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Evidence-Based Complementary and Alternative Medicine
Volume 2012, Article ID 872458, 8 pages
Research Article

Active Hydrophilic Components of the Medicinal Herb Salvia miltiorrhiza (Danshen) Potently Inhibit Organic Anion Transporters 1 (Slc22a6) and 3 (Slc22a8)

Department of Pharmaceutics, Virginia Commonwealth University, 410 N 12th Street, Richmond, VA 23298, USA

Received 19 April 2012; Revised 25 May 2012; Accepted 31 May 2012

Academic Editor: Youn Chul Kim

Copyright © 2012 Li Wang and Douglas H. Sweet. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Many active components of herbal products are small organic anions, and organic anion transporters were previously demonstrated to be a potential site of drug-drug interactions. In this study, we assessed the inhibitory effects of six hydrophilic components of the herbal medicine Danshen, lithospermic acid, protocatechuic acid, rosmarinic acid, salvianolic acid A, salvianolic acid B, and tanshinol, on the function of the murine organic anion transporters, mOat1 and mOat3. All of Danshen components significantly inhibited mOat1- and mOat3-mediated substrate uptake ( 𝑃 < 0 . 0 0 1 ) with lithospermic acid (LSA), protocatechuic acid, rosmarinic acid (RMA), and salvianolic acid A (SAA) producing virtually complete inhibition under test conditions. Kinetic analysis demonstrated that LSA, RMA, and SAA were competitive inhibitors. As such, 𝐾 𝑖 values were estimated as 1 4 . 9 Β± 4 . 9 μM for LSA, 5 . 5 Β± 2 . 2 μM for RMA, and 4 . 9 Β± 2 . 2 μM for SAA on mOat1-mediated transport, and as 3 1 . 1 Β± 7 . 0 μM for LSA, 4 . 3 Β± 0 . 2 μM for RMA, and 2 1 . 3 Β± 7 . 7 μM for SAA on mOat3-mediated transport. These data suggest that herb-drug interactions may occur in vivo on the human orthologs of these transporters in situations of polypharmacy involving Danshen and clinical therapeutics known to be organic anion transporter substrates.