title: Investigation of cytochrome P450 1A2 and 3A inhibitory properties of Danshen tincture.
abstract: Danshen (Salvia miltiorrhiza Bunge) as a famous Traditional Chinese medicine is widely used in the treatment of cardiovascular and cerebrovascular diseases in the world. Danshen tincture (DT), extracted from Danshen root with a mixture of water and alcohol, is a commonly used preparation method for human consumption. The aim of this study was to investigate the effects of DT on the cytochrome P450 (CYP) 1A2 and 3A activities by human and rat liver microsomes. Effects of DT were assessed with use of Danshen ethanolic extract (DEE) and selective substrates, markers of CYP activities. DEE (0.5-10 μg/ml) competitively inhibited human and rat liver microsomal CYP1A2 activity with inhibition constant (K(i)) values at 3.40 and 5.16 μg/ml, respectively. At the same time, DEE (2.5-20 μg/ml) not only noncompetitively inhibited human liver microsomal CYP3A4/5 activity with a K(i) of 11.9 μg/ml, but also competitively inhibited rat liver microsomal CYP3A1/2 activity with a K(i) of 52.1 μg/ml. The data indicate that DEE inhibited the metabolism of CYP1A2 and 3A substrates in human and rat liver in vitro with different mode of inhibition. This study may be helpful for clinical application of Danshen tincture.
authors: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China. usxinwang@gmail.com
authors: Xin
authors: X
authors: Wang
authors: John Hok-Keung
authors: JH
authors: Yeung
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000737:chemistry; D041743:Herb-Drug Interactions; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010615:Phenacetin / Q000494:pharmacology; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D013739:Testosterone / Q000494:pharmacology; D014867:Water / Q000737:chemistry
chemical_list: D015415:Biomarkers; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065692:Cytochrome P-450 CYP3A Inhibitors; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D010618:Phenanthrolines; D014867:Water; C028972:dan-shen root extract; D000431:Ethanol; D013739:Testosterone; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D010615:Phenacetin