Abstract
The potential for herb-drug interactions has recently received greater attention worldwide, considering the fact that the use of herbal products becomes more and more widespread. The goal of this work was to examine the potential for the metabolism-based drug interaction arising from seven active components (danshensu, protocatechuic aldehyde, protocatechuic acid, salvianolic acid B, tanshinone I, tanshinone IIA, and cryptotanshinone) of danshen extract. Probe substrates of cytochrome P450 enzymes were incubated in human liver microsomes (HLMs) with or without each component of danshen extract. IC50 and Ki values were estimated, and the types of inhibition were determined. Among the seven components of danshen extract, tanshinone I, tanshinone IIA, and cryptotanshinone were potent competitive inhibitors of CYP1A2 (Ki = 0.48, 1.0, and 0.45 μM, respectively); danshensu was a competitive inhibitor of CYP2C9 (Ki = 35 μM), and cryptotanshinone was a moderate mixed-type inhibitor of CYP2C9 (Ki = 8 μM); cryptotanshinone inhibited weakly and in mixed mode against CYP2D6 activity (Ki = 68 μM), and tanshinone I was a weak inhibitor of CYP2D6 (IC50 = 120 μM); and protocatechuic aldehyde was a weak inhibitor of CYP3A4 (IC50 = 130 and 160 μM for midazolam and testosterone, respectively). These findings provided some useful information for safe and effective use of danshen preparations in clinical practice. Our data indicated that it was necessary to study the in vivo interactions between drugs and pharmaceuticals with danshen extract.
Footnotes
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This study was supported by the Education Bureau of Anhui Province, China (Grant KJ2007B210), by the National Natural Science Foundation of the People's Republic of China (Grants 30572228 and 30630076), and by supporting programs from the Ministry of Science and Technology of the People's Republic of China in the 11th 5-Year Plan (2006BAI081304-05).
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F.Q. and R.Z. contributed equally to this work.
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.108.021030.
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ABBREVIATIONS: P450, cytochrome P450; HLM, human liver microsome; HPLC, high-performance liquid chromatography; ESI, electrospray ionization.
- Received February 13, 2008.
- Accepted April 8, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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