Goldenseal (Hydrastis canadensis)
R21 Goldenseal Project CSV JSON

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).

Goldenseal (Hydrastis canadensis)

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

(-)-beta-hydrastine

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

Population

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)

Pharmacokinetic (PK) Sampling Information

0.25, 0.5, 1, 2, 4, 8, and 12 h

None

Drug or Natural Product Administration
Object Administration — metformin

Oral

Liquid

Metformin (10 mg/kg)

Single dose administered by oral gavage at 10 ml/kg for both goldenseal and other test articles.

Once

Precipitant Administration — (-)-beta-hydrastine

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

Natural Product Characteristics

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

aqueous goldenseal extract

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

Population

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)

Pharmacokinetic (PK) Sampling Information

0.083, 0.25, 0.5, 1, 2, 4, 8, and 12 h

None

Drug or Natural Product Administration
Object Administration — metformin

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

Precipitant Administration — aqueous goldenseal extract

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

Natural Product Characteristics

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.

metformin 1503297

berberine 19012197

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

Population

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)

Pharmacokinetic (PK) Sampling Information

0.25, 0.5, 1, 2, 4, 8, and 12 h

None

Drug or Natural Product Administration
Object Administration — metformin

Oral

Liquid

Metformin (10 mg/kg)

Single dose administered by oral gavage at 10 ml/kg for both goldenseal and other test articles.

Once

Precipitant Administration — berberine

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

Natural Product Characteristics

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.

metformin 1503297

imatinib

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

Population

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)

Pharmacokinetic (PK) Sampling Information

0.083, 0.25, 0.5, 1, 2, 4, 8, and 12 h

None

Drug or Natural Product Administration
Object Administration — metformin

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

Precipitant Administration — imatinib

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

Natural Product Characteristics

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)

In Vivo Interaction Study

Decreased systemic exposure was detected.

metformin 1503297

aqueous goldenseal extract

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

Population

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)

Pharmacokinetic (PK) Sampling Information

0.25, 0.5, 1, 2, 4, 8, and 12 h

None

Drug or Natural Product Administration
Object Administration — metformin

Oral

Liquid

Metformin (10 mg/kg)

Single dose administered by oral gavage at 10 ml/kg for both goldenseal and other test articles.

Once

Precipitant Administration — aqueous goldenseal extract

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

Natural Product Characteristics

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)

In Vivo Interaction Study

Decreased systemic exposure was detected.

metformin 1503297

imatinib

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

Population

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)

Pharmacokinetic (PK) Sampling Information

0.25, 0.5, 1, 2, 4, 8, and 12 h

None

Drug or Natural Product Administration
Object Administration — metformin

Oral

Liquid

Metformin (10 mg/kg)

Single dose administered by oral gavage at 10 ml/kg for both goldenseal and other test articles.

Once

Precipitant Administration — imatinib

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

Natural Product Characteristics

Goldenseal

Yes - sent to Clarke lab by Dr. Oberlies at UNCG

N/A

Pharmacodynamics (PD) & Adverse Events

N/A

N/A

N/A

1 . Inhibition of OCT3 by Berberine (id=NPDI-ofSGNw)

In Vitro Transporter Inhibition Experiment

Inhibition was detected.  Cutoff used —

Inhibition

mpp+

berberine 19012197

  • 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.

Cell Culture Conditions

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

Viability and Function

N/A

N/A

Assay Conditions

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

mpp+

berberine 19012197

  • 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.

Cell Culture Conditions

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

Viability and Function

N/A

N/A

Assay Conditions

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 PMAT by Goldenseal (id=NPDI-_tymTQ)

In Vitro Transporter Inhibition Experiment

Inhibition was detected.  Cutoff used —

Inhibition

mpp+

goldenseal root extract

  • 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.

Cell Culture Conditions

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

Viability and Function

N/A

N/A

Assay Conditions

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)

4 . Inhibition of OCT3 by Goldenseal (id=NPDI-WdP3OQ)

In Vitro Transporter Inhibition Experiment

Inhibition was detected.  Cutoff used —

Inhibition

mpp+

goldenseal root extract

  • 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.

Cell Culture Conditions

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

Viability and Function

N/A

N/A

Assay Conditions

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)

5 . Inhibition of THTR2 by Berberine (id=NPDI-NyZpzA)

In Vitro Transporter Inhibition Experiment

Inhibition was detected.  Cutoff used —

Inhibition

thiamine

berberine 19012197

  • 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.

Cell Culture Conditions

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

Viability and Function

N/A

N/A

Assay Conditions

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

thiamine

goldenseal root extract

  • 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.

Cell Culture Conditions

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

Viability and Function

N/A

N/A

Assay Conditions

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)