Effect of strychnine hydrochloride on liver cytochrome P450 mRNA expression and monooxygenase activities in rat

Strychnos nux-vomica L. has been frequently used in traditional Chinese medicine but has high acute toxicity. It is commonly taken with Glycyrrhizae radix to decrease its toxicity but the mechanism of this interaction is unknown. In this work, the mRNA expression and the activity of four cytochrome P450 (CYP) enzymes representative of four subfamilies (CYP1A, CYP3A, CYP2C and CYP2E) were determined ex vivo in rat livers from groups of Wistar rats orally administered strychnine hydrochloride (SH) at three doses (0.1, 0.3 and 0.9 mg/kg/day) alone and, at the highest dose, in combination with glycyrrhetinic acid (GA, 25 mg/kg/day) or liquiritin (LQ, 20 mg/kg/day) once a day for 7 consecutive days. Compared to control, the mRNA expressions of CYP3A1, 1A2 and 2E1 were higher in rats receiving the highest dose of SH but lower for CYP3A1 and CYP2E1 in rats receiving the SH+GA and SH+LQ combinations. CYP2E1 activity was higher and CYP2C, CYP3A and CYP1A2 activities were lower in rats receiving the highest dose of SH. In contrast CYP1A2 and CYP2C activities were higher and CYP2E1 and CYP3A activities lower in rats receiving the SH+GA combination. CYP2E1 and CYP3A activities were also lower in rats receiving the SH+LQ combination. The results show that treatment with SH for 7 days affects the expression and the activity of CYP enzymes and that coadministration of GA and LQ modulates these effects. This modulation may explain the role of Glycyrrhizae radix in reducing the acute toxicity of Strychnos nux-vomica L.CYPs enzymes.

Graphical abstractmRNA expression and activity of four cytochrome P450 (CYP) enzymes were determined ex vivo in rat livers from groups of Wistar rats orally administered strychnine hydrochloride (SH) at three doses alone and in combination with glycyrrhetinic acid (GA, 25 mg/kg/day) or liquiritin (LQ, 20 mg/kg/day).Figure optionsDownload full-size imageDownload as PowerPoint slide