Renal vectorial transport of berberine mediated by organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins 1 (MATE1) in rats
Abstract
Abstract Berberine, a well‐known plant alkaloid derived from Rhizoma coptidis, has potential applications as a therapeutic drug for diabetic nephropathy. However, the transporter‐mediated renal transport of berberine remains largely unclear. This study aimed to investigate the renal transport mechanism of berberine using transfected cells, kidney slices and animal experiments. In Madin‐Darby canine kidney (MDCK) cells stably expressing rat OCT2 (MDCK‐rOCT2) and kidney slices, saturable and non‐saturable uptake of berberine was observed, and corticosterone could inhibit the uptake of berberine, with IC 50 values of 0.1 μ m and 147.9 μ m , respectively. In double‐transfected cells, the cellular accumulation of berberine into MDCK‐rOCT2 and MDCK‐rOCT2‐rMATE1 (MDCK cells stably expressing rOCT2 and rMATE1) cells was significantly higher than the uptake into MDCK cells. Meanwhile, berberine transcellular transport was considerably higher in double‐transfected MDCK‐rOCT2‐rMATE1 cells than in MDCK and MDCK‐rOCT2 cells. Corticosterone for MDCK‐rMATE1 and MDCK‐MDR1 and pyrimethamine for MDCK‐rMATE1 at high concentrations could inhibit the efflux of berberine. In animal experiments, compared with the berberine alone group, the cumulative urinary excretion of berberine significantly decreased in the corticosterone or pyrimethamine pretreatment groups. In the rat kidney, pyrimethamine increased, and a low dose of corticosterone (5 mg/kg) decreased, the berberine concentration. However, there was no apparent change in the renal concentration of berberine in rats pretreated with corticosterone (10 or 20 mg/kg). Thus, berberine is not only a substrate of OCT2 and P‐glycoprotein, but is also a substrate of MATE1. Both OCT2 and MATE1 mediate the renal vectorial transport of berberine.
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Low systemic exposure does not protect against interactions; rather, it shifts their site toward the absorption and elimination interfaces, where local concentrations are high.
“In summary, low systemic exposure does not protect against interactions; rather, it shifts their site toward the absorption and elimination interfaces, where local concentrations are high (Figure 1) [37,43,48].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [37]
Berberine is transported vectorially through OCT2 at the basolateral membrane and MATE1 at the apical membrane, and is a substrate of P-glycoprotein.
“At the renal level, berberine is transported vectorially through organic cation transporter 2 (OCT2) at the basolateral membrane and through multidrug and toxin extrusion protein 1 (MATE1) at the apical membrane, while also being a substrate of P-glycoprotein [37].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [37]
Berberine competes with cationic drugs eliminated by the same route.
“This dependence on organic cation transporters explains why berberine competes with cationic drugs eliminated by the same route [37,65].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [37]
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 [37]
Berberine is not a harmless "natural" product but an active pharmacological perpetrator, with an interaction profile predictable from its pharmacology.
“Berberine is not a harmless “natural” product but an active pharmacological perpetrator, with an interaction profile predictable from its pharmacology [35,37,111].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [37]
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“At the renal level, berberine is transported vectorially through organic cation transporter 2 (OCT2) at the basolateral membrane and through multidrug and toxin extrusion protein 1 (MATE1) at the apical membrane, while also being a substrate of P-glycoprotein [37].”
Influential
- Authors
- Shi, R., Yang, Y., Xu, Z., Dai, Y., Zheng, M., Wang, T., Li, Y., & Ma, Y.
- Affiliations
- Shanghai University of Traditional Chinese Medicine (CN)
- Corresponding author
- Ma, Yueming
- Venue
- Biopharmaceutics & Drug Disposition
- Publisher
- Wiley
- Published
- 2017-12-15
- Volume
- 39
- Issue
- 1
- Pages
- 47-58
- ISSN
- 0142-2782 (ISSN-L)
- 1099-081X
- OpenAlex
- W2766962095
- Cited by
- 14
- References
- 49
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 1
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biopharmaceutics & Drug Disposition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81273658, 81303296)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- berberine, organic cation transporter 2, MATE1, P-glycoprotein, corticosterone, pyrimethamine, renal excretion, diabetic nephropathy, Coptidis Rhizoma, drug transporters
- MeSH terms
- Organic Cation Transporter 2, Animals, Berberine, Biological Transport, Cells, Cultured, Corticosterone, Dogs, Drug Interactions, Kidney, Male, Pyrimethamine, Antiporters, Organic Cation Transport Proteins, Rats
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