期刊
DRUG METABOLISM AND PHARMACOKINETICS
卷 31, 期 2, 页码 139-145出版社
JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.1016/j.dmpk.2016.01.002
关键词
AhR activator; Indirubin; CYP3A4 induction; PXR; Herb-drug interactions
资金
- Health and Labour Sciences Research Grant for Research on Food Safety from Ministry of Health, Labour and Welfare, Japan [22230301]
- Grants-in-Aid for Scientific Research [25460195] Funding Source: KAKEN
Ban-Lan-Gen is the common name for the dried roots of indigo plants, including Polygonum tinctorium, Isatis indigotica, Isatis tinctoria, and Strobilanthes cusia. Ban-Lan-Gen is frequently used as an anti-inflammatory and an anti-viral for the treatment of hepatitis, influenza, and various types of inflammation. One of the cytochrome P450 (CYP) enzymes, CYP3A4, is responsible for the metabolism of a wide variety of xenobiotics, including an estimated 60% of all clinically used drugs. In this study, we investigated the effect of Ban-Lan-Gen on the transcriptional activation of the CYP3A4 gene. Ban-Lan-Gen extract increased CYP3A4 gene reporter activity in a dose-dependent manner. Indirubin, one of the biologically active ingredients in the Ban-Lan-Gen, also dose-dependently increased CYP3A4 gene reporter activity. Expression of short hairpin RNA for the human pregnane X receptor (hPXR-shRNA) inhibited CYP3A4 gene reporter activity, and overexpression of human PXR increased indirubin- and rifampicin-induced CYP3A4 gene reporter activity. Furthermore, indirubin induced CYP3A4 mRNA expression in HepG2 cells. Taken together, these results indicate that indirubin, a component of Ban-Lan-Gen, activated CYP3A4 gene transcription through the activation of the human PXR. Copyright (C) 2016, Published by Elsevier Ltd on behalf of The Japanese Society for the Study of Xenobiotics.
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