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Chem Biol Interact. 2009 Dec 10;182(2-3):233-8. doi: 10.1016/j.cbi.2009.09.001. Epub 2009 Sep 6.

Synergistic increases of metabolism and oxidation-reduction genes on their expression after combined treatment with a CYP1A inducer and andrographolide.

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1
Department of Toxicology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

Abstract

We previously reported that andrographolide greatly enhanced the expression of CYP1A1. Since andrographolide is a major constituent of Andrographis paniculata, which has been employed for centuries in Asia and Europe as a folk remedy, we further analyzed genes whose expression was modified by andrographolide using primary-cultured mouse hepatocytes in a microarray assay. With the threshold for modification set at 2-fold, andrographolide up-regulated 18 genes among 28,853 genes, most of them related to metabolism/oxidation/reduction. Meanwhile, 5 genes, related to protein binding or calcium ion binding, were down-regulated. A combination of beta-naphthoflavone (beta-NF), a CYP1A inducer, and andrographolide modified the expression of 45 genes (27 up-regulated and 18 down-regulated), although beta-NF single treatment up-regulated 4 genes. The affected genes were again mostly related to metabolism and oxidation-reduction. Among P450 isoforms, andrographolide by itself induced CYP1A1, CYP2A4, CYP2B9, and CYP2B10 expression. Synergistic expression of CYP1A1 and CYP1B1 mRNA was confirmed by quantitative RT-PCR. These observations suggest that drug interaction and risk assessment with the use of andrographolide or A. paniculata should be elucidated.

PMID:
19737545
DOI:
10.1016/j.cbi.2009.09.001
[Indexed for MEDLINE]

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