Synergistic increases of metabolism and oxidation-reduction genes on
their expression after combined treatment with a CYP1A inducer and
andrographolide
Chatuphonprasert W, Jarukamjorn K, Kondo S, Nemoto N.
Department of Toxicology, Graduate School of Medicine and
Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama
930-0194 Japan; Academic Office for Pharmaceutical Sciences, Faculty
of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002
Thailand.
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 [PubMed - as supplied by publisher]
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