Effects of liquorice on pharmacokinetics of aconitine in rats.

1. Aconite alkaloids are the main bioactive ingredients existing in aconitum, for instance aconitine, which exhibit potent analgesic, antirheumatic and other pharmacological effects. In this study, effects of long-term treatment with liquorice on pharmacokinetics of aconitine in rats were investigated. 2. Pharmacokinetics of aconitine after oral administration of aconitine at 1.5 mg/kg either with pretreatment of liquorice water extract at 0.433 g/kg or 1.299 g/kg (crude drug) respectively for one week or not were studied. Additionally, LS-180 cells and human primary hepatocytes were utilized to explore the potential effects of bioactive ingredients of liquorice on P-gp and CYPs, respectively. 3. The results revealed that exposure of aconitine after pretreatment with liquorice was altered remarkably. AUC decreased from 161 ± 37.8 to 58.8 ± 8.97 and 44.7 ± 8.20 ng/ml*h, respectively. Similarly, Cmax decreased from 26.2 ± 5.19 to 11.8 ± 1.15 and 6.86 ± 0.600 ng/ml, respectively. In addition, expressions of CYPs of human primary hepatocytes were enhanced to various contents after induction. Moreover, accumulation of aconitine and hypaconitine, not mesaconitine inside of LS-180 cells were reduced after pretreatment by comparison with control. 4. In conclusion, the exposure of aconitine in vivo declined after pretreatment with liquorice extract, which may be highly associated with upregulated expression and/or function of CYPs and P-gp.