Peganum harmala L. is a candidate herbal plant for preventing dioxin mediated effects

Dioxins are widespread environmental contaminants that have been linked with a variety of deleterious effects on human health including increased cancer rates. The detrimental effects of 2,3,7,8-tetrachlorodibenzo- P-dioxin (TCDD, one of the most common environmental dioxins) are mediated via the aryl hydrocarbon receptor (AhR). AhR is a transcription factor that regulates the expression of the carcinogen-activating enzyme, cytochrome P450 1a1 (Cyp1a1). In the present study, we examined the ability of the methanolic extract of Peganum harmala L. (Zygophyllaceae) fruiting tops to affect TCDD-activated AhR-mediated signal transduction in mouse hepatoma Hepa 1c1c7 cells. Our results showed that Peganum harmala extract significantly inhibited the TCDD-mediated induction of Cyp1a1 at mRNA, protein, and activity levels. A similar pattern of inhibition at the catalytic activity level was observed with the other AhR ligands tested. The ability of the extract to inhibit Cyp1a1 was strongly correlated with its ability to inhibit AhR-dependent luciferase activity and electrophoretic mobility shift assays. Harmine and harmaline were found to be the dominant components of the plant extract with a relative abundance of 7 and 4.85 % (w/w), respectively. In addition, both of the active alkaloids showed an inhibitory effect on TCDD-induced Cyp1a1 activity level. We concluded that Peganum harmala L. can interfere with AhR ligands-mediated effects.