Indirubin, a component of Ban-Lan-Gen, activates CYP3A4 gene transcription through the human pregnane X receptor. Issue 2 (April 2016)

• Record Type: Journal Article
• Authors: Kumagai, Takeshi; Aratsu, Yusuke; Sugawara, Ryosuke; Sasaki, Takamitsu; Miyairi, Shinichi; Nagata, Kiyoshi
• Is Part Of: Drug metabolism and pharmacokinetics. Volume 31:Issue 2(2016)
• Page Start: 139
• Page End: 145
• Publication Date: 2016-04
• Subjects: AhR activator -- Indirubin -- CYP3A4 induction -- PXR -- Herb–drug interactions; AdCont β-galactosidase-expressing adenovirus -- AdPXR human PXR-expressing adenovirus -- AdhPXR-shRNA AdhPXR-short hairpin RNA -- AhR aryl hydrocarbon receptor -- Ct threshold PCR cycle -- CAR constitutive androstane receptor -- CYP cytochrome P450 -- DMEM Dulbecco's modified Eagle's medium -- dNR1 distal nuclear receptor-binding protein 1 -- DMSO dimethyl sulfoxide -- D-PBS Dulbecco's phosphate buffered saline -- DR3 direct repeats spaced by 3 bases -- eNR3A4 essential distal nuclear receptor-binding element -- ER6 everted repeats separated by 6 bases -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- GBE Ginkgo biloba extract -- GRα glucocorticoid receptor-α -- MOI multiplicity of infection -- PAHs polycyclic aromatic hydrocarbons -- prER6 ER6 in the CYP3A4 proximal promoter -- PXR pregnane X receptor -- RXRα retinoid X receptor α -- SJW St. John's wort -- TCID50 50% titer culture infectious dose -- VDR vitamin D receptor; Drugs -- Metabolism -- Periodicals; Pharmacokinetics -- Periodicals; 615.7
• DOI: 10.1016/j.dmpk.2016.01.002
• Languages: English
• ISSNs: 1347-4367

Abstract

Abstract: 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.