Goldenseal (Hydrastis canadensis)
R21 Goldenseal Project
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Inhibition of PMAT, THTR2, and OCT3 transporters were tested using both goldenseal extract and berberine. Two pharmacokinetic studies measured the Cmax, AUC, AUCR, half-life, and Tmax of metformin alone and in combination with other test articles (goldenseal extract, berberine, (-)-β-hydrastine, and imatinib).
1 . Inhibition of OCT3 by Berberine (id=NPDI-ofSGNw)
In Vitro Transporter Inhibition Experiment
Inhibition was detected. Cutoff used —
Inhibition
- OCT3 (SLC22A3)
Transfected / siRNA knock-out / injected cells HEK293 transfected cells
Berberine is a constituent of Goldenseal.
Results
Goldenseal extract, normalized to berberine content, was the strongest inhibitor of OCT3, PMAT, and THTR2 transporter activity.
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
DMSO was used as vehicle.
1×10^5 cells/well
50 µL of precipitant per well, ~ 1 mg per well of protein content (not used in calculations)
96 well
16-24h
p18
N/A
N/A
3 minutes
37°C
7.4
0.02 µM
0, 0.27, 0.82, 2.47, 7.41, 22.22, 66.67, 200 µM
2 . Inhibition of PMAT by Berberine (id=NPDI-eiNjiQ)
In Vitro Transporter Inhibition Experiment
Inhibition was detected. Cutoff used —
Inhibition
- ENT4 (SLC29A4)
Transfected / siRNA knock-out / injected cells HEK293 transfected cells
Berberine is a constituent of Goldenseal.
Results
Goldenseal extract, normalized to berberine content, was the strongest inhibitor of OCT3, PMAT, and THTR2 transporter activity.
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
DMSO was used as vehicle.
1×10^5 cells/well
50 µL of precipitant per well, ~ 1 mg per well of protein content (not used in calculations)
96 well
16-24h
P17
N/A
N/A
2 minutes
37°C
6.6
10 µM
0, 0.27, 0.82, 2.47, 7.41, 22.22, 66.67, 200 µM
3 . Inhibition of OCT3 by Goldenseal (id=NPDI-WdP3OQ)
In Vitro Transporter Inhibition Experiment
Inhibition was detected. Cutoff used —
Inhibition
- OCT3 (SLC22A3)
Transfected / siRNA knock-out / injected cells HEK293 transfected cells
Goldenseal was normalized to berberine content.
Results
Goldenseal extract, normalized to berberine content, was the strongest inhibitor of OCT3, PMAT, and THTR2 transporter activity.
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
DMSO was used as vehicle.
1×10^5 cells/well
50 µL of precipitant per well, ~ 1 mg per well of protein content (not used in calculations)
96 well
16-24h
p18
N/A
N/A
3 minutes
37°C
7.4
0.02 µM
0, 0.02, 0.07, 0.22, 0.65, 1.94, 5.83, 17.5 µM
Dr. Nicholas Oberlies (UNCG)
4 . Inhibition of PMAT by Goldenseal (id=NPDI-_tymTQ)
In Vitro Transporter Inhibition Experiment
Inhibition was detected. Cutoff used —
Inhibition
- ENT4 (SLC29A4)
Transfected / siRNA knock-out / injected cells HEK293 transfected cells
Goldenseal was normalized to berberine content.
Results
Goldenseal extract, normalized to berberine content, was the strongest inhibitor of OCT3, PMAT, and THTR2 transporter activity.
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
DMSO was used as vehicle.
1×10^5 cells/well
50 µL of precipitant per well, ~ 1 mg per well of protein content (not used in calculations)
96 well
16-24h
p17
N/A
N/A
2 minutes
37°C
6.6
10 µM
0, 0.02, 0.07, 0.22, 0.65, 1.94, 5.83, 17.5 µM
Dr. Nicholas Oberlies (UNCG)
5 . Inhibition of THTR2 by Berberine (id=NPDI-NyZpzA)
In Vitro Transporter Inhibition Experiment
Inhibition was detected. Cutoff used —
Inhibition
- THTR2 (SLC19A3)
Transfected / siRNA knock-out / injected cells HEK293 transfected cells
Berberine is a constituent of Goldenseal.
Results
Goldenseal extract, normalized to berberine content, was the strongest inhibitor of OCT3, PMAT, and THTR2 transporter activity.
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
DMSO was used as vehicle.
1×10^5 cells/well
50 µL of precipitant per well, ~ 1 mg per well of protein content (not used in calculations)
96 well
16-24h
p19
N/A
N/A
3 minutes
37°C
7.4
0.03 µM
0, 0.27, 0.82, 2.47, 7.41, 22.22, 66.67, 200 µM
6 . Inhibition of THTR2 by Goldenseal (id=NPDI-g3SJcw)
In Vitro Transporter Inhibition Experiment
Inhibition was detected. Cutoff used —
Inhibition
- THTR2 (SLC19A3)
Transfected / siRNA knock-out / injected cells HEK293 transfected cells
Goldenseal was normalized to berberine content.
Results
Goldenseal extract, normalized to berberine content, was the strongest inhibitor of OCT3, PMAT, and THTR2 transporter activity.
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
DMSO was used as vehicle.
1×10^5 cells/well
50 µL of precipitant per well, ~ 1 mg per well of protein content (not used in calculations)
96 well
16-24h
p19
N/A
N/A
3 minutes
37°C
7.4
0.03 µM
0, 0.02, 0.07, 0.22, 0.65, 1.94, 5.83, 17.5 µM
Dr. Nicholas Oberlies (UNCG)
1 . Oral Metformin/Oral Inhibitor Mouse Study - (-)-β-hydrastine (id=NPDI-yehRxQ)
In Vivo Interaction Study
No Effect (based on bioequivalence limits) was detected.
metformin 1503297
Results
Control:
-AUC0-4h: 4.7 (24)
-AUCR (ratio of AUC0-4h in presence of test article to vehicle; values represented as geometric means with 90% CI): N/A
-AUCR (ratio of AUC0-12h in presence of test article to vehicle; values represented as geometric means with 90% CI): N/A
Test:
-AUC0-4h: 4.4 (21)
-AUCR (ratio of AUC0-4h in presence of test article to vehicle; values represented as geometric means with 90% CI): 0.93 (0.82-1.07)
-AUCR (ratio of AUC0-12h in presence of test article to vehicle; values represented as geometric means with 90% CI): 0.95 (0.82-1.11)
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
Blood was used for LC-MS analysis.
Single dosing
Males
FVB
8 per test group
The form has been tweaked for the mice study.
Study population: mice
Study population phenotype: Jackson laboratory (Bar Harbor, Maine)
0.25, 0.5, 1, 2, 4, 8, and 12 h
None
Drug or Natural Product Administration
Oral
Liquid
Metformin (10 mg/kg)
Single dose administered by oral gavage at 10 ml/kg for both goldenseal and other test articles.
Once
Oral
N/A
(–)-β-Hydrastine (46 mg/kg)
Single dose administered by oral gavage at 10 ml/kg for both goldenseal and other test articles.
Once
Goldenseal
Yes - sent to Clarke lab by Dr. Oberlies at UNCG
N/A
Pharmacodynamics (PD) & Adverse Events
N/A
N/A
N/A
2 . Intravenous Metformin/Oral Inhibitor Mouse Study - Goldenseal Extract (id=NPDI-n4yXtA)
In Vivo Interaction Study
No Effect (based on bioequivalence limits) was detected.
metformin 1503297
Results
Control:
-AUCR (ratio of AUC0-12h in presence of test article to vehicle; values represented as geometric means with 90% CI): N/A
Test:
-AUCR (ratio of AUC0-12h in presence of test article to vehicle; values represented as geometric means with 90% CI): 1.27 (1.10-1.48)
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
Blood was used for LC-MS analysis.
Single dosing
Males
FVB
7 per test group
The form has been tweaked for the mice study.
Study population: mice
Study population phenotype: Jackson laboratory (Bar Harbor, Maine)
0.083, 0.25, 0.5, 1, 2, 4, 8, and 12 h
None
Drug or Natural Product Administration
Intravenous
Liquid
Metformin (10 mg/kg)
Single dose of goldenseal and imatinib administered by oral gavage at 10 ml/kg for both goldenseal and metformin. Metformin was administered by retroorbital injection.
Once
Oral
N/A
Goldenseal (500 mg/kg)
Single dose of goldenseal and imatinib administered by oral gavage at 10 ml/kg for both goldenseal and metformin. Metformin was administered by retroorbital injection.
Once
Goldenseal
Yes - sent to Clarke lab by Dr. Oberlies at UNCG
N/A
Pharmacodynamics (PD) & Adverse Events
N/A
N/A
N/A
3 . Oral Metformin/Oral Inhibitor Mouse Study - Berberine (id=NPDI-KWj0Jg)
In Vivo Interaction Study
No Effect (based on bioequivalence limits) was detected.
Results
Control:
-AUC0-4h: 4.7 (24)
-AUCR (ratio of AUC0-4h in presence of test article to vehicle; values represented as geometric means with 90% CI): N/A
-AUCR (ratio of AUC0-12h in presence of test article to vehicle; values represented as geometric means with 90% CI): N/A
Test:
-AUC0-4h: 4.1 (26)
-AUCR (ratio of AUC0-4h in presence of test article to vehicle; values represented as geometric means with 90% CI): 0.87 (0.67-1.15)
-AUCR (ratio of AUC0-12h in presence of test article to vehicle; values represented as geometric means with 90% CI): 0.92 (0.71-1.19)
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
Blood was used for LC-MS analysis.
Single dosing
Males
FVB
8 per test group
The form has been tweaked for the mice study.
Study population: mice
Study population phenotype: Jackson laboratory (Bar Harbor, Maine)
0.25, 0.5, 1, 2, 4, 8, and 12 h
None
Drug or Natural Product Administration
Oral
Liquid
Metformin (10 mg/kg)
Single dose administered by oral gavage at 10 ml/kg for both goldenseal and other test articles.
Once
Oral
N/A
Berberine (71 mg/kg)
Single dose administered by oral gavage at 10 ml/kg for both goldenseal and other test articles.
Once
Goldenseal
Yes - sent to Clarke lab by Dr. Oberlies at UNCG
N/A
Pharmacodynamics (PD) & Adverse Events
N/A
N/A
N/A
4 . Intravenous Metformin/Oral Inhibitor Mouse Study - Imatinib (id=NPDI-YlzfNg)
In Vivo Interaction Study
No Effect (based on bioequivalence limits) was detected.
Results
Control:
-AUCR (ratio of AUC0-12h in presence of test article to vehicle; values represented as geometric means with 90% CI): N/A
Test:
-AUCR (ratio of AUC0-12h in presence of test article to vehicle; values represented as geometric means with 90% CI): 1.20 (0.97-1.50)
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
Blood was used for LC-MS analysis.
Single dosing
Males
FVB
7 per test group
The form has been tweaked for the mice study.
Study population: mice
Study population phenotype: Jackson laboratory (Bar Harbor, Maine)
0.083, 0.25, 0.5, 1, 2, 4, 8, and 12 h
None
Drug or Natural Product Administration
Intravenous
Liquid
Metformin (10 mg/kg)
Single dose of goldenseal and imatinib administered by oral gavage at 10 ml/kg for both goldenseal and metformin. Metformin was administered by retroorbital injection.
Once
Oral
N/A
Imatinib (100 mg/kg)
Single dose of goldenseal and imatinib administered by oral gavage at 10 ml/kg for both goldenseal and metformin. Metformin was administered by retroorbital injection.
Once
Goldenseal
Yes - sent to Clarke lab by Dr. Oberlies at UNCG
N/A
Pharmacodynamics (PD) & Adverse Events
N/A
N/A
N/A
5 . Oral Metformin/Oral Inhibitor Mouse Study - Goldenseal Extract (id=NPDI-dS7vAQ)
Results
Control:
-AUC0-4h: 4.7 (24)
-AUCR (ratio of AUC0-4h in presence of test article to vehicle; values represented as geometric means with 90% CI): N/A
-AUCR (ratio of AUC0-12h in presence of test article to vehicle; values represented as geometric means with 90% CI): N/A
Test:
-AUC0-4h: 3.3 (17); p-value < 0.05 compared to vehicle by 1-way ANOVA with Dunnett’s post-test
-AUCR (ratio of AUC0-4h in presence of test article to vehicle; values represented as geometric means with 90% CI): 0.69 (0.59-0.83)
-AUCR (ratio of AUC0-12h in presence of test article to vehicle; values represented as geometric means with 90% CI): 0.83 (0.74-0.95)
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
Blood was used for LC-MS analysis.
Single dosing
Males
FVB
8 per test group
The form has been tweaked for the mice study.
Study population: mice
Study population phenotype: Jackson laboratory (Bar Harbor, Maine)
0.25, 0.5, 1, 2, 4, 8, and 12 h
None
Drug or Natural Product Administration
Oral
Liquid
Metformin (10 mg/kg)
Single dose administered by oral gavage at 10 ml/kg for both goldenseal and other test articles.
Once
Oral
N/A
Goldenseal (500 mg/kg)
Single dose administered by oral gavage at 10 ml/kg for both goldenseal and other test articles.
Once
Goldenseal
Yes - sent to Clarke lab by Dr. Oberlies at UNCG
N/A
Pharmacodynamics (PD) & Adverse Events
N/A
N/A
N/A
6 . Oral Metformin/Oral Inhibitor Mouse Study - Imatinib (id=NPDI-yewsDg)
Results
Control:
-AUC0-4h: 4.7 (24)
-AUCR (ratio of AUC0-4h in presence of test article to vehicle; values represented as geometric means with 90% CI): N/A
-AUCR (ratio of AUC0-12h in presence of test article to vehicle; values represented as geometric means with 90% CI): N/A
Test:
-AUC0-4h: 3.7 (12)
-AUCR (ratio of AUC0-4h in presence of test article to vehicle; values represented as geometric means with 90% CI): 0.79 (0.65-0.96)
-AUCR (ratio of AUC0-12h in presence of test article to vehicle; values represented as geometric means with 90% CI): 0.89 (0.74-1.07)
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
Blood was used for LC-MS analysis.
Single dosing
Males
FVB
8 per test group
The form has been tweaked for the mice study.
Study population: mice
Study population phenotype: Jackson laboratory (Bar Harbor, Maine)
0.25, 0.5, 1, 2, 4, 8, and 12 h
None
Drug or Natural Product Administration
Oral
Liquid
Metformin (10 mg/kg)
Single dose administered by oral gavage at 10 ml/kg for both goldenseal and other test articles.
Once
Oral
N/A
Imatinib (100 mg/kg)
Single dose administered by oral gavage at 10 ml/kg for both goldenseal and other test articles.
Once
Goldenseal
Yes - sent to Clarke lab by Dr. Oberlies at UNCG
N/A
Pharmacodynamics (PD) & Adverse Events
N/A
N/A
N/A