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Influence of Orally Administered Borneol on the Expression of Hepatic Transporters in Rats

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Abstract

Background and Objective

Borneol, a traditional Chinese medicine (TCM), is often orally co-administered with other TCM and chemical drugs, but the drug–drug interactions between borneol and the other compounds remains unclear. This work investigates the effect of orally administered borneol on the transcription and expression of hepatic uptake transporters (Ntcp, Oatp2b1, Oatp1a1, Oatp1a4, Oct1, Oct2, Octn2 and Oat2) and efflux transporters (Mdrla, Mrp2, Mrp4 and Mrp5) in rats, aiming to obtain essential information to guide its clinical applications.

Methods

Rats were administered borneol (33, 100 and 300 mg/kg/day, respectively) and vehicle (control) orally via intragastric gavage for 7 consecutive days. The mRNA levels of rat hepatic uptake transporters (Ntcp, Oatp2b1, Oatp1a1, Oatp1a4, Oct1, Oct2, Octn2 and Oat2) and efflux transporters (Mdrla, Mrp2, Mrp4 and Mrp5) were determined using real-time quantitative PCR, while the hepatic Ntcp, Mdrla, Mrp2, Mrp4 and Mrp5 proteins were quantified using western blotting.

Results

The oral administration of borneol led to dose-dependent inhibition of mRNA and protein expression of Mrp4 and Mdr1a, dose-independent inhibition of mRNA and protein expression of Mrp2, and inverse dose-dependent inhibition of mRNA and protein expression of Ntcp. No significant effects were observed for mRNA expression of the other transporters tested following borneol administration.

Conclusions

Oral administration of borneol may affect the metabolism of substances that are involved in bile acid enterohepatic circulation and substrates of Ntcp, Mdrla, Mrp2 and Mrp4 transporters.

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Author notes

  1. Lin Chen and Lu Liao contributed equally to this work and are co-first authors.

Authors and Affiliations

  1. Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei University, Wuhan, 430062, China

    Lin Chen, Lu Liao, Ting Zhai, Xiangtao Huang & Yong Chen

  2. School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China

    Lin Chen

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  1. Lin Chen
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Correspondence to Yong Chen.

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Funding

No funding was received to conduct this study.

Conflict of interest

Lin Chen, Lu Liao, Ting Zhai, Xiangtao Huang and Yong Chen declare that they have no conflict of interest.

Ethical approval

This study was approved by the Ethic Committee of Hubei University and complied with health guidelines for the care and use of laboratory animals.

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Chen, L., Liao, L., Zhai, T. et al. Influence of Orally Administered Borneol on the Expression of Hepatic Transporters in Rats. Eur J Drug Metab Pharmacokinet 44, 103–109 (2019). https://doi.org/10.1007/s13318-018-0499-1

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