Root extract of water dropwort, Oenanthe javanica (Blume) DC, induces protein and gene expression of phase I carcinogen-metabolizing enzymes in HepG2 cells

Abstract

Background: Cytochrome P450 (CYP) isoenzymes are an important phase I enzyme system. In the present study, we investigated the effects of Oenanthe javanica (Blume) DC on CYP1A1 and CYP1A2. Findings: Whole plants were completely dried and then divided into leaves, stems, and roots for extraction. The human liver hepatocellular carcinoma cell line HepG2 was treated with ethanol extracts of these organs for 72 h and mRNA and protein expression levels were assessed. The root extract of O. javanica significantly elevated the expression of both CYP1A1 and CYP1A2 mRNAs (by 68 and 102 %, respectively). Similarly, the CYP1A1 and CYP1A2 protein levels were increased by the root extract (by 112 and 157 %, respectively). The effects of the root extract were much more pronounced than those of leaf and stem extracts. Subsequent GC-MS analysis revealed that the levels of major coumarin derivatives, xanthotoxin, bergapten, and isopimpinellin, were significantly higher in O. javanica root extracts than in leaf or stem extracts. Of note, 5 mu M xanthotoxin (the most abundant furanocoumarin in O. javanica) induced the expression of CYP1A1 mRNA as well as CYP1A2 mRNA and protein, albeit the CYP1A1 protein level was elevated only at 10 mu M xanthotoxin. Conclusions: Although it is difficult to extrapolate such effects to metabolic outcomes because of the inherent limitations of in vitro experiments, it is important to note that dietary exposure to O. javanica may modulate phase I enzymes and thereby affect various xenobiotic metabolism.