4.2 Article

Effects of 27 natural products on drug metabolism genes in channel catfish (Ictalurus punctatus) cell line

Journal

XENOBIOTICA
Volume 50, Issue 9, Pages 1043-1051

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/00498254.2020.1737760

Keywords

Natural products; pregnane X receptor; cytochrome P450; in vitro; multi-drug resistance 1

Funding

  1. National Key R&D Program of China [2017YFC1600704]
  2. China Agricultural Research System [CARS-46]

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Pregnane X receptor (PXR) as a ligand dependent transcription factor, is capable of regulating gene expression of cytochromes P450 and transporters involved in xenobiotic/drug metabolism and elimination. Due to the species differences in the regulatory specificity of PXR, gene regulation should not be extrapolated from mammal to fish without research data. The aim of present study was to investigate the effect of 27 natural products on PXR, CYP3A30 and MDR1 genes in channel catfish (Ietalurus punetaus) kidney cells (CC-K). The results showed that bisdemethoxycurcumin, glycyrrhetnic acid, rotenone, artemisinin, dihydroartemisinin, ligustilide and matrine strongly induced the mRNA levels of PXR. Additionally, the up-regulation of CYP3A30 gene ran parallel with PXR gene after the treatment of demethoxycurcumin, glycyrrhetnic acid, artemisinin, matrine, baicalein, schisantherin A, ligustilide, and dihydroartemisinin. Moreover, we found that natural products schisandrin A, schisandrin B, schisandrol A, and schisandrol B significantly up-regulated the mRNA level of MDR1 gene. Our work with a view to provide experimental data support for further research, which will make for the rational application of natural products in channel catfish, such as to avoid adverse herb-drug interactions or accelerating the residue elimination of chemical medicine.

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