Salvianolic acid B as a substrate and weak catechol-O-methyltransferase inhibitor in rats.


1. The aim of this study was to investigate the biotransformation of salvianolic acid B (SAB) by catechol-O-methyltransferase (COMT) and its interaction with levodopa (l-DOPA) methylation in rats. 2. The enzyme kinetics of SAB were studied after incubation with rat COMT. The in vivo SAB and 3-monomethyl-SAB (3-MMS) levels were determined after a single dose of tolcapone with or without SAB administration. For l-DOPA, the effect of SAB inhibition on l-DOPA methylation was studied in vitro. The l-DOPA and 3-O-methyldopa (3-OMD) levels were determined after single and multiple doses of SAB with or without l-DOPA administration. 3. After incubation, we found that SAB was methylated mainly by rat liver and kidney COMT. Tolcapone strongly inhibited the formation of 3-MMS in vitro and in vivo, without any change in the plasma concentration of SAB. Moreover, tolcapone significantly increased the cumulative bile excretion of SAB from 3% to 40% in the rat. SAB inhibited the methylation of l-DOPA with an IC50 value of 2.08 μM in vitro. In vivo, a single intravenous dose of SAB decreased the plasma concentration of 3-OMD, with no obvious effect on the pharmacokinetics of l-DOPA. Multiple doses of SAB given to rats also decreased the plasma concentration of 3-OMD, while SAB increased the plasma concentration of l-DOPA.

DOI: 10.3109/00498254.2015.1017753

Cite this paper

@article{Qi2015SalvianolicAB, title={Salvianolic acid B as a substrate and weak catechol-O-methyltransferase inhibitor in rats.}, author={Qu Qi and Lijuan Cao and Feiyan Li and Hong Wang and Huiying Liu and Haiping Hao and Kun Hao}, journal={Xenobiotica; the fate of foreign compounds in biological systems}, year={2015}, volume={45 9}, pages={820-7} }