active hydrophilic components of the medicinal herb salvia miltiorrhiza (danshen) potently inhibit organic anion transporters 1 (slc22a6) and 3 (slc22a8)主动亲水成分的草药丹参(丹参)强有力地抑制有机阴离子转运蛋白1(slc22a6)和3(slc22a8).pdfVIP

Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2012, Article ID 872458, 8 pages doi:10.1155/2012/872458 Research Article Active Hydrophilic Components of the Medicinal Herb Salvia miltiorrhiza (Danshen) Potently Inhibit Organic Anion Transporters 1 (Slc22a6) and 3 (Slc22a8) Li Wang and Douglas H. Sweet Department of Pharmaceutics, Virginia Commonwealth University, 410 N 12th Street, Richmond, VA 23298, USA Correspondence should be addressed to Douglas H. Sweet, dsweet@ Received 19 April 2012; Revised 25 May 2012; Accepted 31 May 2012 Academic Editor: Youn Chul Kim Copyright © 2012 L. Wang and D. 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 0.001) 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, Ki values were estimated as 14.9 ± 4.9 μM for LSA, 5.5