title: Tanshinone I increases CYP1A2 protein expression and enzyme activity in primary rat hepatocytes.
abstract: This study investigated the effects of Danshen and its active ingredients on the protein expression and enzymatic activity of CYP1A2 in primary rat hepatocytes. The ethanolic extract of Danshen roots (containing mainly tanshinones) inhibited CYP1A2-catalyzed phenacetin O-deethylation (IC(50)=24.6 μg/ml) in primary rat hepatocytes while the water extract containing mainly salvianolic acid B and danshenshu had no effect. Individual tanshinones such as cryptotanshinone, dihydrotanshinone, tanshinone IIA inhibited the CYP1A2-mediated metabolism with IC(50) values at 12.9, 17.4 and 31.9 μM, respectively. After 4-day treatment of the rat hepatocytes, the ethanolic extract of Danshen and tanshinone I increased rat CYP1A2 activity by 6.8- and 5.2-fold, respectively, with a concomitant up-regulation of CYP1A2 protein level by 13.5- and 6.5-fold, respectively. CYP1A2 induction correlated with the up-regulation of mRNA level of aryl hydrocarbon receptor (AhR), which suggested a positive feedback mechanism of tanshinone I-mediated CYP1A2 induction. A formulated Danshen pill (containing mainly danshensu and salvianolic acid B and the tanshinones) up-regulated CYP1A2 protein expression and enzyme activity, but danshensu and salvianolic acid B, when used individually, did not affect CYP1A2 activity. This study was the first report on the Janus action of the tanshinones on rat CYP1A2 activity.
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
authors: Wayne Y W
authors: WY
authors: Lee
authors: Xuelin
authors: X
authors: Zhou
authors: Penelope M Y
authors: PM
authors: Or
authors: Yiu Wa
authors: YW
authors: Kwan
authors: John H K
authors: JH
authors: Yeung
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D002470:Cell Survival; D019388:Cytochrome P-450 CYP1A2; D003580:Cytochromes / Q000235:genetics / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004789:Enzyme Activation; D004790:Enzyme Induction; D000431:Ethanol / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010615:Phenacetin / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon; D027561:Salvia miltiorrhiza; D013619:Tacrine / Q000494:pharmacology; D053630:Depsides
chemical_list: D045784:Abietanes; D001572:Benzofurans; D019388:Cytochrome P-450 CYP1A2; D003580:Cytochromes; D004365:Drugs, Chinese Herbal; D000431:Ethanol; D010615:Phenacetin; D010616:Phenanthrenes; D010618:Phenanthrolines; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D013619:Tacrine; C021751:tanshinone; C028972:dan-shen root extract; C037886:cryptotanshinone; C076944:salvianolic acid B; D053630:Depsides; C017170:Cyp1a2 protein, rat