title: Inhibitory effects of seven components of danshen extract on catalytic activity of cytochrome P450 enzyme in human liver microsomes.
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. IC(50) and K(i) 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 (K(i) = 0.48, 1.0, and 0.45 microM, respectively); danshensu was a competitive inhibitor of CYP2C9 (K(i) = 35 microM), and cryptotanshinone was a moderate mixed-type inhibitor of CYP2C9 (K(i) = 8 microM); cryptotanshinone inhibited weakly and in mixed mode against CYP2D6 activity (K(i) = 68 microM), and tanshinone I was a weak inhibitor of CYP2D6 (IC(50) = 120 microM); and protocatechuic aldehyde was a weak inhibitor of CYP3A4 (IC(50) = 130 and 160 microM 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.
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu 210038, China.
authors.forename: Furong
authors.initials: F
authors.lastname: Qiu
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Sun
authors.forename: A
authors.initials: A
authors.lastname: Jiye
authors.forename: Haiping
authors.initials: H
authors.lastname: Hao
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.forename: Hua
authors.initials: H
authors.lastname: Ai
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
mesh_terms: D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D027561:Salvia miltiorrhiza
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004365:Drugs, Chinese Herbal; C028972:dan-shen root extract; D003577:Cytochrome P-450 Enzyme System