Indirubin, a component of Ban-Lan-Gen, activates CYP3A4 gene transcription through the human pregnane X receptor

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• 作者：Takeshi Kumagai^a ; ^{ta-kuma@tohoku-pharm.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Yusuke Aratsu^a ; ^b ; Ryosuke Sugawara^a ; Takamitsu Sasaki^a ; ^c ; Shinichi Miyairi^d ; Kiyoshi Nagata^a
• 关键词：AhR activator ; Indirubin ; CYP3A4 induction ; PXR ; Herb&ndash ; drug interactions
• 刊名：Drug Metabolism and Pharmacokinetics
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：31
• 期：2
• 页码：139-145
• 全文大小：776 K

文摘

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.