Induction of NAD(P)H:Quinone Reductase by Rutaecarpine Isolated from the Fruits of Evodia rutaecarpa in the Murine Hepatic Hepa-1c1c7 Cell Line

Rutaecarpine is a quinazolinocarboline alkaloid isolated from Evodia rutaecarpa (Juss.), which has been used in traditional Chinese medicine. The bioactivity-guided fractionation has led to the isolation of rutaecarpine from the extract of the fruits of E. rutaecarpa as the major component possessing NAD(P)H:quinone reductase (QR) activity. The activator protein-1 (AP-1), a transcriptional factor, in the antioxidant response element (ARE) region plays an important role in mediating induction of the target genes by xenobiotics, including chemopreventive agents. The present study demonstrates that rutaecarpine induces QR activity and gene expression by transactivation of AP-1. To study the induction of QR activity and AP-1-mediated QR gene expression by rutaecarpine, we performed enzyme and reporter gene assays. This compound markedly induced the enzyme activity and mRNA expression levels of QR in a dose-dependent manner. Using the luciferase reporter gene assay, a dose-dependent transactivation of AP-1-mediated luciferase expression was observed upon treatment of rutaecarpine. These results suggest that rutaecarpine induces QR gene expression and activity through an increase in AP-1 activation.