The In Vitro Inhibition of Human CYP1A2, CYP2D6 and CYP3A4 by Tetrahydropalmatine, Neferine and Berberine
Abstract
The purpose of this study was to investigate the in vitro inhibition potential of the three purified herbal constituents tetrahydropalmatine (Tet), neferine (Nef) and berberine (Ber) towards recombinant human CYP1A2, CYP2D6 and CYP3A4 metabolic activities. In vitro incubations were performed with phenacetin, dextromethorphan and testosterone, respectively, as CYP substrates and their metabolites were determined by validated HPLC methods. Positive control inhibitors were run for each CYP in all incubation series. Inhibition was expressed by IC₅₀ values. All herbal constituents demonstrated some, but variable, inhibition potencies towards the investigated CYP enzymes. CYP2D6 was the most sensitive for inhibition and then mainly by Tet and Ber with IC₅₀ values of 3.04 ± 0.26 µM and 7.40 ± 0.36 µM, respectively. CYP3A4 and especially CYP1A2 were inhibited to a much smaller extent by all constituents. Neferine showed the lowest overall interaction potential towards the CYP enzymes investigated. The CYP inhibition potential for the purified constituents could be related to their chemical structures. No clinical significant metabolic interaction seems likely to occur between the CYP enzymes and herbal constituents tested, with a possible exception for the CYP2D6 inhibition by Tet and Ber.
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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 [69]
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 [69]
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Additional file 1 of Toxicity and toxicokinetics of the ethanol extract of Zuojin formula
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- Authors
- Zhao, Y., Hellum, B. H., Liang, A., & Nilsen, O. G.
- Affiliations
- Norwegian University of Science and Technology (NO)
- China Academy of Chinese Medical Sciences (CN)
- Corresponding author
- Zhao, Yong
- Venue
- Phytotherapy Research
- Publisher
- Wiley
- Published
- 2011-06-16
- Volume
- 26
- Issue
- 2
- Pages
- 277-283
- ISSN
- 0951-418X (ISSN-L)
- 1099-1573
- OpenAlex
- W2112625250
- Cited by
- 51
- References
- 24
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 8 · 2021: 1 · 2020: 4 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 7 · 2013: 3 · 2012: 5
- FWCI
- 5.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Phytotherapy Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Complementary and alternative medicine › Traditional Chinese Medicine Analysis
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- tetrahydropalmatine, neferine, berberine, CYP1A2 inhibition, CYP2D6 inhibition, CYP3A4 inhibition, cytochrome P450 inhibition, herbal constituents, phenacetin, dextromethorphan, testosterone, IC50, structure-inhibition relationship
- MeSH terms
- Berberine, Berberine Alkaloids, Enzyme Inhibitors, Humans, Plant Extracts, Molecular Structure, Inhibitory Concentration 50, Benzylisoquinolines, Cytochrome P-450 CYP1A2 Inhibitors, Cytochrome P-450 CYP2D6 Inhibitors, Cytochrome P-450 CYP3A Inhibitors
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