Abstract
Salvia miltiorrhiza root (Danshen) is widely used in Asia for its cardiovascular benefits and contains both hydrophilic phenolic acids and lipophilic tanshinones, which are believed to be responsible for its therapeutic efficacy. This review summarized the effects of these bioactive components from S. miltiorrhiza roots on pharmacokinetics of comedicated drugs with mechanic insights regarding alterations of protein binding, enzyme activity, and transporter activity based on the published data stemming from both in vitro and in vivo human studies. In vitro studies indicated that cytochrome P450 (CYP450), carboxylesterase enzyme, catechol-O-methyltransferase, organic anion transporter 1 (OAT1) and OAT3, and P-glycoprotein were the major targets involved in S. miltiorrhiza-drug interactions. Lipophilic tanshinones had much more potent inhibitory effects towards CYPs activities compared to hydrophilic phenolic acids, evidenced by much lower Ki values of the former. Clinical S. miltiorrhiza-drug interaction studies were mainly conducted using CYP1A2 and CYP3A4 probe substrates. In addition, the effects of coexisting components on the pharmacokinetic behaviors of those noted bioactive compounds were also included herein.
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