RT Journal Article
SR Electronic
T1 Inhibitory Effects of Seven Components of Danshen Extract on Catalytic Activity of Cytochrome P450 Enzyme in Human Liver Microsomes
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1308
OP 1314
DO 10.1124/dmd.108.021030
VO 36
IS 7
A1 Furong Qiu
A1 Rong Zhang
A1 Jianguo Sun
A1 Jiye A
A1 Haiping Hao
A1 Ying Peng
A1 Hua Ai
A1 Guangji Wang
YR 2008
UL http://dmd.aspetjournals.org/content/36/7/1308.abstract
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