Effects of berberine and hwangryunhaedok-tang on oral bioavailability and pharmacokinetics of ciprofloxacin in rats
Open accessAbstract
Hwangryunhaedok-Tang (HR) and berberine-containing single herbs are used to treat bacterial infection and inflammatory diseases in eastern Asia. The combination of berberine-containing herbal medicines and ciprofloxacin can be an excellent antibacterial chemotherapy against multidrug resistance bacteria. To evaluate the pretreatment effect of berberine and HR, vehicle, berberine (25 and 50 mg/kg/day), and HR (1.4 g/kg/day) were daily administered to rats for five consecutive days. On day 6, ciprofloxacin was administered (10 mg/kg, i.v. and 20 mg/kg, p.o.) to rats. To assess cotreatment effect of berberine and ciprofloxacin, berberine (50 mg/kg) and ciprofloxacin (20 mg/kg) were coadministered by single oral gavage. Pharmacokinetic data were estimated by noncompartmental model. Compared with ciprofloxacin alone (control group), coadministration of berberine (50 mg/kg) and ciprofloxacin significantly decreased C(max) of ciprofloxacin (P < 0.05). In addition, the pretreatment of berberine (50 mg/kg/day) and HR (1.4 g/kg/day) significantly decreased C(max) and AUC(0→∞), compared with control group (P < 0.05). The oral bioavailability of ciprofloxacin was reduced by cotreatment of berberine and pretreatment of berberine and HR. Our results suggest that the expression of P-glycoprotein and organic anion and/or organic cation transporters (OAT/OCT) could take a role in reduced oral bioavailability of ciprofloxacin by berberine and HR.
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Berberine also reduced the oral bioavailability of ciprofloxacin in animal models, suggesting involvement of organic anion/cation transporters.
“Berberine also reduced the oral bioavailability of ciprofloxacin in animal models, suggesting involvement of organic anion/cation transporters [78].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [78]
Berberine is both a substrate and an inhibitor of P-glycoprotein and can increase the intestinal absorption of its substrates.
“Berberine is both a substrate and an inhibitor of P-glycoprotein (P-gp/MDR1), and can increase the intestinal absorption of its substrates [58,77,78]”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [78]
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Cites
Efficacy of berberine in patients with type 2 diabetes mellitus
Yin, J., Xing, H., & Ye, J. (2008) · Metabolism · doi:10.1016/j.metabol.2008.01.013 · Cited by 801 · see citing works
Stermitz, F. R., Lorenz, P., Tawara, J. N., Zenewicz, L. A., & Lewis, K. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.030540597 · Cited by 763 · see citing works
Hu, Z., Yang, X., Ho, P. C., Chan, S. Y., Heng, P. W. S., Chan, E., Duan, W., Koh, H., & Zhou, S. (2005) · Drugs · doi:10.2165/00003495-200565090-00005 · Cited by 664 · see citing works
Bacterial efflux pump inhibitors from natural sources
Stavri, M., Piddock, L. J. V., & Gibbons, S. (2006) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkl460 · Cited by 547 · see citing works
Berberine: a potential phytochemical with multispectrum therapeutic activities
Vuddanda, P. R., Chakraborty, S., & Singh, S. (2010) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2010.517745 · Cited by 317 · see citing works
Zuo, F., Nakamura, N., Akao, T., & Hattori, M. (2006) · Drug Metabolism and Disposition · doi:10.1124/dmd.106.011361 · Cited by 284 · see citing works
Jayaraman, P., Sakharkar, M. K., Lim, C. S., Tang, T. H., & Sakharkar, K. R. (2010) · International Journal of Biological Sciences · doi:10.7150/ijbs.6.556 · Cited by 241 · see citing works
Efferth, T., Davey, M. W., Olbrich, A., et al. (2002) · Blood Cells Molecules and Diseases · doi:10.1006/bcmd.2002.0492 · Cited by 224 · see citing works
Lu, T., Song, J., Huang, F., et al. (2006) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2006.09.036 · Cited by 178 · see citing works
HEPATOBILIARY EXCRETION OF BERBERINE
Tsai, P.-L., & Tsai, T. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.32.4.405 · Cited by 160 · see citing works
Repeated administration of berberine inhibits cytochromes P450 in humans
Guo, Y., Chen, Y., Tan, Z.-R., Klaassen, C. D., & Zhou, H.-H. (2012) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-011-1108-2 · Cited by 137 · see citing works
P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers
Maeng, H.-J., Yoo, H.-J., Kim, I.-W., Song, I.-S., Chung, S.-J., & Shim, C.-K. (2002) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.10268 · Cited by 128 · see citing works
Berberine: Alkaloid with wide spectrum of pharmacological activities
Singh, A., Duggal, S., Kaur, N., & Singh, J. (2010) · Cited by 118 · see citing works
Seral, C. (2003) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkg223 · Cited by 115 · see citing works
Zhang, X., Qiu, F., Jiang, J. C., Gao, C., & Tan, Y. (2011) · Xenobiotica · doi:10.3109/00498254.2010.529180 · Cited by 109 · see citing works
Lin, H.-L., Liu, T.-Y., Wu, C.-W., & Chi, C.-W. (1999) · British Journal of Cancer · doi:10.1038/sj.bjc.6690710 · Cited by 100 · see citing works
Hwang, Y. S., Shin, C. Y., Huh, Y., et al. (2002) · Life Sciences · doi:10.1016/s0024-3205(02)01920-3 · Cited by 97 · see citing works
Self-citationFan, L., Zhang, W., Guo, D., Tan, Z.-R., Xu, P., Li, Q., Liu, Y.-Z., Zhang, L., He, T.-Y., Hu, D.-L., et al. (2007) · Clinical Pharmacology & Therapeutics · doi:10.1038/sj.clpt.6100318 · Cited by 81 · see citing works
Severina, I. I., Muntyan, M. S., Lewis, K., & Skulachev, V. P. (2001) · IUBMB Life · doi:10.1080/152165401317291183 · Cited by 76 · see citing works
Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco‐2) cells
Cavet, M. E., West, M., & Simmons, N. L. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701302 · Cited by 67 · see citing works
Health need and the use of alternative medicine among adults who do not use conventional medicine
Nahin, R. L., Dahlhamer, J. M., & Stussman, B. J. (2010) · BMC Health Services Research · doi:10.1186/1472-6963-10-220 · Cited by 65 · see citing works
Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp
Qiu, W., Jiang, X. H., Liu, C. X., Ju, Y., & Jin, J. X. (2009) · Phytotherapy Research · doi:10.1002/ptr.2808 · Cited by 64 · see citing works
Li, C., Kim, M.-H., Choi, H.-S., et al. (2011) · Archives of Pharmacal Research · doi:10.1007/s12272-011-1117-9 · Cited by 62 · see citing works
Active intestinal elimination of ciprofloxacin in rats: modulation by different substrates
Dautrey, S., Felice, K. P., Petiet, A., et al. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702703 · Cited by 60 · see citing works
Natural approaches to prevention and treatment of infections of the lower urinary tract.
Head, K. A. (2008) · PubMed · Cited by 59 · see citing works
Lin, H.-L., Liu, T., Lui, W., & Chi, C. (1999) · Cancer · doi:10.1002/(sici)1097-0142(19990501)85:9 · Cited by 57 · see citing works
Ciprofloxacin permeability and its active secretion through rat small intestine in vitro
Žakelj, S., STURM, K., & Kristl, A. (2006) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2006.02.004 · Cited by 54 · see citing works
Human MDR1 and MRP1 Recognize Berberine as Their Transport Substrate
Shitan, N., Tanaka, M., TERAI, K., Ueda, K., & Yazaki, K. (2007) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.60441 · Cited by 45 · see citing works
Pharmacokinetics of quinolones in renal insufficiency
Fillastre, J. P., Leroy, A., Moulin, B., et al. (1990) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/26.suppl_b.51 · Cited by 44 · see citing works
Lai, M.-Y., Hsiu, S., Hou, Y., et al. (2004) · Planta Medica · doi:10.1055/s-2004-815489 · Cited by 42 · see citing works
Is Ciprofloxacin a Substrate of P‐glycoprotein?
Park, M. S., Okochi, H., & Benet, L. Z. (2010) · Archives of Drug Information · doi:10.1111/j.1753-5174.2010.00032.x · Cited by 36 · see citing works
Thorburn, C. E. (2001) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/48.1.15 · Cited by 33 · see citing works
Influence of Renal Failure on Ciprofloxacin Pharmacokinetics in Rats
Nouaille-Degorce, B., Veau, C., Dautrey, S., Tod, M. M., Laouari, D., Carbon, C., & Farinotti, R. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.2.289 · Cited by 31 · see citing works
Berberine in toxin‐induced experimental cholera
Dutta, N. K., MARKER, P. H., & RAO, N. R. (1972) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1972.tb07247.x · Cited by 28 · see citing works
Herb-Drug Interactions: Focus on Pharmacokinetics
Cott, J. M. (2001) · CNS Spectrums · doi:10.1017/s1092852900001644 · Cited by 22 · see citing works
Suzuki, H., Tanabe, H., Mizukami, H., & Inoue, M. (2010) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.33.677 · Cited by 21 · see citing works
Hwang, Y., Kim, T. S., Cho, W., et al. (2012) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2012.04.032 · Cited by 18 · see citing works
Self-citationChen, Y., & Jun, P. (2000) · The Chinese Journal of Clinical Pharmacology · Cited by 16 · see citing works
The PK/PD index (CMAX/MIC) for ciprofloxacin in patients with cystic fibrosis.
Szałek, E., Kamińska, A., Goździk-Spychalska, J., et al. (2011) · PubMed · Cited by 15 · see citing works
Effect of Huang-Lian-Jie-Du-Decoction on pharmacokinetics of verapamil in rats
Xie, S., Hu, N., Jing, X., Liu, X., Xie, L. Y., Wang, G., & Liu, C. (2010) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.62.04.0005 · Cited by 12 · see citing works
Joyanes, P., Pascual, Á., Giménez, M.-J., et al. (2001) · Chemotherapy · doi:10.1159/000048551 · Cited by 9 · see citing works
Pharmacokinetic interaction of ketoconazole and itraconazole with ciprofloxacin
Abou‐Auda, H. S., Mustafa, A., & Al-Humayyd, M. S. (2007) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.586 · Cited by 8 · see citing works
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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
“Berberine also reduced the oral bioavailability of ciprofloxacin in animal models, suggesting involvement of organic anion/cation transporters [78].”
- Authors
- Hwang, Y.-H., Cho, W.-K., Jang, D., Ha, J.-H., Jung, K., Yun, H.-I., & Ma, J. Y.
- Affiliations
- Korea Institute of Oriental Medicine (KR)
- Chungnam National University (KR)
- KM-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea
- Venue
- Evidence-Based Complementary and Alternative Medicine
- Publisher
- Wiley
- Published
- 2012
- Volume
- 2012
- Pages
- 1-7
- ISSN
- 1741-427X (ISSN-L)
- 1741-4288
- PMC
- PMC3487491
- OpenAlex
- W2134268367
- Cited by
- 18
- References
- 42
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 1 · 2021: 1 · 2019: 1 · 2018: 3 · 2016: 2 · 2015: 2 · 2014: 1
- FWCI
- 0.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Evidence-based Complementary and Alternative Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Korea Institute of Oriental Medicine (K12050)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Keywords
- berberine, Hwangryunhaedok-tang, ciprofloxacin, oral bioavailability, pharmacokinetics, drug-drug interactions, P-glycoprotein, organic anion transporters, organic cation transporters, herbal medicine, antibacterial chemotherapy
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