631
Cell fraction Pooled human liver microsomes -7999662
Results
Estimate Fig 1 at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
3 . 2D6 Inhibition by Berberine (id=NPDI-cRrAsg)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP2D6 4173631
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
4 . 2D6 Inhibition by Ethanolic GS Extract (id=NPDI-PqZKVg)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP2D6 4173631
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 Estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
5 . 2C19 Inhibition by Aq GS Extract (id=NPDI-0_ey6g)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP2C19 4311137
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 Estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
6 . 2C19 Inhibition by Ethanolic GS Extract (id=NPDI-3QKJaw)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP2C19 4311137
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
7 . 2C19 Inhibition by Hydrastine (id=NPDI-6cuc3g)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP2C19 4311137
Cell fraction Pooled human liver microsomes -7999662
Results
Estimate from Fig 1 at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
8 . 3A4 Inhibition by Aq GS Extract (MDZ) (id=NPDI-Z0x9xQ)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP3A4 4306811
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 Estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
9 . 3A4 Inhibition by Ethanolic GS Extract (MDZ) (id=NPDI-cnkDpg)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP3A4 4306811
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 Estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
10 . 3A4 Inhibition by Hydrastine (MDZ) (id=NPDI-_UID1w)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP3A4 4306811
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 Estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
11 . 2E1 Inhibition by Berberine (id=NPDI-ij84RA)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP2E1 4173608
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
12 . 2C8 Inhibition by Ethanolic GS Extract (id=NPDI-cesmqQ)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP2C8 4306333
Cell fraction Pooled human liver microsomes -7999662
Results
Estimate Fig 1 at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
13 . 2C8 Inhibition by Hydrastine (id=NPDI-VqNO0Q)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP2C8 4306333
Cell fraction Pooled human liver microsomes -7999662
Results
Estimate of inhibition Fig 1 at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
14 . 3A4 Inhibition by Aq GS Extract (Testosterone) (id=NPDI-cYwbww)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP3A4 4306811
Cell fraction Pooled human liver microsomes -7999662
Results
Estimate Fig 1 at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
15 . 3A4 Inhibition by Berberine (Testosterone) (id=NPDI-1ijwVg)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP3A4 4306811
Cell fraction Pooled human liver microsomes -7999662
Results
Estimate from Fig 1 at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
16 . 3A4 Inhibition by Ethanolic GS Extract (Testosterone) (id=NPDI-ibIkjQ)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP3A4 4306811
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 Estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
17 . 3A4 Inhibition by Hydrastine (Testosterone) (id=NPDI-5wiIYg)
In Vitro Enzyme Inhibition Experiment
Inhibition was detected. Cutoff used — not specified
- CYP3A4 4306811
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 Estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
18 . 1A2 Inhibition by Ethanolic GS Extract (id=NPDI-oVpWlA)
In Vitro Enzyme Inhibition Experiment
Negligible Inhibition was detected. Cutoff used — not specified
- CYP1A2 4312402
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 Estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
19 . 2D6 Inhibition by Hydrastine (id=NPDI-6gn9Dg)
In Vitro Enzyme Inhibition Experiment
Negligible Inhibition was detected. Cutoff used — not specified
- CYP2D6 4173631
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
20 . 2C19 Inhibition by Berberine (id=NPDI-c2kfPA)
In Vitro Enzyme Inhibition Experiment
Negligible Inhibition was detected. Cutoff used — not specified
- CYP2C19 4311137
Cell fraction Pooled human liver microsomes -7999662
Results
estimate from Fig 1 at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
21 . 2E1 Inhibition by Hydrastine (id=NPDI-NNibEQ)
In Vitro Enzyme Inhibition Experiment
Negligible Inhibition was detected. Cutoff used — not specified
- CYP2E1 4173608
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 Estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
22 . 2C8 Inhibition by Aq GS Extract (id=NPDI-37V97Q)
In Vitro Enzyme Inhibition Experiment
Negligible Inhibition was detected. Cutoff used — not specified
- CYP2C8 4306333
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 Estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
23 . 2C8 Inhibition by Berberine (id=NPDI-2kECKw)
In Vitro Enzyme Inhibition Experiment
Negligible Inhibition was detected. Cutoff used — not specified
- CYP2C8 4306333
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
24 . 2C9 Inhibition by Ethanolic GS Extract (id=NPDI-uBMfpQ)
In Vitro Enzyme Inhibition Experiment
Negligible Inhibition was detected. Cutoff used — not specified
- CYP2C9 4309227
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 Estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM
25 . 2C9 Inhibition by Hydrastine (id=NPDI-dgm1Ww)
In Vitro Enzyme Inhibition Experiment
Negligible Inhibition was detected. Cutoff used — not specified
- CYP2C9 4309227
Cell fraction Pooled human liver microsomes -7999662
Results
Fig 1 estimate at 20 μM
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
In-house preparation
HHM-247 and HHM-258
15 min
NADPH
10 min
No NADPH with precipitant
1 or 20 μM