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
Abstract
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.
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Berberine inhibits CYP3A4.
“inhibition, and transcriptional induction, of CYP3A4”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [36]
Berberine is far from inert.
“yet berberine is far from inert”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [36]
In vitro, berberine inhibits CYP2D6 with IC50 values on the order of 7-45 μM and CYP3A4/CYP2C9 with lower potency.
“In vitro, berberine inhibits CYP2D6 with greater potency (reported IC50 values on the order of 7–45 µM) and CYP3A4/CYP2C9 with lower potency [36,68,69].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [36]
Local inhibition of CYP3A4 and P-glycoprotein in the intestinal wall can markedly increase the absorbed fraction of the victim drug, independently of berberine's modest plasma concentrations.
“Local inhibition of CYP3A4 and P-glycoprotein in the intestinal wall can markedly increase the absorbed fraction of the victim drug, independently of berberine’s modest plasma concentrations [36,58].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [36]
Berberine inhibits major cytochrome P450 enzymes and modulates membrane transporters essential to drug disposition.
“Berberine inhibits major cytochrome P450 enzymes and modulates membrane transporters essential to drug disposition [35,36,37]”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [36]
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- Authors
- Etheridge, A., Black, S., Patel, P., So, J., & Mathews, J.
- Affiliations
- RTI International (US)
- Venue
- Planta Medica
- Publisher
- Georg Thieme Verlag KG
- Published
- 2007-07
- Volume
- 73
- Issue
- 8
- Pages
- 731-741
- ISSN
- 0032-0943 (ISSN-L)
- 1439-0221
- OpenAlex
- W1977526476
- Cited by
- 102
- References
- 0
- Citations by year
- 2026: 4 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 9 · 2019: 6 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 10 · 2013: 11 · 2012: 11
- FWCI
- 4.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Planta Medica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences (N01-ES-25482)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
- Keywords
- herb-drug interactions, cytochrome P450 inhibition, P-glycoprotein, goldenseal, Ginkgo biloba, grape seeds, Silybum marianum, ginseng, ginsenosides, CYP3A4, CYP2C8, CYP2D6, CYP2C9, CYP2C19, CYP2E1, CYP1A2, hydrastine, ginsenoside Rh1, plant extracts, drug clearance
- MeSH terms
- Cytochrome P-450 Enzyme System, Panax, Humans, Male, Phytotherapy, Microsomes, Liver, Plant Extracts, Plants, Medicinal, Seeds, Plant Leaves, Plant Roots, Ginkgo biloba, Silybum marianum, Rhizome, Vitis, Hydrastis, Herb-Drug Interactions, In Vitro Techniques
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