Effects of liquorice on pharmacokinetics of aconitine in rats

Abstract

1. Aconite alkaloids are the main bioactive ingredients existing in Aconitum, for instance aconitine (AC), which exhibit potent analgesic, antirheumatic and other pharmacological effects. In this study, effects of long-term treatment with liquorice on pharmacokinetics of AC in rats were investigated.

2. Pharmacokinetics of AC after oral administration of AC at 1.5 mg/kg either with pre-treatment of liquorice water extracts at 0.433 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-glycoprotein (P-gp) and Cytochromes P450 (CYPs), respectively.

3. The results revealed that exposure of AC after pre-treatment with liquorice was altered remarkably. Area under the concentration-time curve (AUC) decreased from 161 ± 37.8 to 58.8 ± 8.97 and 44.7 ± 8.20 ng/mL*h, respectively. Similarly, C_max 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 AC and hypaconitine (HA), not mesaconitine (MA) inside of LS-180 cells were reduced after pre-treatment by comparison with control.

4. In conclusion, the exposure of AC in vivo declined after pre-treatment with liquorice extract, which may be highly associated with upregulated expression and/or function of CYPs and P-gp.

Keywords:

• Liquorice
• aconite
• efflux transporter
• P450 enzyme
• pharmacokinetics

Acknowledgements

The authors are also very grateful for Mr. Chuan LI and Dr. Haizhi ZHANG for their technical assistance and helpful discussion.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by National Key Research and Development Program [Grant 2016YFE0121400], National Natural and Science Foundation [Grant No. 81430096], Macau Science and Technology Development Fund [006/2015/AMJ to Y.Xie], the Programme of Changjiang Scholars and Innovative Research Team in University [No.IRT_14R41] and Tianjin Natural and Science Foundation [No. 17YFZCSY01170].