PT  - JOURNAL ARTICLE
AU  - Furong Qiu
AU  - Rong Zhang
AU  - Jianguo Sun
AU  - Jiye A
AU  - Haiping Hao
AU  - Ying Peng
AU  - Hua Ai
AU  - Guangji Wang
TI  - Inhibitory Effects of Seven Components of Danshen Extract on Catalytic Activity of Cytochrome P450 Enzyme in Human Liver Microsomes
AID  - 10.1124/dmd.108.021030
DP  - 2008 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 1308--1314
VI  - 36
IP  - 7
4099  - http://dmd.aspetjournals.org/content/36/7/1308.short
4100  - http://dmd.aspetjournals.org/content/36/7/1308.full
SO  - Drug Metab Dispos2008 Jul 01; 36
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics