Quasi-Irreversible Inhibition of CYP2D6 by Berberine
Open accessAbstract
In our previous study, Hwang-Ryun-Hae-Dok-Tang, which contains berberine (BBR) as a main active ingredient, inhibited cytochrome P450 (CYP) 2D6 in a quasi-irreversible manner. However, no information is available on the detailed mechanism of BBR-induced CYP2D6 inhibition. Thus, the present study aimed to characterize the inhibition mode and kinetics of BBR and its analogues against CYP2D6 using pooled human liver microsomes (HLM). BBR exhibited selective quasi-irreversible inhibition of CYP2D6 with inactivation rate constant (kinact) of 0.025 min−1, inhibition constant (KI) of 4.29 µM, and kinact/KI of 5.83 mL/min/µmol. In pooled HLM, BBR was metabolized to thalifendine (TFD), demethyleneberberine (DMB), M1 (proposed as demethylene-TFD), and to a lesser extent berberrubine (BRB), showing moderate metabolic stability with a half-life of 35.4 min and a microsomal intrinsic clearance of 7.82 µL/min/mg protein. However, unlike BBR, those metabolites (i.e., TFD, DMB, and BRB) were neither selective nor potent inhibitors of CYP2D6, based on comparison of half-maximal inhibitory concentration (IC50). Notably, TFD, but not DMB, exhibited metabolism-dependent CYP2D6 inhibition as in the case of BBR, which suggests that methylenedioxybenzene moiety of BBR may play a critical role in the quasi-irreversible inhibition. Moreover, the metabolic clearance of nebivolol (β-blocker; CYP2D6 substrate) was reduced in the presence of BBR. The present results warrant further evaluation of BBR–drug interactions in clinical situations.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Berberine inhibits CYP2D6 and CYP2C9 quasi-irreversibly through a metabolite-intermediate complex.
“with CYP2D6/CYP2C9 inhibition that is quasi-irreversible through a metabolite-intermediate complex”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [59]
Results §3.4 and the Discussion support quasi-irreversible CYP2D6 inhibition by berberine and link it to a possible metabolite-intermediate complex. But Results §3.1 explicitly says CYP2C9 was not markedly inhibited by berberine; the paper does not establish the claimed mechanism for CYP2C9. (LLM, conf=0.90)
Experimental — accuracy not yet measuredHow long CYP2D6 activity stays suppressed in humans after berberine is stopped has not been measured; the clinical duration of this component is inferred from the in vitro mechanism and not observed.
“What nobody has measured is how long CYP2D6 activity stays suppressed in humans after berberine is stopped, which means the clinical duration of this component is inferred from the in vitro mechanism and not observed [35,59].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [59]
The Results (section 3.4; page unavailable) measure reversibility in human liver microsomes, not how long CYP2D6 suppression persists in people after berberine is stopped. The Discussion and Conclusions call for further clinical evaluation, supporting the distinction between the observed in vitro mechanism and unobserved clinical duration. The paper does not establish the broader assertion that nobody has measured post-discontinuation suppression in humans. (LLM, conf=0.83)
Experimental — accuracy not yet measuredBerberine and its metabolites are themselves substrates and/or inhibitors of several enzymes and transporters, broadening the spectrum of interactions.
“Berberine and its metabolites (berberrubine, thalifendine, demethyleneberberine, and jatrorrhizine), formed predominantly by CYP1A2, CYP2D6 and CYP3A4, are themselves substrates and/or inhibitors of several enzymes and transporters, which broadens the spectrum of interactions [59,60,61].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [59]
The Introduction (page not specified) identifies the four metabolites and reports that CYP1A2, CYP2D6 and CYP3A4 metabolize berberine to thalifendine and demethyleneberberine. Results §3.1 and §3.3 (pages not specified) show that berberine inhibits CYP2D6 and its named metabolites inhibit several CYP enzymes. The paper does not establish that berberine or those metabolites are substrates or inhibitors of transporters, so that part of the attributed claim is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredChronic, repeated administration of berberine lets inhibitory effects accumulate and carries a time-dependent component of CYP2D6 inhibition.
“Chronic, repeated administration, typical of supplement use, lets these inhibitory effects accumulate, and it carries a time-dependent component of CYP2D6 inhibition that we characterize in Section 2.2.1 [35,59].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [59]
The Discussion reports time-dependent, metabolism-dependent CYP2D6 inhibition by berberine. The Conclusions say repeated administration of a quasi-irreversible inhibitor *can* lead to its accumulation, but do not show that chronic berberine use causes inhibitory effects to accumulate in people. That part of the claim presents a possibility as an established effect. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe contribution of quasi-irreversible CYP2D6 inhibition, the balance between CYP3A4 inhibition and PXR-mediated induction, the concentration-response relationship for that induction and the time at which it begins, and the duration of both effects after berberine is stopped all need to be quantified in humans; at present each is extrapolated from in vitro systems.
“The contribution of quasi-irreversible CYP2D6 inhibition, the balance between CYP3A4 inhibition and PXR-mediated induction, the concentration–response relationship for that induction and the time at which it begins, and the duration of both effects after berberine is stopped, all need to be quantified in humans; at present each is extrapolated from in vitro systems [59,75].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [59]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Low systemic exposure to berberine coexists with high local concentrations that inhibit CYP3A4/CYP2D6/CYP2C9, can induce CYP3A4 transcriptionally, and modulate P-glycoprotein and organic cation transporters.
“Low systemic exposure coexists with high local concentrations that inhibit CYP3A4/CYP2D6/CYP2C9, and can even induce CYP3A4 transcriptionally, and that modulate P-glycoprotein and organic cation transporters [35,59,65]”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [59]
The Results (section 3.1; page not available) show that berberine inhibits CYP2D6 in human liver microsomes. They also say CYP2C9 and CYP3A4 were not markedly inhibited, contrary to that part of the claim. The passages found do not establish the low-systemic/high-local exposure contrast, transcriptional CYP3A4 induction, or modulation of P-glycoprotein and organic cation transporters. (LLM, conf=0.89)
Experimental — accuracy not yet measuredCYP2D6 inhibition by berberine is quasi-irreversible, develops in a time-, concentration-, and NADPH-dependent manner, and is attributed to formation of a metabolite-intermediate complex with the heme iron.
“CYP2D6 inhibition is quasi-irreversible in the strict pharmacological sense rather than simply long-lasting, and the primary source describes it as such: the effect develops in a time-, concentration-, and NADPH-dependent manner and is attributed to formation of a metabolite-intermediate complex (MIC) with the heme iron [59].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [59]
Temporal separation of administration reduces, but does not eliminate, absorption-level interactions and has no effect on systemic enzyme inhibition.
“Third, temporal separation of administration reduces, but does not eliminate, absorption-level interactions and has no effect on systemic enzyme inhibition [54,59].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [59]
The Conclusions (page unavailable) report quasi-irreversible CYP2D6 inhibition by berberine, but do not address the effect of separating administration times. Searches for dosing intervals and absorption-level interactions found no passage testing or discussing whether temporal separation reduces absorption interactions or leaves enzyme inhibition unchanged. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Dresser, G. K., Spence, J. D., & Bailey, D. G. (2000) · Clinical Pharmacokinetics · doi:10.2165/00003088-200038010-00003 · Cited by 908 · see citing works
Bjornsson, T. D., Callaghan, J. T., Einolf, H. J., Fischer, V., Gan, L. L., Grimm, S. W., Kao, J., King, S. P., Miwa, G. T., Ni, L., et al. (2003) · Drug Metabolism and Disposition · doi:10.1124/dmd.31.7.815 · Cited by 792 · see citing works
Role of Pharmacokinetics and Metabolism in Drug Discovery and Development
Lin, J. H., & Lu, A. Y. H. (1997) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01340-1 · Cited by 713 · see citing works
The anti-inflammatory potential of berberine in vitro and in vivo
Kuo, C.-L., Chi, C., & Liu, T. (2003) · Cancer Letters · doi:10.1016/j.canlet.2003.09.002 · Cited by 686 · see citing works
Harmless Herbs? A Review of the Recent Literature
Ernst, E. (1998) · The American Journal of Medicine · doi:10.1016/s0002-9343(97)00397-5 · Cited by 632 · see citing works
Obach, R. S., Walsky, R. L., & Venkatakrishnan, K. (2006) · Drug Metabolism and Disposition · doi:10.1124/dmd.106.012633 · Cited by 463 · see citing works
Zhang, H., Wei, J., Xue, R., Wu, J.-D., Zhao, W., Wang, Z., Wang, S., Zhou, Z.-X., Song, D., Wang, Y., et al. (2009) · Metabolism · doi:10.1016/j.metabol.2009.07.029 · Cited by 442 · see citing works
Berberine sulfate: antimicrobial activity, bioassay, and mode of action
Amin, A., Subbaiah, T. V., & Abbasi, K. M. (1969) · Canadian Journal of Microbiology · doi:10.1139/m69-190 · Cited by 299 · see citing works
Cardiovascular actions of berberine
Lau, C., Yao, X., Chen, Z., Ko, W., & Huang, Y. (2001) · Cardiovascular Drug Reviews · doi:10.1111/j.1527-3466.2001.tb00068.x · Cited by 281 · see citing works
Bertelsen, K. M., Venkatakrishnan, K., Moltke, L. L., Obach, R. S., & Greenblatt, D. J. (2003) · Drug Metabolism and Disposition · doi:10.1124/dmd.31.3.289 · Cited by 279 · see citing works
Orr, S. T. M., Ripp, S. L., Ballard, T. E., Henderson, J. L., Scott, D. O., Obach, R. S., Sun, H., & Kalgutkar, A. S. S. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm300065h · Cited by 230 · see citing works
Antimicrobial properties of berberines alkaloids in Coptis chinensis Franch by microcalorimetry
Yan, D., Jin, C. S., Xiao, X., & Dong, X. (2007) · Journal of Biochemical and Biophysical Methods · doi:10.1016/j.jbbm.2007.07.009 · Cited by 186 · see citing works
Antiviral activity of berberine and related compounds against human cytomegalovirus
Hayashi, K., Minoda, K., Nagaoka, Y., Hayashi, T., & Uesato, S. (2007) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2006.12.085 · Cited by 165 · see citing works
Sack, R. B., & Froehlich, J. L. (1982) · Infection and Immunity · doi:10.1128/iai.35.2.471-475.1982 · Cited by 158 · see citing works
Kim, M., Kim, H., Cha, I., Park, J.-S., Shon, J., Liu, K., & Shin, J. (2005) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.2110 · Cited by 152 · see citing works
Self-citationSerafim, T. L., Oliveira, P. J., Sardão, V. A., Perkins, E., Parke, D., & Holy, J. M. (2007) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-007-0558-9 · Cited by 130 · see citing works
Lee, C.-H., Chen, J., Hsiang, C., Wu, S., Wu, H.-C., & Ho, T. (2007) · Pharmacological Research · doi:10.1016/j.phrs.2007.06.003 · Cited by 129 · see citing works
Neuropharmacological and pharmacokinetic properties of berberine: a review of recent research
Ye, M., Fu, S., Pi, R., & He, F. (2009) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.61.07.0001 · Cited by 127 · see citing works
Neuropharmacological and pharmacokinetic properties of berberine: a review of recent research
Ye, M., Fu, S., Pi, R., & He, F. (2009) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp/61.07.0001 · Cited by 124 · see citing works
Isolation and Identification of Urinary Metabolites of Berberine in Rats and Humans
Qiu, F., Zhu, Z., Kang, N., Piao, S., Qin, G., & Yao, X. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.108.021659 · Cited by 120 · see citing works
Rojsanga, P., Sukhthankar, M., Gritsanapan, W., & Baek, S. J. (2007) · Cancer Letters · doi:10.1016/j.canlet.2007.09.007 · Cited by 113 · see citing works
Bioactivities of berberine metabolites after transformation through CYP450 isoenzymes
Li, Y., Ren, G., Wang, Y.-X., Kong, W.-J., Yang, P., Wang, Y.-M., Li, Y.-H., Yi, H., Li, Z.-R., Song, D.-Q., et al. (2011) · Journal of Translational Medicine · doi:10.1186/1479-5876-9-62 · Cited by 109 · see citing works
Elmer, G. W., Lafferty, W. E., Tyree, P. T., & Lind, B. K. (2007) · Annals of Pharmacotherapy · doi:10.1345/aph.1k221 · Cited by 90 · see citing works
Shaikh, A. S., Thomas, A. B., & Chitlange, S. S. (2020) · Phytotherapy Research · doi:10.1002/ptr.6585 · Cited by 90 · see citing works
Perloff, E. S., Mason, A. K., Dehal, S. S., Blanchard, A. P., Morgan, L., Ho, T., Dandeneau, A. A., Crocker, R. M., Chandler, C., Boily, N., et al. (2009) · Xenobiotica · doi:10.1080/00498250802638155 · Cited by 88 · see citing works
Enzyme Kinetics for Clinically Relevant CYP Inhibition
Zhang, Z., & Wong, Y. (2005) · Current Drug Metabolism · doi:10.2174/1389200054021834 · Cited by 82 · see citing works
Lee, K. S., & Kim, S. K. (2011) · Journal of Applied Toxicology · doi:10.1002/jat.1720 · Cited by 81 · see citing works
Self-citationTaylor, C. E., & Greenough, W. B. (1989) · Annual Review of Public Health · doi:10.1146/annurev.pu.10.050189.001253 · Cited by 71 · see citing works
VandenBrink, B. M., & Isoherranen, N. (2010) · PubMed · Cited by 69 · see citing works
Alolga, R. N., Fan, Y., Chen, Z., Liu, L., Zhao, Y., Li, J., Chen, Y., Lai, M., Li, P., & Qi, L. (2016) · Scientific Reports · doi:10.1038/srep27671 · Cited by 57 · see citing works
Zhao, Y., Hellum, B. H., Liang, A., & Nilsen, O. G. (2012) · Phytotherapy Research · doi:10.1002/ptr.3554 · Cited by 51 · see citing works
Freston, J. W., Chiu, Y. ‐., Mulford, D. J., & Ballard, E. D., II (2003) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.2003.01455.x · Cited by 47 · see citing works
Berberine inhibits WEHI-3 leukemia cells in vivo.
Yu, F.-S., Yang, J., Lin, H.-J., Yu, C.-S., Tan, T., Lin, Y.-T., Lin, C.-C., Lu, H. F., & Chung, J. (2007) · PubMed · Cited by 47 · see citing works
Berberine and chloramphenicol in the treatment of cholera and severe diarrhoea.
Lahiri, S., & Dutta, N. K. (1967) · PubMed · Cited by 47 · see citing works
Koppen, L. M., Whitaker, A., Rosene, A., & Beckett, R. D. (2017) · Journal of Evidence-Based Complementary & Alternative Medicine · doi:10.1177/2156587216687695 · Cited by 47 · see citing works
Effects of Berberine on Delayed Afterdepolarizations in Ventricular Muscles In Vitro and In Vivo
Wang, Y.-X., Yao, X. J., & Tan, Y.-H. (1994) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199405000-00005 · Cited by 41 · see citing works
Assessment of drug–drug interactions caused by metabolism-dependent cytochrome P450 inhibition
Lee, J.-Y., Lee, S. Y., Oh, S. J., Lee, K., Jung, Y. S., & Kim, S. K. (2012) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2012.05.007 · Cited by 40 · see citing works
Self-citationTumor-specific cytotoxicity and apoptosis-inducing activity of berberines.
Inoue, K., Kulsum, U., Chowdhury, S. A., Fujisawa, S., Ishihara, M., Yokoe, I., & Sakagami, H. (2005) · PubMed · Cited by 39 · see citing works
Evaluation of 24 CYP2D6 Variants on the Metabolism of Nebivolol In Vitro
Hu, X., Lan, T., Dai, D., Xu, R.-A., Yuan, L., Zhou, Q., Li, Y., Cai, J., & Hu, G. (2016) · Drug Metabolism and Disposition · doi:10.1124/dmd.116.071811 · Cited by 18 · see citing works
Levy, R. H., Hachad, H., Yao, C., & Ragueneau, I. (2003) · Current Drug Metabolism · doi:10.2174/1389200033489325 · Cited by 16 · see citing works
Inhibitory effects of Hwang-Ryun-Hae-Dok-Tang on cytochrome P450 in human liver microsomes
Lee, S. Y., Jang, H., Lee, J.-Y., Yeul, J., Oh, S. J., & Kim, S. K. (2014) · Xenobiotica · doi:10.3109/00498254.2014.953624 · Cited by 16 · see citing works
Self-citationWatanabe, A., Takakusa, H., Kimura, T., Inoue, S.-I., Kusuhara, H., & Ando, O. (2016) · Drug Metabolism and Disposition · doi:10.1124/dmd.116.071654 · Cited by 11 · see citing works
Metabolic characterization of meso-dihydroguaiaretic acid in liver microsomes and in mice.
Jeon, J. S., Oh, S., Lee, J.-Y., Ryu, C., Kim, Y.-M., Lee, B. H., & Kim, S. K. (2015) · Food and Chemical Toxicology · doi:10.1016/j.fct.2014.12.007 · Cited by 10 · see citing works
Self-citationReinen, J., Smit, M., & Wenker, M. (2018) · European Journal of Drug Metabolism and Pharmacokinetics · doi:10.1007/s13318-018-0485-7 · Cited by 4 · see citing works
Discovery of rubiarbonone C as a selective inhibitor of cytochrome P450 4F enzymes
Choi, Y. J., Quan, K. T., Park, I., Lee, S. J., Kang, K. W., Na, M., & Kim, S. K. (2018) · Archives of Toxicology · doi:10.1007/s00204-018-2315-8 · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
2 of the 47 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Enzyme Activity of Natural Products on Cytochrome P450
Zuo, H., Huang, H., Lin, Y.-C.-D., Cai, X., Kong, X., Luo, D.-L., Zhou, Y.-H., & Huang, H. (2022) · Molecules · doi:10.3390/molecules27020515 · Cited by 64 · see citing works
Herb-Drug Interactions and Their Impact on Pharmacokinetics: An Update
Cheng, W., Xia, K., Wu, S., & Li, Y. (2023) · Current Drug Metabolism · doi:10.2174/1389200224666230116113240 · Cited by 49 · see citing works
Zhang, F., Liu, W., Huang, J., Chen, Q., Wang, D., Zou, L., Zhao, Y., Zhang, W., Xu, J., Chen, H., et al. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00697-2 · Cited by 35 · see citing works
Gajula, S. N. R., Pillai, M. S., Samanthula, G., & Sonti, R. (2021) · Bioanalysis · doi:10.4155/bio-2021-0132 · Cited by 34 · see citing works
Effects of Berberis vulgaris, and its active constituent berberine on cytochrome P450: a review
Bathaei, P., Imenshahidi, M., & Hosseinzadeh, H. (2024) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-024-03326-x · Cited by 29 · see citing works
Pharmacokinetic Drug–Drug Interactions and Herb–Drug Interactions
Choi, M., & Song, I. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13050610 · Cited by 21 · see citing works
Zhao, Y., Liu, P., Zhang, Y., Jiang, H., Luan, H., Ying-mei, X., Zhang, Y., & Li, R. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109319 · Cited by 17 · see citing works
Li, G., Zhao, M., & Zhao, L. (2021) · Arabian Journal of Chemistry · doi:10.1016/j.arabjc.2021.103562 · Cited by 9 · see citing works
Inactivation of CYP2D6 by Berberrubine and the Chemical Mechanism
Rao, J., Wang, T., Yu, L., Wang, K., & Qiu, F. (2024) · Biochemistry · doi:10.1021/acs.biochem.4c00450 · Cited by 6 · see citing works
Kondža, M., Bukić, J., Ćavar, I., & Tubić, B. (2025) · Drugs and Drug Candidates · doi:10.3390/ddc4020024 · Cited by 5 · see citing works
Cytochrome P450 in GtoPdb v.2023.1
Burns, K. E., & Helsby, N. A. (2023) · IUPHAR/BPS Guide to Pharmacology CITE · doi:10.2218/gtopdb/f242/2023.1 · Cited by 4 · see citing works
Wang, J., Lu, S., Zhang, C., Wang, J., Wu, H., & Li, G. (2025) · Drug Design Development and Therapy · doi:10.2147/dddt.s491446 · Cited by 4 · see citing works
Cytochrome P450 in GtoPdb v.2021.2
Burns, K. E., & Helsby, N. A. (2021) · IUPHAR/BPS Guide to Pharmacology CITE · doi:10.2218/gtopdb/f242/2021.2 · Cited by 3 · see citing works
Harnessing the Anticancer Potential of Plant Alkaloids Through Green Extraction Technologies
Bouissane, L., Khatib, S., Boukhari, R. E., Thiéry, V., & Fatimi, A. (2026) · Applied Biosciences · doi:10.3390/applbiosci5020023 · Cited by 2 · see citing works
Yu, J., Ryu, J. H., Chi, Y. H., Paik, S. H., & Kim, S. K. (2024) · Toxicology in Vitro · doi:10.1016/j.tiv.2024.105922 · Cited by 2 · see citing works
Self-citationLiu, Y., Lawless, M. S., Roe, A. L., & Ferguson, S. S. (2025) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2025.117385 · Cited by 2 · see citing works
Dumitru, C. N., Marcu, T., Dumitru, A. O., Tudor, S. S., Ferțu, I. D., Elisei, A.-M., & Goroftei, L. (2026) · Pharmaceuticals · doi:10.3390/ph19081313 · Cited by 2 · see citing works
“…local concentrations that inhibit CYP3A4/CYP2D6/CYP2C9, and can even induce CYP3A4 transcriptionally, and that modulate P-glycoprotein and organic cation transporters [35,59,65]; superimposed on these are additive pharmacodynamic effects, including hERG-channel block with QT prolongation [39,84].”
InfluentialMareş, C., PĂUN, A. M., Mernea, M., Tatarus, S.-N., Cristea, B. M., Marinaș, I. C., & Avram, S. (2026) · Processes · doi:10.3390/pr14071099 · Cited by 1 · see citing works
Bioactivation and reactivity research advances—2024 year in review
Liu, J., Argikar, U. A., Brunetti, P., Chatzopoulou, M., Chen, L., Cho, S., Hauri, S., Kramlinger, V. M., Lang, J., Ma, B., et al. (2025) · Drug Metabolism Reviews · doi:10.1080/03602532.2025.2530407
Self-citationBioactivation and reactivity research advances – 2025 year in review
Liu, J., Argikar, U. A., Brunetti, P., Chatzopoulou, M., Cho, S., Claesson, A., Dhaware, D., Lang, J., Ma, B., Ma, S., et al. (2026) · Drug Metabolism Reviews · doi:10.1080/03602532.2026.2705851
Self-citation
- Authors
- Kim, H. G., Lee, H. S., Jeon, J. S., Choi, Y. J., Choi, Y. J., Yoo, S.-Y., Kim, E.-Y., Lee, K., Park, I., Na, M., Park, H.-J., Cho, S.-W., Kim, J.-H., Lee, J.-Y., & Kim, S. K.
- Affiliations
- Chungnam National University (KR)
- Korea University (KR)
- Korea Institute of Toxicology (KR)
- Yonsei University (KR)
- Corresponding author
- Lee, Jae-Young
- Kim, Sang Kyum
- ORCID
- Venue
- Pharmaceutics
- Publisher
- MDPI AG
- Published
- 2020-09-24
- Volume
- 12
- Issue
- 10
- Pages
- 916
- ISSN
- 1999-4923 (ISSN-L)
- PMC
- PMC7600264
- OpenAlex
- W3088303855
- Cited by
- 21
- References
- 47
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 5
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Pharmaceutics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- National Research Foundation of Korea (NRF-2018M3A9H1021640, NRF-2018R1C1B6005379)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- berberine, CYP2D6 inhibition, berberrubine, drug metabolism, drug-drug interactions, nebivolol, cytochrome P450, herbal medicine
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
