Role of P-glycoprotein in the Transport of Tanshinone I, One Active Triterpenoid from Salvia miltiorrhiza
The extracts from the root of Salvia miltiorrhiza are widely used in the treatment of angina and stroke. In this study, we have investigated the role of P-glycoprotein (P-gp) in the transport of tanshinone I (TSI), a major active constituent of S. miltiorrhiza. The TSI transport across Caco-2 monolayers was pH-, energy-, and temperature-dependent, but not sodium-dependent. TSI exhibited a polarized transport in Caco-2 monolayers which was attenuated by P-gp inhibitors. The permeability (Papp) values of TSI in the basolateral to apical direction were significantly higher in MDCK-II cells over-expressing MDR1, as compared to the wild-type control cells. Furthermore, TSI significantly inhibited the transport of digoxin in Caco-2 cells with an IC50 value of 0.53 ± 0.09 μM. TSI also moderately stimulated P-gp ATPase activity with Km and Vmax values of 31.70 ± 7.09 μM and 57.71 ± 5.26 nmol/min/mg protein, respectively. Our findings indicate that TSI is a substrate and inhibitor of Pgp, which has important clinical and toxicological implications.
No Supplementary Data
No Article Media
Document Type: Research Article
Publication date: August 1, 2008
More about this publication?
- Drug Metabolism Letters publishes short papers on major advances in all areas of drug metabolism and disposition. The emphasis will be on publishing quality papers very rapidly. Letters will be processed rapidly by taking full advantage of the Internet technology for both the submission and review of manuscripts. The journal covers the following areas:
In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites, reactive intermediate and glutathione conjugates.
- Editorial Board
- Information for Authors
- Subscribe to this Title
- Ingenta Connect is not responsible for the content or availability of external websites